Pharmacology – ClinCaseQuest https://clincasequest.hospital Medical education in clinical cases Sun, 22 Sep 2024 11:54:19 +0000 en-US hourly 1 https://wordpress.org/?v=6.2.11 https://clincasequest.hospital/wp-content/uploads/sites/7/2020/02/logo-ru-project-90x90.png Pharmacology – ClinCaseQuest https://clincasequest.hospital 32 32 Karnofsky Performance Status Scale Online Calculator https://clincasequest.hospital/karnofsky-performance-status-scale/ Mon, 29 Aug 2022 07:21:53 +0000 https://clincasequest.hospital/?p=34206 Karnofsky performance status scale determines ability of patient to tolerate chemotherapy. For patients ≥ 16 years old. Useful to use over time to track disease…

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]]> Karnofsky performance status scale determines ability of patient to tolerate chemotherapy.

For patients ≥ 16 years old.

Useful to use over time to track disease progression.

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The Karnofsky Performance Status Scale (KPS)  is widely used for a variety of purposes, including response to chemotherapy for cancer and assessment of chronic disease. This scale can be used to assess patients with advanced cancer or other chronic diseases, as well as progressive debility in the elderly.

The Karnofsky Performance Status Scale quantifies a patient’s functional ability and the effect of treatment, such as chemotherapy, on their basic functional ability. It is sometimes also used for prognostic purposes and to guide treatment.

The score on the scale is highly correlated with survival time and need for home care. It can also help predict the ability to progress with invasive and intensive treatments.

Patient Description  Points*Result
Normal no complaints; no evidence of disease  100Able to carry on normal activity and to work; no special care needed.
Able to carry on normal activity; minor signs or symptoms of disease  90Able to carry on normal activity and to work; no special care needed.
Normal activity with effort; some signs or symptoms of disease  80Able to carry on normal activity and to work; no special care needed.
Cares for self; unable to carry on normal activity or to do active work  70Unable to work; able to live at home and care for most personal needs; varying amount of assistance needed.
Requires occasional assistance, but is able to care for most of his personal needs  60Unable to work; able to live at home and care for most personal needs; varying amount of assistance needed.
Requires considerable assistance and frequent medical care  50Unable to work; able to live at home and care for most personal needs; varying amount of assistance needed.
Disabled; requires special care and assistance  40Unable to care for self; requires equivalent of institutional or hospital care; disease may be progressing rapidly.
Severely disabled; hospital admission is indicated although death not imminent  30Unable to care for self; requires equivalent of institutional or hospital care; disease may be progressing rapidly.
Very sick; hospital admission necessary; active supportive treatment necessary  20Unable to care for self; requires equivalent of institutional or hospital care; disease may be progressing rapidly.
Moribund; fatal processes progressing rapidly  10Unable to care for self; requires equivalent of institutional or hospital care; disease may be progressing rapidly.
Dead0Dead.
*% Survival correlates with points assigned

The lower the Karnofsky score, the worse the prognosis, which may be due to:

  • Intolerance to therapy
  • Decreased survival rates
ECOG PERFORMANCE STATUSKARNOFSKY PERFORMANCE STATUS
0—Fully active, able to carry on all pre-disease performance without restriction100—Normal, no complaints; no evidence of disease
 90—Able to carry on normal activity; minor signs or symptoms of disease
1—Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work80—Normal activity with effort, some signs or symptoms of disease
 70—Cares for self but unable to carry on normal activity or to do active work
2—Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours60—Requires occasional assistance but is able to care for most of personal needs
 50—Requires considerable assistance and frequent medical care
3—Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours40—Disabled; requires special care and assistance
 30—Severely disabled; hospitalization is indicated although death not imminent
4—Completely disabled; cannot carry on any selfcare; totally confined to bed or chair20—Very ill; hospitalization and active supportive care necessary
 10—Moribund
5—Dead0—Dead

The Karnofsky Performance Status Scale and other performance scales should be used for the holistic assessment of cancer patients, although its accuracy as a prognostic tool in some cases has not yet been sufficiently proven.

The Karnofsky Performance Status Scale is useful to clinicians in daily clinical practice, and this performance scale should be used to improve understanding of a patient’s needs and abilities, and potentially for prediction.

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Literature

  1. Karnofsky DA Burchenal JH. (1949). ‘The Clinical Evaluation of Chemotherapeutic Agents in Cancer.’ In: MacLeod CM (Ed), Evaluation of Chemotherapeutic Agents. Columbia Univ Press. Page 196.
  2. Crooks, V, Waller S, et al. The use of the Karnofsky Performance Scale in determining outcomes and risk in geriatric outpatients. J Gerontol. 1991; 46: M139-M144.
  3. Hollen PJ, Gralla RJ, et al. Measurement of quality of life in patients with lung cancer in multicenter trials of new therapies. Cancer. 1994; 73: 2087-2098.
  4. O’Toole DM, Golden AM. Evaluating cancer patients for rehabilitation potential. West J Med. 1991; 155:384-387.
  5. Schag CC, Heinrich RL, Ganz PA. Karnofsky performance status revisited: Reliability, validity, and guidelines. J Clin Oncology. 1984; 2:187-193.


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Interactive OSCE Checklist – Emergency care of a patient with chest pain – Acute Coronary Syndrome with ST-segment elevation and equivalents

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• Opening the consultation

• Availability of a defibrillator

• Presenting complaint

• History of presenting complaint

• Past medical history

• Drug history

• Physical examination

• Intravenous access

• Registration of a 12-channel ECG

• Express test for the determination of cardiac troponin, myoglobin, creatine phosphokinase-MB, if possible

• Making preliminary diagnosis

• Drug therapy (basic)

• Evaluation of the door-balloon time (the choice of further reperfusion strategy aimed as soon as possible to restore the coronary blood flow in the infarct-dependent artery)

• Call the nearest reperfusion center

• P2Y12 receptor inhibitor prescription depending on the chosen strategy of reperfusion therapy

• Carrying out thrombolytic therapy as needed

• Transportation to the nearest reperfusion center

Total: 0 / 62
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]]> Interactive OSCE Checklist – Counseling a Patient with an increased INR level https://clincasequest.hospital/osce-checklist-patients-counseling-with-increased-inr/ Sat, 12 Feb 2022 03:52:00 +0000 https://clincasequest.hospital/?p=33243 Register on our website right now to have access to more learning materials! Register Subscribe to our pages:

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• Opening the consultation

• Ideas, concerns, complications and expectations

• Analysis of earlier, current INR results, apropriate INR target range and current warfarin dosing

• Analysis of the factors that may affect the increased INR level

• Providing medical care to the patient if necessary

• Bleeding whilst taking warfarin

• How to take warfarin

• Tips for further warfarin dosing according to the analysis of the reasons that led to the INR levels increase

• Lifestyle advice

• Yellow booklets and alert card

• Closing the consultation

• Key communication skills

• Key clinical skills

Total: 0 / 50

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]]> Patient’s counseling with an increased INR level / OSCE guide https://clincasequest.hospital/counseling-a-patient-with-inr-increase-osce-guide/ Mon, 07 Feb 2022 08:12:00 +0000 https://clincasequest.hospital/?p=33067 Join our Simulation Training to gain clinical experience Opening the consultation Ideas, concerns, complications and expectations Ideas Explore what the patient currently understands about increased INR…

Сообщение Patient’s counseling with an increased INR level / OSCE guide появились сначала на ClinCaseQuest.

]]>
  • Opening the consultation
    • Wash your hands and don PPE if appropriate
    • Introduce yourself to the patient including your name and role
    • Confirm the patient’s name and date of birth
    • Explain the reason for the consultation
  • Ideas, concerns, complications and expectations
    • Explore what the patient currently understands about increased INR
    • Ask if the patient has any concerns about warfarin
    • Ask if the patient is bleeding now or before counseling
    • Explore what the patient is hoping to get out of the consultation
  • Analysis of earlier, current INR results, apropriate INR target range and current warfarin dosing
    • Evaluate previous warfarin dosages
    • Evaluate the patient’s earlier INR results
    • Assess the patient’s apropriate INR target range
    • Evaluate the results of the current INR
  • Analysis of the factors that may affect the increased INR level
    • Assess the presence of warfarin taking errors, low patient compliance, the complexity of the warfarin regimen for the patient
    • Assess any changes in the patient’s clinical condition
    • Evaluate any changes in medication
    • Evaluate any changes in lifestyle
    • Evaluate changes in alcohol consumption
  • Providing medical care to the patient if necessary
    • Assess the patient’s bleeding and its severity if necessary
      • In case of active bleeding, provide immediate medical care after taking INR results
    • In the absence of bleeding adjust the dosage of warfarin
  • Bleeding whilst taking warfarin
    • Explain that the main side effect of warfarin is bleeding more easily than normal
    • Explain the common types of ‘less serious bleeding’ and what to do if they experience them
    • Explain the rarer types of ‘serious bleeding’ and what to do if they experience them
  • How to take warfarin
    • Explain that warfarin should be taken at the same time each day
    • Explain the different types of warfarin tablets
    • Explain what the patient should do if they forget a dose
    • Advise the patient to let medical professionals know that they take warfarin when they are being prescribed new medications
    • Advise the patient to let the team managing their anticoagulation know when they start taking a new medication
    • Advise the patient about the importance of effective contraception if taking warfarin (if relevant)
  • Tips for further warfarin dosing according to the analysis of the reasons that led to the INR levels increase
    • Estimate the required duration of administration of a concomitant drug that interacts with warfarin (temporary, chronic) as needed
    • Adjust warfarin dosage as needed
    • Withdraw warfarin if necessary
    • Evaluate the rationality and necessity of co-administration of antiplatelet agents and nonsteroidal anti-inflammatory drugs if necessary
  • Lifestyle advice
    • Advise the patient about the impact of diet on the effect of warfarin
    • Advise the patient about the impact of alcohol on the effect of warfarin
    • Advise the patient about brushing teeth, shaving and dental procedures
  • Yellow booklets and alert card
    • Provide the patient with information about the INR monitoring booklet and patient information booklet
    • Explain the importance of carrying the anticoagulant alert card with them at all times
  • Closing the consultation
    • Summarise the key points back to the patient
    • Ask the patient if they have any questions or concerns that have not been addressed
    • Arrange appropriate follow-up
    • Thank the patient for their time
    • Dispose of PPE appropriately and wash your hands
  • Key communication skills
    • Active listening
    • Summarising
    • Signposting
  • Key clinical skills
    • Determining the target INR level depending on the clinical situation
    • Analysis of the factors that may affect the INR increase
    • Providing medical care to the patient with INR increase
    • Advice to the patient and explanations about lifestyle, diet

    • Join our Simulation Training to gain clinical experience

    Opening the consultation

    1. Wash your hands and don PPE if appropriate
    2. Introduce yourself to the patient including your name and role.
    3. Confirm the patient’s name and date of birth
    4. Explain the reason for the consultation

    Ideas, concerns, complications and expectations

    1. Explore what the patient currently understands about increased INR
    2. Ask if the patient has any concerns about warfarin
    3. Ask if the patient is bleeding now or before counseling
    4. Explore what the patient is hoping to get out of the consultation
    IdeasExplore what the patient currently understands about increased INR“Have you heard of increased INR?”
    “Do you understand the reasons that can cause an INR increase?”
    “Have you ever had an INR increase before? What did cause it early?”
    Concerns   Ask if the patient has any concerns about warfarin“Is there anything that worries you about taking warfarin?”
    ComplicationsAsk if the patient is bleeding now or before counseling“Are you bleeding at this moment, or before counseling?”
    “Have you had periods that are more intense and last longer than usual?”
    “Have you had bleeding that stops for a little longer than usual?
    “Have you had a nosebleed (lasting more than 10 minutes)?”
    “Did you have bleeds from your gums while brushing your teeth?”
    “Have you had bruises that appear for no reason?”
    “Did you have red urine or black feces?”
    “Did you have blood in your vomit or a cough with blood?”
    “Have you had severe headaches, convulsions (seizures), changes in vision, numbness or tingling in your arms or legs, or a feeling of extreme tiredness, weakness, or nausea?”
    “Have you had any bleeding from the cut or injury that doesn’t stop or slow down?”
    Expectations  Explore what the patient is hoping to get out of the consultation“What were you hoping we’d discuss today?”

    Analysis of earlier, current INR results, apropriate INR target range and current warfarin dosing

    1. Analysis of earlier, current INR results, apropriate INR target range and current warfarin dosing
    2. Evaluate previous warfarin dosages
    3. Evaluate the patient’s earlier INR results
    4. Assess the patient’s apropriate INR target range
    5. Evaluate the results of the current INR

    Target INR ranges

    The most common target INR is 2.5. Others are:

    Recurrent VTE (DVT or PE) despite adequate anticoagulation3.5
    CardioversionPre – 3.0 Post – 2.5*
    Mechanical Heart ValvesSee below

    *The 2016 European Society of Cardiology (ESC) guidelines on cardioversion state that patients who have been in AF for longer than 48 hours should start OAC therapy at least 3 weeks before cardioversion and continue for 4 weeks afterward (in those without a need for long-term anticoagulation).

    Atrial fibrillation Anticoagulation is normally offered to patients with a CHADSVASc score ≥ 2 and considered in men with a CHADSVASc score of 1.

    Warfarin is not usually indicated for ischaemic stroke without atrial fibrillation (except in antiphospholipid syndrome), retinal vessel occlusion, peripheral artery thrombosis, coronary artery graft or coronary angioplasty, and stents.

    Cardioversion

    Anticoagulation for 4 weeks before and for 3 months afterward. To minimize cardioversion cancellations due to low INRs on the day of the procedure we recommend a target INR of 3.0 prior to the procedure and 2.5 afterward (Oxford guidelines).

    *The 2016 European Society of Cardiology (ESC) guidelines on cardioversion state that patients who have been in AF for longer than 48 hours should start OAC therapy at least 3 weeks before cardioversion and continue for 4 weeks afterward (in those without a need for long-term anticoagulation).

    Mechanical Heart Valves.  Target INR range based on indications

    Target INR in mechanical heart valve replacement Mechanical Prosthesis thrombogenicity*Isolated Aortic Valve ReplacementMitral or Tricuspid Valve Replacement, or
     No risk factors**AVR with Risk factors **
    Low (most current valves)2.53.0
    Medium3.03.5
    High3.53.5***

    *Prosthesis thrombogenicity:

    • Low: Carbomedics (aortic position), Medtronic Hall, St Jude Medical (without silzone)
    • Medium: Bjork-Shiley, other bileaflet valves
    • High: Starr-Edwards, Omniscience, Lillehei-Kaster.

    **Patient-related risk factors for thrombosis:

    • Mitral, tricuspid or pulmonary position
    • Previous arterial thromboembolism
    • Atrial fibrillation
    • Left atrium diameter >50 mm
    • Mitral stenosis of any degree
    • Left ventricular ejection fraction< 35%.

    ***Was 4.0 in ESC guideline

    Analysis of the factors that may affect the increased INR level

    1. Assess the presence of warfarin taking errors, low patient compliance, the complexity of the warfarin regimen for the patient
    2. Assess any changes in the patient’s clinical condition
    3. Evaluate any changes in medication
    4. Evaluate any changes in lifestyle
    5. Evaluate changes in alcohol consumption

    It is necessary to clarify with the patient what doses he/she has taken in the last two weeks and to review the dosing schedule.
    Ask the patient to bring all their drugs and a box of pills to make sure the drug is correct and the dosage regimen is appropriate.

    COMMON CAUSES OF HIGH INRs

    NON‐COMPLIANCE OR
    ERRORS IN DOSING
    (The patient mistakenly took a different dosage regimen than was prescribed)    		– Complex regimen
    – Splitting tablets
    – Dosing error or duplication
    – Multiple tablet strengths
    DRUG THERAPY CHANGES, DRUG INTERACTIONS– Warfarin dose recently altered
    – Recent antibiotic use
    – OTC or herbal product added, deleted, or dose altered
    – Medication added, deleted, or dose altered
    LIFESTYLE CHANGES, MALNUTRITION (vitamin K deficiency)– Increase in alcohol use or binge drinking;
    – Decrease in consumption of Vitamin K containing foods;
    – Chewing tobacco use recently decreased or discontinued;
    ALTERED HEALTH STATES– Fever, acute illness, diarrhea,
    – Reduced food intake
    – Uncontrolled hyperthyroidism
    – CHF exacerbation
    – Liver disease

    The patient should be asked the following questions to assess the factors that may lead to an INR increase

    NON‐COMPLIANCE OR
    ERRORS IN DOSING    		“Do you have difficulties in taking warfarin?”
    “Do you understand the warfarin dosing regimen that was prescribed for you?”
    “Do you understand the warfarin dosing regimen?”
    “Aren’t you confused about taking warfarin?”
    “Is it difficult to take your recommended warfarin dosage regimen?”
    “What dosages of warfarin have you been taking lately?”
    “Is it convenient for you to divide warfarin tablets in half?”
    “Do you remember the mistakes in taking warfarin?”
    “Can you mention the mistakes in warfarin?”
    “Do you remember days when you took a double dose of warfarin?”
    “Do you remember days when you mistakenly took more warfarin than you were prescribed?”
    “Are you experiencing any inconvenience due to the variety of warfarin dosing regimens?”
    “Do you have difficulties with different warfarin regimens on different days?”
    “Are you confusing about the dosing regimens that you assigned on certain days?”
    “Is it convenient for you to divide warfarin tablets in half?”
    “Do you remember the mistakes in taking warfarin?”
    “Can you mention the mistakes in warfarin?”
    “Do you remember days when you took a double dose of warfarin?”
    “Do you remember days when you mistakenly took more warfarin than you were prescribed?”
    “Are you experiencing any inconvenience due to the variety of warfarin dosing regimens?”
    “Do you have difficulties with different warfarin regimens on different days?”
    “Are you confusing about the dosing regimens that you assigned on certain days?”
    DRUG THERAPY CHANGES, DRUG INTERACTIONS“Have you recently had increasing in your warfarin dosage?”
    “Has there been a recent adjustment of warfarin dosage?”
    “Have you had a recent concomitant use of antibiotics and other drugs?”
    “Have you been prescribed antifungals, sulfamethoxazole and trimethoprim, and other drugs?”
    “Have you had a recent concomitant use of amiodarone?”
    “Have you had a recent concomitant use of paracetamol or combination drugs containing paracetamol?”
    “Have you had an acute respiratory illness that required paracetamol or a combination of paracetamol-containing drugs?”
    “Have you taken drugs to reduce the acidity of gastric juice?”
    “Have you taken heartburn remedies?”
    “Have you taken antidepressants?”
    “Did you take statins or fibrates?”
    “Have you confessed to acarbose or lactulose?”
    “Didn’t you use phenytoin?”
    “Did you have any recent additions, withdrawals, or changes in over-the-counter or herbal dosage regimens?”
    “Have you had any recent additions, withdrawals, or changes in the dosage regimen of concomitant therapy?”
    “Didn’t you take thyroid hormones?”
    Have you been prescribed vitamin E? ”
    “Have you been prescribed painkillers?”
    “Have you been prescribed allopurinol?”
    “Have you been vaccinated?”
    “Have you used tramadol, oxandrolone?”
    LIFESTYLE CHANGES, MALNUTRITION (vitamin K deficiency)“Have you had an increase in alcohol or binge drinking lately?”
    “Have you had a reduction in your intake of foods containing vitamin K?”
    “Has there been a decrease in the consumption of products containing vitamin K, such as pickles (fennel), mayonnaise, soybean oil, broccoli, Brussels sprouts, cabbage, leafy greens, kale, lettuce, parsley, spinach, watercress (raw)? »
    “Have you used cranberries (eg juice, supplements)?”
    “Did you drink grapefruit or grapefruit juice?”
    “Has your chewing tobacco consumption decreased or stopped lately?”
    ALTERED HEALTH STATES “Have you had a fever lately?”
    “Have you had an acute illness lately?”
    “Have you had diarrhea recently?”
    “Have you had a reduction in food intake?”
    “Do you suffer from hyperthyroidism? Are you receiving treatment for hyperthyroidism? Do you see an endocrinologist about this? Do you monitor your thyroid function? ”
    “Has your condition been deteriorating lately?”
    “Do you have liver disease?”
    “Has your shortness of breath gotten worse?”
    “Has your exercise tolerance decreased in recent times?”
    “Did your lower extremities swell?”
    “Have you had a feeling of shortness of breath lately?”
    “Do you need to sit down at night due to lack of air?”

    Hyperthyroidism and fever

    Both hyperthyroidism and fever result in a hypermetabolic state, which may accelerate the clearance of vitamin K-dependent clotting factors. Thus the amount of warfarin required to produce an anticoagulant effect would decrease. This means when a patient starts to take carbimazole or propylthiouracil to correct their thyroid function, their warfarin requirement will increase as their thyroid function normalizes.

    Liver disease

    The use of warfarin in patients with severe liver disease is contraindicated due to the unpredictable effects of liver disease on coagulation, such as:

    • vitamin K deficiency due to intra- or extra-hepatic cholestasis
    • reduced synthesis of coagulation factors due to severe hepatocellular damage
    • functional abnormalities of platelets and fibrinogen found in many patients with

    Congestive heart failure

    Heart failure can cause hepatic congestion of blood flow and inhibit the metabolism of warfarin leading to excessive anticoagulation with a risk of bleeding. This can be troublesome in patients with frequent exacerbations of heart failure (ie, worsening of heart failure, usually requiring hospitalization).

    Providing medical care to the patient if necessary

    1. Assess the patient’s bleeding and its severity if necessary
    2. In case of active bleeding, provide immediate medical care after taking INR results
    3. In the absence of bleeding adjust the dosage of warfarin

    Criteria for assessing the severity of bleeding (American College of Cardiology, 2020):

    • destabilization of hemodynamics (SBP <90 mm Hg; decrease in SBP ˃40 mm Hg; drop in SBP ≥20 mm Hg or BP ≥10 mm Hg when moving to vertical position; diuresis <0.5 ml/kg/h);
    • bleeding in the critical area (intracranial hemorrhage – intracerebral, subdural, epidural, subarachnoid; other hemorrhages of the central nervous system – intraocular, interracial and extra-axial spinal hemorrhage; hemo tamponade; hemothorax, intra-abdominal and extra-abdominal hemorrhage; pulmonary hemorrhage, posterior epistaxis; intramuscular and intra-articular bleeding);
    • clinically significant bleeding with a decrease in hemoglobin ≥2 g/dl (20 g/l) or requiring transfusion of ≥2 packets of erythrocyte mass.

    If at least one of the above criteria is present, the bleeding is assessed as severe.

    Algorithm for managing a patient with severe bleeding

    Algorithm for managing a patient with minor bleeding

    According to the recommendations of the European Society of Cardiology (2020), there is mild, moderate, and life-threatening bleeding. Further tactics of the patient depend on the severity of bleeding and the type of oral anticoagulant.

    Algorithm for managing a patient with bleeding with VKA

    Vitamin K is a specific antidote to vitamin K antagonists (warfarin and other coumarins), the drug has a dose-dependent effect, administered orally, intravenously at a dose of 1 to 10 mg. Slow intravenous infusion shows a more controlled and rapid effect (significant reduction in INR occurs within 4-6 hours) compared to other routes of administration.
    In the case of severe bleeding in a patient taking VKA, preference is given to a 4-factor concentrate of prothrombin complex, but not to vitamin K.

    Vitamin K1 is an effective antidote to the anticoagulant effect of warfarin. Despite this, data are lacking to show that its use improves outcomes in life-threatening bleeds. While intravenous or oral routes of administration can be used and are effective in reversing an INR that is raised because of warfarin therapy, the intravenous route achieves a more rapid response compared with oral administration, with an onset of action seen within 6–8 hours. However, both routes achieve a similar correction of INR by 24 hours.

    Vitamin K1 should not be administered by subcutaneous or intramuscular routes.

    Subcutaneous administration is no more effective than placebo, while intramuscular injection in an over-anticoagulated patient may lead to hematoma and bleeding, and its effect on reversal is unpredictable owing to variable absorption – it can be associated with a prolonged increase of vitamin K1 plasma levels, which may hinder re-anticoagulation. The major concern about intravenous vitamin K1 has been anaphylaxis. Although the absolute incidence is unknown, it is most likely rare. There is no convincing association between anaphylaxis and dose, concentration, or rate of administration of vitamin K1 but the literature suggests that current formulations with mixed micelles of lecithin and glycol are safer than the previous preparations containing polyethylene castor oil.

    The 4-factor concentrate of the prothrombin complex contains 4 coagulation factors – II, VII, IX, X, as well as protein C and protein S. The required dose of concentrate depends on the level of INR and bodyweight of the patient: at INR 2-4 – 25 IU/kg is recommended; at INR 4-6 – 35 IU/kg is recommended; at INR> 6 – 50 IU/kg is recommended; the maximum possible dose for administration is 5000 IU.

    Advantages of 4-factor prothrombin complex concentrate over FFP include rapid reconstitution into a small volume for infusion over 20–30 minutes, fast onset of action, no requirement to check a patient’s blood group, minimal risk of viral transmission due to pathogen reduction and inactivation steps during manufacturing, and reduced risk of other clinical adverse reactions such as transfusion-associated circulatory overload or transfusion-associated acute lung injury. The latter is due to circulating antihuman leukocyte antigen or antigranulocyte antibodies in plasma. However, the 4-factor prothrombin complex concentrate does contain small amounts of heparin, and its use to reverse warfarin anticoagulation should be carefully considered in patients with heparin-induced thrombocytopenia.

    FFP contains all coagulation factors present in whole blood but it is not a factor concentrate, and multiple units may be needed if FFP alone is used for warfarin reversal. In addition to the inherent risks of plasma use mentioned already, requirements for its use include the need to determine the patient’s blood group (or to use group AB plasma), appropriate facilities for frozen plasma storage and thawing, and the time taken for infusion. Therefore, FFP should not be used routinely to reverse warfarin anticoagulation; however, where 4-factor prothrombin complex concentrate is unavailable and an emergency reversal is required, FFP should be used, along with vitamin K1 to sustain the reversal effect. Treating a patient with bleeding, regardless of INR For patients on warfarin therapy with bleeding in whom the aim is to normalize the INR, vitamin K1 given intravenously is the preferred treatment because of its faster and predictable onset of action. For this indication, doses 3 mg are ineffective. Consistent with other guidelines, we recommend a dose of 5–10 mg. For life-threatening (critical organ) and clinically significant bleeds, the consensus is to use the maximum dose of 4-factor prothrombin complex concentrate (with vitamin K1 and FFP) and the maximum amount of FFP when 4-factor prothrombin complex concentrate is unavailable.

    Among patients with an elevated INR up to 10.0 who do not have bleeding or risk factors for major bleeding, it has been shown that oral administration of low-dose vitamin K1 does not lower the risk of bleeding compared with placebo and should not be used routinely.36 However, for patients with risk factors for bleeding, vitamin K1 1–2 mg orally or 0.5–1.0 mg intravenously should be considered. Risk factors for major bleeding include a major bleed within the previous 4 weeks, surgery within the previous 2 weeks, a platelet count less than 50×109/L, known liver disease, or concurrent antiplatelet therapy. There are no randomized studies to guide the management of patients whose INR exceeds 10.0 and who are not bleeding. A recent single-arm study involving outpatients with an INR greater than 10.0 reported a low rate of major bleeding when these patients received 2.5 mg of oral vitamin K1. Many patients on warfarin are outpatients and information on individual patient bleeding risk is frequently not available to laboratory staff who are involved in reporting elevated INR results and attempting to communicate results to patients. In these settings, good communication between clinical and laboratory staff is essential.


    The recommended dose of 4-factor prothrombin complex concentrate to reverse the anticoagulant effect of warfarin according to the initial and target international normalized ratio (INR / INR) *

      Initial INR  
    Target INR1.5–2.52.6–3.53.6–10.0> 10.0
    0.9–1.330 IU/kg35 IU/kg50 IU/kg50 IU/kg
    1.4–2.015 IU/k25 IU/kg30 IU/kg40 IU/kg

    *Intern Med J 2011; 41: 337-343

    Fresh-frozen plasma is prescribed in the absence of a 4-factor concentrate of prothrombin complex.

    Fresh frozen plasma contains all the components of the coagulation system and the necessary proteins, but before administration, it is necessary to determine the patient’s blood group according to the ABO system, so the beginning of plasma infusion is often delayed. 10-15 ml/kg of plasma are entered. The following side effects may occur volume overload, allergic reactions, and others.

    Characteristics of 4-factor concentrate of prothrombin complex and fresh-frozen plasma

     Four-Factor Prothrombin Complex Concentrate (4F-PCC)Fresh frozen plasma
    DescriptionPrepared from plasma collected from voluntary donors. Sterile freeze-dried powder containing coagulation factors II, IX, and X and low levels of factor VIISeparated and frozen within 18 hours of collection from volunteer donors. Contains all coagulation factors
    ContraindicationsPatients showing signs of thrombosis or disseminated intravascular coagulationDo not use when coagulopathy can be corrected more effectively with specific therapy, such as vitamin K1, cryoprecipitate or other specific factor concentrates
    SpecificationsAvailable in vials containing 500 IU of factor II, IX, and X to be reconstituted in 20 mL of water for injections. Each vial also contains 25 IU of antithrombin and 192 IU of heparinAvailable in Australia in units of 250–334 mL and in New Zealand as 180–300 mL (typically 240–275 mL). It May be stored in a monitored blood refrigerator at 2–6°C for up to 5 days once thawed, and relabelled “thawed plasma” in accordance with Australian and New Zealand Society of Blood Transfusion Guidelines. Thawed plasma has levels of factors II, VII, IX, and X adequate for warfarin reversal
    AvailabilityFrom relevant blood service or hospital blood bankFrom relevant blood service or hospital blood bank
    Considerations for useNo need to consider the ABO blood groupAvailable in all ABO blood groups and should be ABO-group compatible with patient’s red cells (or use AB plasma)
     Known allergies to prothrombin complex concentrateThe most common adverse events — are allergic reactions and volume overload. Potential for transfusion-related acute lung injury and other transfusion reactions, including the transmission of infections
     Predisposition to venous thrombosis disseminated intravascular coagulation, and myocardial infarction 
     Heparin-induced thrombocytopenia 

    Management of patients on warfarin therapy with bleeding*

    Clinical settingRecommendations and levels of evidence†
    INR ≥1.5 with lifethreatening‡ (critical organ) bleedingCease warfarin therapy and administer:
    • vitamin K1 5.0–10.0 mg IV (2C)
    • and Prothrombinex-VF 50.0 IU/kg§ IV
    • and fresh frozen plasma 150–300 mL
    • If Four-Factor Prothrombin Complex Concentrate (4F-PCC) is unavailable, administer fresh frozen plasma 15 mL/kg
    INR ≥2.0 with clinically significant bleeding (not life-threatening)Cease warfarin therapy and administer:
    • vitamin K1 5.0–10.0 mg IV (2C)
    • and Prothrombinex-VF 35.0–50.0 IU/kg IV according to INR
    • If Four-Factor Prothrombin Complex Concentrate (4F-PCC) is unavailable, administer fresh frozen plasma 15 mL/kg
    Any INR with minor bleedingOmit warfarin, repeat INR the following day and adjust warfarin dose to maintain INR in the target therapeutic range (2C)
    • If the bleeding risk is high** or INR > 4.5, consider vitamin K1, 1.0–2.0 mg orally or 0.5–1.0 mg IV
      

    INR = international normalised ratio. IV = intravenously. * Indication for warfarin therapy should be reviewed; if clinically appropriate, consider permanent cessation. † Level of evidence in parentheses in bold. ‡ Includes intracranial bleeding. § Consider administering a Four-Factor Prothrombin Complex Concentrate (4F-PCC) dose less than 50.0 IU/kg when INR 1.5–1.9. ** Recent major bleed (within previous 4 weeks) or major surgery (within previous 2 weeks), thrombocytopenia (platelet count, < 50×109/L), known liver disease, or concurrent antiplatelet therapy

    Management of patients on warfarin therapy with high INR and no bleeding

    Clinical settingRecommendations and levels of evidence*
    INR<4.5 and no bleedingLower or omit the next dose of warfarin
    Resume therapy at a lower warfarin dose when the INR approaches the therapeutic range
    INR 4.5–10.0 and no bleeding• If the INR is only minimally above therapeutic range (up to 10%) dose reduction is generally not necessary (2C)
    • Cease warfarin therapy; consider reasons for elevated INR and patient-specific factors. Vitamin K1 is usually unnecessary (2C)
    • If the bleeding risk is high:† consider vitamin K1 1.0–2.0 mg orally or 0.5–1.0 mg IV
    • measure INR within 24 h
    • resume warfarin at a reduced dose once INR approaches therapeutic range
    INR > 10.0 and no bleeding• Cease warfarin therapy, administer 3.0–5.0 mg vitamin K1 orally or IV‡ (2C)
    • Measure INR in 12–24 h. Close monitoring of INR daily to second daily over the following week
    • Resume warfarin therapy at a reduced dose once INR approaches therapeutic range
    • If the bleeding risk is high:† consider Four-Factor Prothrombin Complex Concentrate (4F-PCC), 15–30 IU/kg
    • measure INR in 12–24 h. Close monitoring over the following week
    • resume warfarin therapy at a reduced dose once INR approaches the therapeutic range

    INR = international normalised ratio. IV = intravenously. * Level of evidence in parentheses in bold; details. Recommendations with no evidence level are standard practice and not based on gradable evidence. † Recent major bleed (within previous 4 weeks) or major surgery (within previous 2 weeks), thrombocytopenia (platelet count, < 50х109/L), known liver disease, or concurrent antiplatelet therapy. ‡ Extrapolated from oral vitamin K data in absence of IV data.

    Bleeding whilst taking warfarin

    1. Explain that the main side effect of warfarin is bleeding more easily than normal
    2. Explain the common types of ‘less serious bleeding’ and what to do if they experience them
    3. Explain the rarer types of ‘serious bleeding’ and what to do if they experience them

    The main side effect of warfarin involves bleeding more easily than normal (e.g. epistaxis, bleeding gums, heavier periods, bruising). These side effects most commonly occur in the first few weeks of treatment or when the patient is unwell. It is important to discuss the different types of bleeding the patient may experience and inform them what to do in these situations.

    Less serious bleeding Minor bleedingSerious bleeding Major bleeding
    “It is normal to bleed more easily when taking warfarin as the medication works by thinning the blood.

    Common types of bleeding include
    – periods that are heavier and last longer than normal
    – bleeding for a little longer than usual if you cut yourself
    – occasional nosebleeds (that last for less than 10 minutes)
    – bleeding from your gums when you brush your teeth
    – bruised that come up more easily and take longer to fade than usual.

    This type of bleeding is not dangerous and should stop by itself. If it happens, keep taking the warfarin, but tell your doctor if the bleeding bothers you or does not stop.”    		“Occasionally, you can have serious bleeding from taking warfarin. This can be dangerous and needs urgent medical attention.”
    “Stop taking warfarin and call your doctor or anticoagulant clinic, or go to A&E if you experience:
    – red pee or black poo,
    – large bruises or bruises that happen for no reason,
    – nosebleeds that last longer than 10 minutes,
    – blood in your vomit or you’re coughing up blood,
    – severe headaches, fits (seizures), changes to your eyesight, numbness or tingling in your arms or legs, or feeling very tired, weak, or sick – these can be signs of bleeding in your brain
    – any bleeding from a cut or injury that will not stop or slow down”

    How to take warfarin

    1. Explain that warfarin should be taken at the same time each day
    2. Explain the different types of warfarin tablets
    3. Explain what the patient should do if they forget a dose
    4. Advise the patient to let medical professionals know that they take warfarin when they are being prescribed new medications
    5. Advise the patient to let the team managing their anticoagulation know when they start taking a new medication
    6. Advise the patient about the importance of effective contraception if taking warfarin (if relevant)

    Key points to communicate when discussing warfarin use:

    • “Warfarin should be taken at the same time each day to keep the levels of warfarin steady.”
    • “Tablets have different colours depending on their strength (e.g. 0.5mg white; 1mg brown; 3mg blue; 5mg pink).”
    • “If you forget to take a dose you should take it as soon as you remember, but if you don’t remember till the following day you should skip the missed dose. You should never take two doses together to make up for a missed dose and you should inform your doctor or warfarin clinic about any missed doses at your next appointment.”
    • “Whenever you are going to purchase or be prescribed a new medication you should let the doctor or pharmacist know that you take warfarin so they can avoid prescribing medications which alter your warfarin level.”
    • “When you start taking a new medication you should let your doctor or anticoagulant clinic know so that they can consider if your warfarin levels need monitoring more frequently.”
    • “You should continue to take your warfarin tablets regularly until you have been told to stop.”
    • “Warfarin is not safe to be used during pregnancy and therefore you should have an effective contraceptive method in place before you start taking warfarin.”
    • “You must inform anticoagulant healthcare staff if you think you have taken too much warfarin or have missed any doses.”
    • “You must inform the relevant healthcare professionals if you start, stop or change the dose of your medicines, or if your diet changes substantially (eg. intake of broccoli, lettuce or spinach /)”Other medicines” include not only prescribed drugs but also products that may be brought without prescription, such as aspirin,  and medicines containing aspirin, vitamins, food supplements and herbal or homoeopathic remedies.”
    • “If you require surgery, dental work, or any other invasive procedure you may need stop taking warfarin temporarily. You should discuss your warfarin management with a healthcare professional prior to the procedure”.

    Tips for further warfarin dosing according to the analysis of the reasons that led to the INR levels increase

    1. Estimate the required duration of administration of a concomitant drug that interacts with warfarin (temporary, chronic) as needed
    2. Adjust warfarin dosage as needed
    3. Withdraw warfarin if necessary
    4. Evaluate the rationality and necessity of co-administration of antiplatelet agents and nonsteroidal anti-inflammatory drugs if necessary
    • Most common drugs that can increase INR:
      • Antibiotics: sulfamethoxazole/trimethoprim, metronidazole, quinolones (ciprofloxacin, levofloxacin), amoxicillin, erythromycin, clarithromycin, azithromycin
      • Azole antifungals: fluconazole, miconazole, voriconazole
      • Cardiac drugs: amiodarone, some statins (fluvastatin), fenofibrate
      • Acetaminophen >1 g/day
      • Levothyroxine dose increases – full effect observed after 4‐6 weeks of dose change
    • Management strategy:
      • If the interacting drug is temporary and significantly increases the INR, may temporarily hold and/or reduce the maintenance dose of warfarin until the interacting effect resolves.
      • If the interacting drug will be used chronically, modify the warfarin dose according to a
      • dosing nomogram.
      • Although warfarin interacts with many drugs, virtually no drug requires complete avoidance in a patient who is also taking warfarin therapy (or vice versa). Increasing the frequency of INR tests, initially, allows for appropriate dosing adjustments, if necessary.
      • There may be some exceptions to this approach. For example, patients receiving chemotherapy with emesis or infection may have INR fluctuation that is difficult to control.
      • In such cases, switching the patient to a low molecular weight heparin (LMWH) until stabilization of the underlying condition is suggested.
      • Note: Antiplatelet agents (acetylsalicylic acid [ASA], clopidogrel, prasugrel, ticagrelor) and Non‐steroidal Anti‐Inflammatory Drugs (NSAIDs) significantly increase the risk of bleeding when combined with warfarin but generally do not change the INR. The indication and clinical necessity of using these agents should be carefully weighed against the increased bleeding risk.

    Strategy approach in a patient with altered health states

    • Transient infectious illness (fever and/or diarrhea):
      • Fever increases the metabolic state which may result in depletion of clotting factors and increased INR.
      • Being ill can also alter diet and may lead to a transient vitamin K deficiency.
    • Uncontrolled hyperthyroidism – leads to increased clearance of clotting factors, resulting in high INR.
    • Congestive heart failure (CHF) exacerbation (perhaps due to liver congestion).
    • Management Strategy:
      • Temporarily reduce the warfarin dose and increase the frequency of INR monitoring until the patient’s health state stabilizes

    Algorithm for warfarin dose adjusting

    It may be necessary to (temporarily) reduce the dose of warfarin and/or skip one or two doses based on the assessment of INR level. The INR should be re-measured to be sure about its decreasing after two or three days.

    INRRecommended dose adjustment of warfarin
    <1.5Increase the weekly dose by 10-20%
    Consider additional doses
    INR control in 4-8 days under the doctor consideration
    1.5 to <2Increase the weekly dose by 10-20%
    INR control in 4-8 days under the doctor consideration
    2.0-3.0Unchanged
    >3.0 to 3.5Decrease the weekly dose by 10-20%
    INR control under the doctor consideration
    4.0 to >5.0Skip 0 to 1 dose
    and/or reduce the weekly dose by 0-20%
    INR control under the doctor consideration
    >4.0 but >5.0Skip 1-2 doses and reduce the weekly dose by 10-20%
    INR control in 3-7 days under the doctor consideration
    5.0 to >9.0
    without significant bleeding    		Skip 1-2 doses
    INR control in 1-2 days under the doctor consideration
    To resume warfarin taking when INR <3.0 with a decrease in a weekly dose by 5-20%
    If urgent surgery is required, the patient should be given fresh-frozen plasma
    ≥9.0
    without significant bleeding    		Do not take warfarin
    Assign vitamin K (2.5-5 mg orally once)
    INR control daily to > 3.0, reducing the weekly dose by 10-20%
    If urgent surgery is required, the patient should be given fresh-frozen plasma

    Altered Nutritional Status

    • Patients who are malnourished are commonly vitamin K deficient.
    • Sudden changes in diet may be due to social circumstances such as a death of a spouse/family member/pet or stressful work or health situations.
    • Management Strategy:
      • Ask the patient to describe their eating pattern and intake.
      • Recommend eating consistent meals or use of a meal replacement beverage (e.g. 4 cans of
      • Ensure contain the required daily amounts of nutrients) or multivitamins containing vitamin K.
      • If this is not successful, consider lowering the maintenance dose and increasing the frequency of monitoring.

    Alcohol consumption

    Even a single moderate consumption or a large amount of alcohol consumed (more than two glasses) can temporarily increase the INR level (for example, alcohol consumption on weekends). In case of cessation of alcohol intake, it is possible to continue the usual maintenance dose.

    It is recommended alcohol abuse prevention.

    Errors in dosing

    The patient may have mistakenly taken a different dosage regimen than what was prescribed.

    Management Strategy:

    • Ask the patient exactly what doses they have taken in the past 2 weeks and review their dosing calendar.
    • Ask the patient to bring in all of their medications and pill box to ensure the correct drugs and doses are being taken. If the patient has a good relationship with their local pharmacy, ask the pharmacist to double check.
    • Use a warfarin dosing calendar. Encourage the patient to use a calendar to record their INRs and warfarin doses taken.
    • Use a warfarin dosette (pill box). The patient or caregiver puts the daily doses in a weekly pill box.
    • Simplify the dosing regimen. Use of a single tablet strength to avoid multiple strength confusion and strategically putting extra/reduced daily doses on days that are easy to remember (e.g. “Take 1 tablet every day except take 2 tables on Sundays.”

    Lifestyle advice

    1. Advise the patient about the impact of diet on the effect of warfarin
    2. Advise the patient about the impact of alcohol on the effect of warfarin
    3. Advise the patient about brushing teeth, shaving and dental procedures
    DietDrastic changes in diet, especially an increase in consumption of foods high in vitamin K (such as broccoli, kale, or spinach) can potentially affect the control of anticoagulation.

    If the patient ever wishes to significantly change their diet, they should inform the anticoagulant clinic so necessary dose adjustments and monitoring requirements can be fulfilled. “Since vitamin K and warfarin work against each other, the amount of vitamin K in your diet can change warfarin’s effects. It is important to keep your dietary intake of vitamin K consistent. Foods such as green leafy vegetables and certain oils have higher contents of vitamin K. (See the table below for a chart of vitamin K content in selected foods).

    If you DECREASE your intake of vitamin K (eat fewer foods containing vitamin K) your dose of warfarin may need to be lowered to prevent bleeding. If you INCREASE your intake of vitamin K, your dose of warfarin may need to be increased to prevent blood clots. A MAJOR change in your vitamin K intake can affect your PT/INR, but normal daily variation in the foods you eat is okay.

    You DON’T have to avoid foods that are high in vitamin K, just keep your diet consistent. You should let your healthcare professional know if there is going to be a major change in your diet, so your PT/INR can be closely monitored”

    Many people are on special diets, such as the Atkin’s or South Beach diets, to lose weight. These diets are high-protein diets and can also affect the way warfarin works in your body. Once you take a dose of warfarin, some of it binds to protein in your bloodstream. While warfarin is attached to this protein, it has no effect on your body. It’s thought that high protein diets can increase the number of proteins in your body and cause more warfarin to be bound to protein.

    This causes a DECREASE in warfarin available to prevent clots, so your warfarin dose may need to be increased. Always check with your healthcare professional before starting any special diets, so your PT/INR can be closely monitored.  

    Certain foods can also affect how your liver clears warfarin from your body, causing warfarin levels to increase or decrease. Examples include alcohol, cranberry products (e.g., juice, supplements), and possibly grapefruit or grapefruit juice. Too much alcohol, cranberry products, or grapefruit products can INCREASE warfarin’s effect and increase your risk of bleeding. Avoid or limit your intake of alcohol, cranberry products, and grapefruit or grapefruit juice.

    Make sure your healthcare professional knows if your diet contains any of these products, so your PT/INR can be closely monitored. Cranberry juice is also known to interact with warfarin and enhance its anticoagulant effect and therefore it should be avoided.    

    “People on vitamin K-rich diets should not change eating habits without at the same time reducing the warfarin dosage, because excessive anticoagulation and bleeding may occur.”  
    Alcohol  Patients should limit their alcohol intake to a maximum of one or two drinks a day and never binge drink.
    If there are major changes in alcohol consumption (e.g. the patient stops drinking, or starts drinking more) the INR can be affected.  
    “People should limit the amount of alcohol to a maximum of one or two drinks a day and never bridge drink.”
    OtherPatients should be advised to take extra care when carrying out routine tasks such as brushing teeth or shaving; a soft toothbrush or an electric razor can help. Patients should also be advised to inform their dentist that they take warfarin when booking an appointment as this may have implications for dental procedures.  

    “Other things to remember when taking warfarin In addition to foods, many prescription and over-the-counter drugs, including vitamins and herbal supplements, can affect your warfarin level. You should not start, stop, or change doses of any drugs or supplements without first talking with your healthcare professional. Try to keep a healthy, well-balanced diet and keep your vitamin K intake consistent. Take your warfarin dose around the same time each day. If you miss a dose, take it as soon as you remember. If it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Don’t double up doses without checking with your healthcare professional. Tell your healthcare professional immediately if you have unusual bleeding or bruising, black or bloody stools, blood in the urine, or stomach pain.”

    “People should avoid activities which could cause abrasion, bruising or cuts (eg., contact sports, gardening, sewing), or at least use protection.”

    People should avoid insect bites, especially on their legs, and should use a repellent when exposed to insects.   Patients with deep vein thrombosis should be given the following additional lifestyle advice: regular walking exercise helps to reduce the risk of further deep vein thrombosis and improves circulation in the affected limb the affected leg should be elevated when sitting “If you are traveling for any length of time will need to move your dosing time gradually  – say by an hour a day – to a time that is convenient to the new zone. You may also need to have an INR check while you are away.”

    Yellow booklets and alert card

    1. Remind the patient with information about the INR monitoring booklet and patient information booklet
    2. Remind the patient the importance of carrying the anticoagulant alert card with them at all

    At the start of treatment, all patients should be provided with two yellow anticoagulant booklets, an INR monitoring booklet, and a patient information booklet. Patients should also be provided with an anticoagulant alert card.

    Patients should be advised to always carry the anticoagulant alert card with them in case of an emergency and always take the yellow INR monitoring book with them to each appointment at the anticoagulant clinic and if possible to other appointments (e.g. GP, pharmacy reviews, dental appointments, etc).

    The patient information book is a useful resource since it provides the patient with a point of reference and reinforces what has been covered in this guide.

    Closing the consultation

    1. Summarise the key points back to the patient
    2. Ask the patient if they have any questions or concerns that have not been addressed
    3. Arrange appropriate follow-up
    4. Thank the patient for their time
    5. Dispose of PPE appropriately and wash your hands

    Key communication skills

    Summarise the key points back to the patient.

    Ask the patient if they have any questions or concerns that have not been addressed.

    If you feel that the patient would benefit from a recap session, arrange a follow-up appointment (face-to-face or telephone) and also direct the patient to the yellow anticoagulant information booklet for further reading.

    Thank the patient for their time.

    Dispose of PPE appropriately and wash your hands.

    Key communication skills

    1. Active listening
    2. Summarising
    3. Signposting

    Key clinical skills

    1. Determining the target INR level depending on the clinical situation
    2. Analysis of the factors that may affect the INR increase
    3. Providing medical care to the patient with INR increase
    4. Advice to the patient and explanations about lifestyle, diet

    If necessary, re-detail Counseling a patient who is taking warfarin / OSCE guide

    Join our simulation training to gain clinical experience

    Clinical case simulator “Mysteries of the heart”
    Clinical case simulator “An interrupted symphony”

    Supplements materials

    Principles for preventing high international normalised ratio (INR)

    • When starting warfarin therapy, avoid high loading doses of warfarin. In general, it is preferable to start treatment using an initial daily dose of 5 mg, or even lower in elderly patients. However, some guidelines have suggested that patients who are considered sufficiently healthy may receive warfarin 10 mg daily for the first 2 days with subsequent doses to be determined by the INR (2C)
    • Consider potential warfarin–drug interactions. Avoid concomitant non-steroidal antiinflammatory drugs and certain antibiotics (2C). Avoid concomitant antiplatelet therapy except where clinical benefit is known, such as mechanical heart valves, acute coronary syndrome, or recent insertion of coronary stents (2C)
    • Test the INR more frequently after starting, stopping or changing the dose of concomitant medication
    • Avoid frequent dose adjustments. A change in warfarin dose will take several days to influence the INR, so testing the INR within 24 or 48 hours of a dose change may not truly reflect the steady-state response to the dose adjustment
    • Avoid excessive increases in dose when the INR drifts below the target INR range
    • Effective patient education can minimise compliance problems
    • Pharmacogenetic testing to guide warfarin dosing is not necessary (1B)

    Vitamin K Content of Selected Foods

    * Note: This is NOT a list of foods to avoid. This list provides information on the vitamin K content of certain foods.

    FoodsLowModerateHigh
    VegetablesGreen beans    AsparagusBroccoli
     CarrotsAvocadoBrussels sprouts
     CauliflowerRed CabbageCabbage
     CeleryGreen peasCollard greens
     Corn Endive (raw)
     Cucumber (peel removed)Pickle (dill)Kale (raw leaf)
     EggplantLettuce (iceberg)Lettuce (bib, red leaf)
     Mushrooms Mustard greens (raw)
     Onions Parsley
     Green pepper Spinach
     Potato Turnip greens (raw)
     Pumpkin Watercress (raw)
     Sauerkraut (canned) Swiss chard
     Tomato  
    FruitsApple  
     Banana  
     Blueberries  
     Grapes  
     Orange  
    MeatsBeef  
     Chicken  
     Pork  
     Tuna  
       Turkey  
    Fats and OilsCorn oilMargarineMayonnaise
     Peanut oilOlive oilCanola oil
     Safflower oil Soybean oil
     Sesame oil  
     Sunflower oil  
    Dairy ProductsButter  
     Cheese (cheddar)  
     Eggs  
     Sour cream  
     Yogurt  
    BeveragesCoffee  
     Cola  
     Fruit juices  
     Milk  
     Tea (black) Tea (green)**
    * Adapted with permission from Clotcare Online Resource at www.clotcare.com. (Accessed April 20, 2005)
    ** There is some controversy as to whether brewing green tea alters the vitamin K content and/or whether green tea may alter the effect of warfarin by some other mechanism

    Potential Interactions of Dietary Supplements with Warfarina

    Potential Increase in Risk of Bleeding  
    Acetyl-L-carnitineFish oilMate
    ArnicaFlaxseed, Flaxseed oilMelatonin
    Alcohol, acute useFo-tiMesoglycan
    Bishop’s weedForskolinMilk thistle
    Black teaForsythiaN-acetyl glucosamine
    BladderwrackGamma-linolenic acidNattokinase
    BoldoGarlicOolong tea
    Borage seed oilGingerPantethine
    BurdockGinkgoPapaya
    CaffeineGinseng, SiberianPeppermint oil
    Chondroitin sulfateGlucosaminePropionyl-L-carnitine
    Cod liver oilGrapefruit, Grapefruit juiceRed clover
    ColtsfootGuaranaReishi mushroom
    Cranberry, cranberry juiceGuggulResveratrol
    DanshenHoly basilSaw palmetto
    Devil’s clawHoneysuckleSea buckthorn
    Dong quaiHorse chestnutTiratricol
    EpimediumIpriflavoneTurmeric
    Eucalyptus oilJiaogulanVinpocetine
    Evening primrose oilKavaVitamin A
    FenugreekL-carnitineVitamin E
    FeverfewLyciumWillow bark
      Wintergreen
    Possible Decrease in Warfarin’s Effects  
    Acerola  
    Alcohol, chronic use  
    Alfalfa  
    Cherokee rosehip  
    Chlorella  
    Coenzyme Q10  
    Corn silk  
    EDTA  
    Ginseng, American  
    Ginseng, Panax  
    Green tea  
    Limonene  
    Rose hip  
    Smartweed  
    Soy  
    Spinach  
    St. John’s wort  
    Stinging nettle  
    Vitamin C  
    Vitamin K  
    Watercress  
    aAdapted from Natural Medicines Comprehensive Database at www.naturaldatabase.com. (Accessed 4/21/05)

    Vitamin K and other Potential Interactions with warfarinDownload

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    • Opening the consultation

    • Ideas, concerns, complications and expectations

    • Analysis of earlier, current INR results, apropriate INR target range and current warfarin dosing

    • Analysis of the factors that may affect the increased INR level

    • Providing medical care to the patient if necessary

    • Bleeding whilst taking warfarin

    • How to take warfarin

    • Tips for further warfarin dosing according to the analysis of the reasons that led to the INR levels increase

    • Lifestyle advice

    • Yellow booklets and alert card

    • Closing the consultation

    • Key communication skills

    • Key clinical skills

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    Clinical case simulator – Sudden INR increase in the women with prosthetic mitral valve taking warfarin
    Counseling a patient who is taking warfarin / OSCE guide

    Literature:

    1. 12020 ACC Expert Consensus Decision Pathway on Management of Bleeding in patients on oral anticoagulants: a report of the American College of cardiology solution set oversight committee. Jam Coll Cardiol. 2020. Aug, Vol.76 (5). 594-622.
    2. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACT). Supplementary data. European Heart Journal (2020), 42, 373-498.
    3. Huyen A Tran et al. Guidelines. An update of consensus guidelines for warfarin reversal. MJA. 2013; Vol.198(4): 7 P. doi: 10.5694/mja12.10614
    4. What You Should Know About Your Diet and Warfarin. PHARMACIST’S LETTER / Prescriber’s Letter to give to their patients. P.O. Box 8190, Stockton, CA 95208. May 2005 ~ Volume 21 ~ Number 210507, 8 p.
    5. Beatty SJ, Mehta BH, Rodis JL. Decreased warfarin effect after initiation of high-protein, lowcarbohydrate diets. Ann Pharmacother 2005;39:744
    6. Committee on Safety of Medicines (CSM). Current Problems in Pharmacovigilance 2003;29:8.
    7. Shields KM. Possible Cranberry and Warfarin Interaction. Pharmacist’s Letter/Prescriber’s Letter 2003;19(11):191103.
    8. Havrda DE, Mai T, Chonlahan J. Enhanced antithrombotic effect of warfarin associated with low-dose alcohol consumption. Pharmacotherapy 2005;25:303-7.
    9. OXFORD HAEMOPHILIA AND THROMBOSIS CENTRE PROTOCOLS FOR OUTPATIENT ORAL ANTICOAGULATION WITH VITAMIN K ANTAGONISTS. Prepared by D. Keeling with input and review from S. Shapiro, N. Curry, V. Price, and L. Mulholland.AC Protocols version 4.1 May 2017
    10. Paulus Kirchhof, Stefano Benussi, Dipak Kotecha, Anders Ahlsson, Dan Atar, Barbara Casadei, Manuel Castella, Hans-Christoph Diener, Hein Heidbuchel, Jeroen Hendriks, Gerhard Hindricks, Antonis S. Manolis, Jonas Oldgren, Bogdan Alexandru Popescu, Ulrich Schotten, Bart Van Putte, Panagiotis Vardas, Stefan Agewall, John Camm, Gonzalo Baron Esquivias, Werner Budts, Scipione Carerj, Filip Casselman, Antonio Coca, Raffaele De Caterina, Spiridon Deftereos, Dobromir Dobrev, José M. Ferro, Gerasimos Filippatos, Donna Fitzsimons, Bulent Gorenek, Maxine Guenoun, Stefan H. Hohnloser, Philippe Kolh, Gregory Y. H. Lip, Athanasios Manolis, John McMurray, Piotr Ponikowski, Raphael Rosenhek, Frank Ruschitzka, Irina Savelieva, Sanjay Sharma, Piotr Suwalski, Juan Luis Tamargo, Clare J. Taylor, Isabelle C. Van Gelder, Adriaan A. Voors, Stephan Windecker, Jose Luis Zamorano, Katja Zeppenfeld, 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS, EP Europace, Volume 18, Issue 11, November 2016, Pages 1609–1678, https://doi.org/10.1093/europace/euw295

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    Lyme disease is an infectious disease caused by the spirochete Borrelia burgdorferi, which is transmissible…

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    Сообщение Patient’s counseling with an increased INR level / OSCE guide появились сначала на ClinCaseQuest.

    ]]>         Interactive Checklist of differential diagnoses of DILI and HILI https://clincasequest.hospital/checklist-differential-diagnoses-dili-hili/ Thu, 03 Feb 2022 07:55:00 +0000 https://clincasequest.hospital/?p=33174 Differential diagnoses of drug-induced and herb-induced liver disease: Checklist of differential diagnoses of DILI and HILI. This tabular listing, although not comprehensive, is to be…

    Сообщение Interactive Checklist of differential diagnoses of DILI and HILI появились сначала на ClinCaseQuest.

    ]]>     Differential diagnoses of drug-induced and herb-induced liver disease: Checklist of differential diagnoses of DILI and HILI.

    This tabular listing, although not comprehensive, is to be used as a guide and in connection with the updated RUCAM, derived from a previous publication.

    Loading...

    Abbreviations: AAA, Anti-actin antibodies; AMA, Antimitochondrial antibodies; ANA, Antinuclear antibodies; ASGPR, Asialo-glycoprotein-receptor; BMI, Body mass index; CT, Computed tomography; CYP, Cytochrome P450; PDH, Pyruvate dehydrogenase; HAV, Hepatitis A virus; HBc, Hepatitis B core; HBV, Hepatitis B virus; HCV, Hepatitis C virus; HEV, Hepatitis E virus; HILI, Herb induced liver injury; HIV; human immunodeficiency virus; LKM, Liver kidney microsomes; LP, Liver-pancreas antigen; LSP, Liver specific protein; MRC, Magnetic resonance cholangiography; MRT, Magnetic resonance tomography; p-ANCA, Perinuclear antineutrophil cytoplasmic antibodies; PCR, Polymerase chain reaction; RUCAM, Roussel Uclaf Causality Assessment Method; SLA, Soluble liver antigen; SMA, Smooth muscle antibodies; TSH, Thyroid stimulating hormone; TTG, Tissue transglutaminase

    Differential Diagnosis / Diagnostic Parameters

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    See also:

    RUCAM scale to estimate the probability of the drug-induced liver injury (DILI) and herb induced liver injury (HILI) online calculator
    Child-Pugh Score for Cirrhosis Mortality: online calculator
    King’s College Criteria for Non- Acetaminophen Toxicity acute hepatic failure
    King’s College Criteria for Acetaminophen Toxicity

    Сообщение Interactive Checklist of differential diagnoses of DILI and HILI появились сначала на ClinCaseQuest.

    ]]>         RUCAM scale to estimate the probability of the drug-induced liver injury (DILI) and herb induced liver injury (HILI) online calculator https://clincasequest.hospital/rucam-scale/ Tue, 01 Feb 2022 07:15:00 +0000 https://clincasequest.hospital/?p=32949 The RUCAM score (Roussel Uclaf Causality Assessment Method) helps to assess the likelihood of drug-induced liver injury (DILI), as well as the assessment of the…

    Сообщение RUCAM scale to estimate the probability of the drug-induced liver injury (DILI) and herb induced liver injury (HILI) online calculator появились сначала на ClinCaseQuest.

    ]]>     The RUCAM score (Roussel Uclaf Causality Assessment Method) helps to assess the likelihood of drug-induced liver injury (DILI), as well as the assessment of the likelihood of herb-induced liver injury (HILI). Previous name CIOMS (Council for International Organizations of Medical Sciences).

    Causality assessment by the updated RUCAM requires prior evaluation of liver injury criteria and its pattern in each suspected case 

    Respective criteria are readily assessable by initial measurement of ALT (alanine aminotransferase) and ALP (alkaline phosphatase).

    Updated RUCAM for the Hepatocellular Liver Injury of DILI and HILI.

    Drug-induced liver injury is a diagnosis of exclusion, even in cases where the liver injury is likely to be drug-related, the doctor needs to perform a detailed analysis according to certain parameters given in the rating scale.

    To assess the causality of drug-induced liver injury (DILI) on the RUCAM scale, it is necessary to select the variant of liver injury (hepatocellular or cholestatic/mixed) and evaluate the indicators corresponding to the variant of liver damage, after the assessment, it is necessary to sum the scale indicators and interpret the scores.

    Evaluation of causality using the updated RUCAM requires a preliminary assessment of the criteria for liver injury and its nature in each suspected case.

    Appropriate criteria are easily assessed by initially measuring ALT (alanine aminotransferase) and ALP (alkaline phosphatase).

    Liver injury is defined by increased serum activities of ALT of at least 5N and/or of ALP of at least 2N, best assessed simultaneously on the day of first presentation (N – upper limit of normal). These thresholds will increase the specificity of the hepatotoxicity causality assessment, eliminates false positive cases, and substantiates hepatotoxicity causality at a high level of probability. They are also in line with a recent consensus on DILI. However, when ALT is within the normal range, ALP increases should be paralleled by increased γ-glutamyltranspeptidase or better 5’ nucleosidase to rule out isolated increases of ALP activities due to bone or another origin rather than hepatobiliary disease

    In accordance with the original RUCAM, the updated RUCAM takes into account divergent laboratory constellation of the liver injury and provides two different subscales: one for the hepatocellular type of injury and the other one for the cholestatic or mixed type of injury. These types can be differentiated using the ratio R, calculated as the ALT/ ALP activity measured at the time liver injury is suspected, with both activities expressed as multiples of N.

    • The liver injury is hepatocellular if ALT > 5N and ALP ≤ N, or if both ALT and ALP are elevated, R ≥ 5;
    • the liver injury is cholestatic if ALP > 2N and ALT ≤ N, or if both ALT and ALP are elevated, R ≤ 2;
    • the liver injury is mixed if ALT > 5N and ALP > N and 2 < R < 5.

    This classification of liver injury pattern clearly assigns each DILI or HILI case to the updated RUCAM, either for the hepatocellular injury (Table Hepatocellular Liver Injury) or the cholestatic and mixed liver injury (Table Cholestatic or Mixed Liver injury).

    Pregnancy is a risk factor only for the cholestatic and mixed liver injury, not for the hepatocellular injury (Table Cholestatic or Mixed Liver injury).

    Loading...

    According to your lab

    According to your lab

    * Required


    RUCAM scale online calculator

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    Select the type of liver injury: hepatocellular or cholestatic/mixed:

    1. Time to onset from the beginning of the drug/herb

    2. Course of ALT after cessation of the drug/herb

    (percentage difference between ALT peak and N)

    2. Course of ALP after cessation of the drug/herb

    (percentage difference between ALP peak and N)

    3. Risk factors

    4. Concomitant use of drug(s)/herb(s)

    5. Search for alternative causes

    Check out the causes that can be ruled out!

    Check out the causes that can be ruled out!

    6. Previous hepatotoxicity of the drug/herb

    7. Response to unintentional reexposure

    Abbreviations: ALT, Alanine aminotransferase; AST, Aspartate aminotransferase; CMV, Cytomegalovirus; CT, Computer tomography; DILI, Drug induced liver injury; EBV, Epstein Barr virus; HAV, Hepatitis A virus; HBc, Hepatitis B core; HBsAg, Hepatitis B antigen; HBV, Hepatitis B virus; HCV, Hepatitis C virus; HEV, Hepatitis E virus; HILI, Herb induced liver injury; HSV, Herpes simplex virus; MRC, Magnetic resonance cholangiography; N, upper limit of the normal range; RUCAM, Roussel Uclaf Causality Assessment Method; VZV, Varicella zoster virus. Total score and resulting causality grading: ≤0, excluded; 1–2, unlikely; 3–5, possible; 6–8, probable; and ≥9, highly probable


    Evaluation of the relationship between liver injyry and taking the drug by the number of points:

    Each element of the updated RUCAM is assigned an individual score, and the sum of the individual scores gives the final score for the case. From +14 to -9 points, there is a wide range of final grades.Total score and resulting causality grading:

    • ≤0 points – excluded
    • 1-2 points – unlikely
    • 3-5 points – possible
    • 6-8 points – probable
    • >9  points  – highly probable

    What should be considered when using this rating scale?

    Operational Information on the Updated RUCAM

    1. RUCAM affords prospective use, since retrospective scoring is less accurate.
    2. RUCAM is to be calculated individually for each co-administered product.        
    3. RUCAM is conceptualized primarily for idiosyncratic, not for intrinsic reactions.
    4. RUCAM excludes cases with onset of hepatic injury before start of product use.
    5. RUCAM is applicable only for acute liver injury, not for preexisting chronic liver disease.        
    6. RUCAM cannot correctly assess when ALP is elevated for non-hepatic reasons. 
    7. Concomitant use of drugs and herbs is a crucial item that is best inquired and documented at first presentation when liver injury is suspected. Details of a temporal association and potential hepatotoxic features of the used product are to be assessed and documented. For reasons of comparison and transparency, each comedicated drug or herb requires a separate analysis by the complete updated RUCAM. In patients with use of multiple drugs or herbs, the final causality should be attributed primarily to the product with the highest score achieved with the updated RUCAM.

    Previous Hepatotoxicity

    Hepatotoxicity listed in the product information sheet (e.g., Summary of product characteristics in the EU or product information in the US) must be checked, although the terms used to express the liver injury may vary and usually do not refer to specific definitions. If it is mentioned, then the hepatotoxicity is considered as known for that compound. If this toxicity is not mentioned, a quick literature search in PubMed and the well documented NIH LiverTox website are recommended to determine whether the product has already been involved in published DILI and HILI.

    Response to Unintentional Reexposure

    A positive reexposure test result is a hallmark and gold standard in DILI cases and recognized by respective scores. To classify a reexposure test as positive, few criteria are required, as specified. The respective criteria were based on the conclusions of International Consensus Meetings in 1988 and 1990, as reviewed previously and recently. For the hepatocellular type of injury, the defining criteria are ALT levels before reexposure (designated as baseline ALT or ALTb), and reexposure ALT levels (designated as ALTr). The reexposure test is positive if ALTb is <5N and ALTr is ≥2ALTb, negative if one or both criteria are not fulfilled, and uninterpretable if data are lacking for one or both criteria. For the cholestatic or the mixed liver injury, the assessment criteria and interpretation of results are similar, with ALT replaced by ALP (Table).

    Conditions of unintentional reexposure tests in suspected DILI and HILI cases.

    Reexposure Test ResultHepatocellular Injury Cholestatic or Mixed Liver Injury 
     ALTbALTrALPbALPr
    ●   Positive<5N≥2ALTb<2N≥2ALPb
    ●   Negative<5N<2ALTb<2N<2ALPb
    ●   Negative≥5N≥2ALTb≥2N≥2ALPb
    ●   Negative≥5N<2ALTb≥2N<2ALPb
    ●   Uninterpretable<5Nn.a.<2Nn.a.
    ●   Uninterpretablen.a.≥2ALTbn.a.≥2ALPb
    ●   Uninterpretablen.a.n.a.n.a.n.a.

    The original RUCAM was tested for its validity with the use of DILI cases confirmed by positive rechallenge taken as the gold standard and DILI cases where there was strong evidence that drugs were not the culprit drugs. As the updated RUCAM does not change fundamentally the structure and the weights of the original method there is no reason to consider a change in its validity. Presently, all relevant clinical diagnostic parameters are included in the updated RUCAM and in the checklist. There is little evidence that liver histology adds substantially to the diagnosis of DILI or HILI, as these lack specific histopathological features since they mimic all primary hepatic and biliary diseases. Therefore, liver histology is not part of the diagnostic program of the updated RUCAM. However, it is possible to take into account the results of a liver biopsy examination to exclude an alternative cause but certainly not to confirm DILI or HILI.

    Search for Alternative Causes

    In this domain, the updated RUCAM scale considers the clinically most relevant alternative causes and complications of underlying disease(s). Antibodies are important tools but require assessment and approval by regulatory agencies. Problems of diagnosing infections by hepatitis E virus (HEV) are evident in the US with anti-HEV antibody tests that are not FDA approved. Most importantly, titer changes of antibodies in suspected hepatic viral infections are to be evaluated in the further clinical course to confirm or disprove an ongoing virus infection.

    Rare alternative causes are included in a checklist of differential diagnoses as a reminder for the clinician that many diagnoses exist as alternatives to DILI and HILI. These other diagnoses are to be considered, excluded or verified in the context of clinical data and importance, financial resources, and benefit for the patient. Establishing alternative causes contributes to the accuracy of the updated RUCAM and often provides clues to possible specific therapies.

    Checklist of differential diagnoses of DILI and HILI

    Checklist of differential diagnoses of DILI and HILI. This tabular listing, although not comprehensive, is to be used as a guide and in connection with the updated RUCAM, derived from a previous publication.

    Differential DiagnosisDiagnostic ParametersDiagnostic Exclusion Done for Patient’s Assessment  
      YesNoPartial
    ●   Hepatitis A virus (HAV)Anti-HAV-IgM□□□
    ●   Hepatitis B virus (HBV)HBV-DNA, anti-HBc-IgM□□□
    ●   Hepatitis C virus (HCV)HCV-RNA, anti-HCV□□□
    ●   Hepatitis E virus (HEV)HEV-RNA, titer change for anti-HEV-IgM/anti-HEV-IgG□□□
    ●   Cytomegalovirus (CMV)CMV-PCR, titer change for anti-CMV-IgM/anti-CMV-IgG□□□
    ●   Epstein Barr virus (EBV)EBV-PCR, titer change for anti-EBV-IgM/anti-EBV-IgG□□□
    ●   Herpes simplex virus (HSV)HSV-PCR, titer change for anti-HSV-IgM/anti-HSV-IgG□□□
    ●   Varicella zoster virus (VZV)VZV-PCR, titer change for anti-VZV-IgM/anti-VZV-IgG□□□
    ●   Other virus infectionsSpecific serology of Adenovirus, Coxsackie-B-Virus, Echovirus, Measles virus, Rubella virus, Flavivirus, Arenavirus, Filovirus, Parvovirus, HIV, and others□□□
    ●   Other infectious diseasesSpecific assessment of bacteria, fungi, parasites, worms, and others□□□
    ●   Autoimmune hepatitis (AIH) type IGamma globulins, ANA, SMA, AAA, SLA/LP, Anti-LSP, Anti-ASGPR□□□
    ●   Autoimmune hepatitis (AIH) type IIGamma globulins, Anti-LKM-1 (CYP 2D6), Anti-LKM-2 (CYP 2C9), Anti-LKM-3□□□
    ●   Primary biliary cholangitis (PBC)AMA, Anti PDH-E2□□□
    ●   Primary sclerosing cholangitis (PSC)p-ANCA, MRC□□□
    ●   Autoimmune cholangitis (AIC)ANA, SMA□□□
    ●   Overlap syndromesSee AIH, PBC, PSC, and AIC□□□
    ●   Non alcoholic steatohepatitis (NASH)BMI, insulin resistance, hepatomegaly, echogenicity of the liver□□□
    ●   Alcoholic liver disease (ALD)Patient’s history, clinical and laboratory assessment, other alcoholic disease(s)□□□
    ●   Drug induced liver injury (DILI) or herb induced liver injury (HILI)Patient’s history, clinical and laboratory assessment, sonography, use of the updated RUCAM□□□
    ●   Cocaine, ecstasy and other amphetaminesToxin screening□□□
    ●   Rare intoxicationsToxin screening for household and occupational toxins□□□
    ●   Hereditary hemochromatosisSerum ferritin, total iron-binding capacity, genotyping for C2824 and H63D mutation, hepatic iron content□□□
    ●   Wilson diseaseCopper excretion (24 h urine), ceruloplasmin in serum, free copper in serum, Coombs-negative hemolytic anemia, hepatic copper content, Kayser-Fleischer-ring, neurologic-psychiatric work-up, genotyping□□□
    ●   PorphyriaPorphobilinogen in urine, total porphyrines in urine□□□
    ●   α1—Antitrypsin deficiencyα1—Antitrypsin in serum□□□
    ●   Biliary diseasesClinical and laboratory assessment, hepatobiliary sonography, MRC□□□
    ●   Pancreatic diseasesClinical and laboratory assessment, sonography, CT, MRT□□□
    ●   Celiac diseaseTTG antibodies, endomysium antibodies, duodenal biopsy□□□
    ●   Anorexia nervosaClinical context□□□
    ●   Parenteral nutritionClinical context□□□
    ●   Cardiopulmonary diseasesCardiopulmonary assessment of congestive heart disease, myocardial infarction, cardiomyopathy, cardiac valvular dysfunction, pulmonary embolism, pericardial diseases, arrhythmia, hemorrhagic shock, and various other conditions□□□
    ●   Addison’s diseasePlasma cortisol□□□
    ●   Thyroid diseasesTSH basal, T4, T3□□□
    ●   Grand mal seizuresClinical context of epileptic seizure (duration > 30 min)□□□
    ●   Heat strokeShock, hyperthermia□□□
    ●   PolytraumaShock, liver injury□□□
    ●   Systemic diseasesSpecific assessment of sarcoidosis, amyloidosis, metastatic tumor, sepsis, and others□□□
    ●   Other diseasesClinical context□□□
    Abbreviations: AAA, Anti-actin antibodies; AMA, Antimitochondrial antibodies; ANA, Antinuclear antibodies; ASGPR, Asialo-glycoprotein-receptor; BMI, Body mass index; CT, Computed tomography; CYP, Cytochrome P450; PDH, Pyruvate dehydrogenase; HAV, Hepatitis A virus; HBc, Hepatitis B core; HBV, Hepatitis B virus; HCV, Hepatitis C virus; HEV, Hepatitis E virus; HILI, Herb induced liver injury; HIV; human immunodeficiency virus; LKM, Liver kidney microsomes; LP, Liver-pancreas antigen; LSP, Liver specific protein; MRC, Magnetic resonance cholangiography; MRT, Magnetic resonance tomography; p-ANCA, Perinuclear antineutrophil cytoplasmic antibodies; PCR, Polymerase chain reaction; RUCAM, Roussel Uclaf Causality Assessment Method; SLA, Soluble liver antigen; SMA, Smooth muscle antibodies; TSH, Thyroid stimulating hormone; TTG, Tissue transglutaminase


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    Abbreviations: AAA, Anti-actin antibodies; AMA, Antimitochondrial antibodies; ANA, Antinuclear antibodies; ASGPR, Asialo-glycoprotein-receptor; BMI, Body mass index; CT, Computed tomography; CYP, Cytochrome P450; PDH, Pyruvate dehydrogenase; HAV, Hepatitis A virus; HBc, Hepatitis B core; HBV, Hepatitis B virus; HCV, Hepatitis C virus; HEV, Hepatitis E virus; HILI, Herb induced liver injury; HIV; human immunodeficiency virus; LKM, Liver kidney microsomes; LP, Liver-pancreas antigen; LSP, Liver specific protein; MRC, Magnetic resonance cholangiography; MRT, Magnetic resonance tomography; p-ANCA, Perinuclear antineutrophil cytoplasmic antibodies; PCR, Polymerase chain reaction; RUCAM, Roussel Uclaf Causality Assessment Method; SLA, Soluble liver antigen; SMA, Smooth muscle antibodies; TSH, Thyroid stimulating hormone; TTG, Tissue transglutaminase

    Differential Diagnosis / Diagnostic Parameters


    Thus, the updated RUCAM can be used based on:

    • Type of the damage to the liver (hepatocellular, cholestatic, mixed type);
    • Detailing of the main elements of assessments (table hepatocellular, cholestatic/mixed type of damage);
    • Differential diagnosis (checklist table)
    • Reexposure criteria (table).

    Correct Diagnoses

    Results based on the updated RUCAM are quickly available for trained physicians with substantial clinical experience who then have to decide whether DILI or HILI is the most like diagnosis in their patients or any other differential diagnoses. Their decision is crucial, as DILI and HILI require discontinuation of the offending product whereas other diagnoses may require specific therapeutic modalities. The patient will immediately profit from the correct diagnosis achieved after using the updated RUCAM and the checklist.

    Missed Diagnoses

    Unrecognized alternative causes to the liver injury are a real clinical problem when caring for patients with initially assumed but later not confirmed DILI or HILI; the long list of missed diagnoses in the setting of initially assumed injury cases is indeed threatening. More recent evidence suggests that the problem of missed diagnoses is multifaceted and caused by incomplete case data collection, poor case data analysis, problems of appropriate case data transfer from medical files to the manuscript, and unjustified upgrading of causality scores. Missing the correct diagnosis may cause legal considerations that are better avoided by prior sophisticated clinical and regulatory approaches. Effective treatments would have been available for some patients with missed diagnoses, a critical situation in the clinical context.

    Abbreviations: CMV, Cytomegalovirus; EBV, Epstein Barr virus; HSV Herpes simplex virus; LKM, Liver kidney microsomes; SMA, Smooth muscle antibodies; VZV, Varicella zoster virus.

    Missed diagnoses in cases of initially suspected hepatotoxicity by synthetic drugs or herbs. Adapted from previous reports, which provide the respective references for each missed diagnosis listed above.

    Historical background

    Previous synonym of RUCAM were CIOMS (Council for International Organizations of Medical Sciences) or CIOMS/RUCCAM.

    The updated RUCAM is as good as physicians and assessors are handling this method and consider basic liver tests for the liver injury classification, the specific operational information, details of core elements and their scoring, differential diagnoses, and the reexposure criteria. RUCAM has not been designed for chronic DILI and HILI or when a suspected injury occurs on pre-existing liver disease, both complex conditions where an expert panel of hepatologists would provide a more accurate approach especially for the timing of the events and the exclusion of alternative causes.

    Historical background and the original work confirm the use of RUCAM as single term for future cases, dismissing now the term CIOMS for reasons of simplicity and clarity. RUCAM represents a structured, standardized, validated, and hepatotoxicity specific diagnostic approach that attributes scores to individual key items, providing final quantitative gradings of causality for each suspect drug/herb in a case report.

    Experts from Europe and the United States had previously established in consensus meetings the first criteria of RUCAM to meet the requirements of clinicians and practitioners in care for their patients with suspected DILI and HILI. RUCAM was completed by additional criteria and validated, assisting to establish the timely diagnosis with a high degree of certainty. In many countries and for more than two decades, physicians, regulatory agencies, case report authors, and pharmaceutical companies successfully applied RUCAM for suspected DILI and HILI. Their practical experience, emerging new data on DILI and HILI characteristics, and few ambiguous questions in domains such alcohol use and exclusions of non-drug causes led to the present update of RUCAM. The aim was to reduce interobserver and intraobserver variability, to provide accurately defined, objective core elements, and to simplify the handling of the items. The authors presented the update of the well accepted original RUCAM scale and recommend its use for clinical, regulatory, publication, and expert purposes to validly establish causality in cases of suspected DILI and HILI, facilitating a straightforward application and an internationally harmonized approach of causality assessment as a common basic tool.

    RUCAM was not designed for chronic DILI and HILI, or when damage is suspected in pre-existing liver disease.

    RUCAM scoring can help establish a clinical diagnosis, which can be useful for further choice of therapy.


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     Literature

    1. Danan G., Bénichou C. Causality assessment of adverse reactions to drugs—I. A novel method based on the conclusions of international consensus meetings: Application to drug-induced liver injuries. J. Clin. Epidemiol. 1993;46:1323–1330. doi: 10.1016/0895-4356(93)90101-6. [PubMed]
    2. Andrade RJ, Robles M, Fernández-Castañer A, López-Ortega S, López-Vega MC, Lucena MI (2007).
      “Assessment of drug-induced hepatotoxicity in clinical practice: a challenge for gastroenterologists.” World J. Gastroenterol. 13 (3): 329–40.
    3. Danan G, Teschke R. RUCAM in Drug and Herb Induced Liver Injury: The Update. Int J Mol Sci. 2015;17(1):14. Published 2015 Dec 24. doi:10.3390/ijms17010014
    4. Teschke R., Eickhoff A., Schwarzenboeck A., Schmidt-Taenzer W., Genthner A., Frenzel C., Wolff A., Schulze J. Clinical review: Herbal hepatotoxicity and the call for systematic data documentation of individual cases. J. Liver Clin. Res. 2015;2:1008. (Google Scholar)

    See also:

    Child-Pugh Score for Cirrhosis Mortality: online calculator
    King’s College Criteria for Non- Acetaminophen Toxicity acute hepatic failure
    King’s College Criteria for Acetaminophen Toxicity

    Сообщение RUCAM scale to estimate the probability of the drug-induced liver injury (DILI) and herb induced liver injury (HILI) online calculator появились сначала на ClinCaseQuest.

    ]]>         The Hamilton Anxiety Rating Scale (HAM-A/HARS) online calculator https://clincasequest.hospital/ham-ahars/ Fri, 21 Jan 2022 07:10:54 +0000 https://clincasequest.hospital/?p=32908 The Hamilton Anxiety Rating Scale evaluates anxiety levels based on clinical questions, quantifies the severity of anxiety syndrome, and is often used to evaluate antipsychotic…

    Сообщение The Hamilton Anxiety Rating Scale (HAM-A/HARS) online calculator появились сначала на ClinCaseQuest.

    ]]>     The Hamilton Anxiety Rating Scale evaluates anxiety levels based on clinical questions, quantifies the severity of anxiety syndrome, and is often used to evaluate antipsychotic drugs.

    It consists of 14 indicators, each of which is defined by several symptoms. Each indicator is rated on a 5-point scale from 0 (none) to 4 (severe). The Hamilton Anxiety Scale can help objectify and rate the severity of a patient’s anxiety.

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    Points total 0
    * Required

    The Hamilton Anxiety Scale can help objectify and assess the severity of a patient’s anxiety.

    Each parameter is assessed according to the level of severity:

    Point Values:

    0=Not Present
    +1=Mild
    +2=Moderate
    +3=Severe
    +4=Very Severe

    To assess the Hamilton anxiety scale, it is necessary to add the selected points.

    1. Anxious mood: Worries, anticipation of the worst, fearful anticipation, irritability.Not Present0
     Mild+1
     Moderate+2
     Severe+3
     Very Severe+4
    2. Tension: Feelings of tension, fatigability, startle response, moved to tears easily, trembling, feelings of restlessness, inability to relax.Not Present0
     Mild+1
     Moderate+2
     Severe+3
     Very Severe+4
    3. Fears: Of dark, of strangers, of being left alone, of animals, of traffic, of crowds.Not Present0
     Mild+1
     Moderate+2
     Severe+3
     Very Severe+4
    4. Insomnia: Difficulty in falling asleep, broken sleep, unsatisfying sleep and fatigue on waking, dreams, nightmares, night terrors.Not Present0
     Mild+1
     Moderate+2
     Severe+3
     Very Severe+4
    5.  Intellectual: Difficulty in concentration, poor memory.Not Present0
     Mild+1
     Moderate+2
     Severe+3
     Very Severe+4
    6. Depressed mood: Loss of interest, lack of pleasure in hobbies, depression, early waking, diurnal swing.Not Present0
     Mild+1
     Moderate+2
     Severe+3
     Very Severe+4
    7. Somatic (muscular): Pains and aches, twitching, stiffness, myoclonic jerks, grinding of teeth, unsteady voice, increased muscular tone.Not Present0
     Mild+1
     Moderate+2
     Severe+3
     Very Severe+4
    8. Somatic (sensory): Tinnitus, blurring of vision, hot and cold flushes, feelings of weakness, pricking sensation.Not Present0
     Mild+1
     Moderate+2
     Severe+3
     Very Severe+4
    9. Cardiovascular symptoms: Tachycardia, palpitations, pain in chest, throbbing of vessels, fainting feelings, missing beat.Not Present0
     Mild+1
     Moderate+2
     Severe+3
     Very Severe+4
    10 . Respiratory symptoms: Pressure or constriction in chest, choking feelings, sighing, dyspnea.Not Present0
     Mild+1
     Moderate+2
     Severe+3
     Very Severe+4
    11. Gastrointestinal symptoms: Difficulty in swallowing, wind abdominal pain, burning sensations, abdominal fullness, nausea, vomiting, borborygmi, looseness of bowels, loss of weight, constipation.Not Present0
     Mild+1
     Moderate+2
     Severe+3
     Very Severe+4
    12. Genitourinary symptoms: Frequency of micturition, urgency of micturition, amenorrhea, menorrhagia, development of frigidity, premature ejaculation,loss of libido, impotence.Not Present0
     Mild+1
     Moderate+2
     Severe+3
     Very Severe+4
    13. Autonomic symptoms: Dry mouth, flushing, pallor, tendency to sweat, giddiness, tension headache, raising of hair.Not Present0
     Mild+1
     Moderate+2
     Severe+3
     Very Severe+4
    14. Behavior at interview: Fidgeting, restlessness or pacing, tremor of hands, furrowed brow, strained face, sighing or rapid respiration, facial pallor, swallowing, etc.Not Present0
     Mild+1
     Moderate+2
     Severe+3
     Very Severe+4

    Score interpretation:

    • Scores ≤17 indicate mild anxiety severity.
    • Scores of 18-24 indicate mild to moderate anxiety severity
    • Scores of 25-30 indicate moderate to severe anxiety severity
    • Scores >30 indicate severe anxiety

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    Literature:

    1. Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol 1959; 32:50–55 https://pubmed.ncbi.nlm.nih.gov/13638508/
    2. Maier W, Buller R, Philipp M, Heuser I. The Hamilton Anxiety Scale: reliability, validity and sensitivity to change in anxiety and depressive disorders. J Affect Disord 1988;14(1):61–8 https://pubmed.ncbi.nlm.nih.gov/2963053/  Per Bech. Measuring States of
    3. Anxiety with Clinician-Rated and Patient-Rated Scales, Different Views of Anxiety Disorders. 2011, DOI: 10.5772/21246 https://www.intechopen.com/books/different-views-of-anxiety-disorders/measuring-states-of-anxiety-with-clinician-rated-and-patient-rated-scales

    Charlson Comorbidity Index (CCI) Online Calculator

    Charlson Comorbidity Index predicts 10-year survival in patients with multiple comorbidities.

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    History of definite or probable MI (EKG changes and/or enzyme changes)

    Exertional or paroxysmal nocturnal dyspnea and has responded to digitalis, diuretics, or afterload reducing agents

    Intermittent claudication or past bypass for chronic arterial insufficiency, history of gangrene or acute arterial insufficiency, or untreated thoracic or abdominal aneurysm (≥6 cm)

    History of a cerebrovascular accident with minor or no residua and transient ischemic attacks

    Chronic cognitive deficit

    Any history of treatment for ulcer disease or history of ulcer bleeding

    Severe = cirrhosis and portal hypertension with variceal bleeding history, moderate = cirrhosis and portal hypertension but no variceal bleeding history, mild = chronic hepatitis (or cirrhosis without portal hypertension)

    Severe = on dialysis, status post kidney transplant, uremia, moderate = creatinine >3 mg/dL (0.27 mmol/L)

    * Required
    VariablePointsAge <50…
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    Multiple Myeloma Diagnostic Criteria – Online Calculator

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    ≥1 of the following (A or B)

    ≥1 myeloma defining event (C1 or C2)

    * Required
    For Multiple Myeloma Diagnostic Criteria assessment necessary to provide selection of the…
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    Сообщение The Hamilton Anxiety Rating Scale (HAM-A/HARS) online calculator появились сначала на ClinCaseQuest.

    ]]>         R-value for Liver Injury Online calculator https://clincasequest.hospital/r-value/ Wed, 19 Jan 2022 14:30:28 +0000 https://clincasequest.hospital/?p=32873 Can be used in patients with suspected drug induced liver injury (DILI) with abnormal liver chemistries. R-value= (patient’s ALT / upper limit of normal ALT…

    Сообщение R-value for Liver Injury Online calculator появились сначала на ClinCaseQuest.

    ]]>     Can be used in patients with suspected drug induced liver injury (DILI) with abnormal liver chemistries.

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    According to your lab

    According to your lab

    * Required

    R-value= (patient’s ALT / upper limit of normal ALT ) / ( patient’s ALP / upper limit of normal ALP )

    Note: Normal values may vary by lab.

    • R-value calculation allows clinicians to collectively identify and describe the pattern of liver injury in an objective manner.
    • R-value calculation allows clinicians suspecting a diagnosis of DILI to formulate an organized diagnostic strategy to rule out other causes of acute liver injury and to narrow the list of possible culprit drugs based on the pattern of liver injury.
    • Recommended by guidelines.

    Parameters that required for the assessment:

    • Patient’s ALT, U/L
    • Upper limit of normal ALT According to your lab, U/L
    • Patient’s ALP, U/L
    • Upper limit of normal ALP According to your lab, U/L

    Interpretation:

    R-value rangeThe type of the liver injury  Conclusion and Advise
    <2 Cholestatic pattern of liver injury.  • Pancreatic malignancy, cholangiocarcinoma, primary malignancy of the gallbladder, choledocholithiasis, sepsis, TPN, heart failure, PSC, and PBC should be ruled out as causes
    • Commonly used drugs that can cause this pattern of liver injury include: amoxicillin/clavulanate, trimethoprim/sulfamethoxazole, azathioprine, and anabolic steroids
    • Recommend imaging studies (e.g. abdominal ultrasound)
    2-5Mixed pattern of liver injury.  Recommend acute viral hepatitis serologies, HCV RNA and autoimmune hepatitis serologies, imaging studies (e.g. abdominal ultrasound)
    >5Hepatocellular pattern of liver injury.  • Acute viral hepatitis, ischemic liver injury, Budd-Chiari syndrome, autoimmune hepatitis, and Wilson’s disease (in younger patients) should be ruled out as causes
    • Commonly used drugs that can cause this pattern of liver injury include: isoniazid, macrolides, nitrofurantoin, minocycline, anti-epileptics, NSAIDs, green tea extract, and inhaled anesthetics
    • Recommend acute viral hepatitis serologies, HCV RNA and autoimmune hepatitis serologies, imaging studies (e.g. abdominal ultrasound)

    Futher diagnostic approach:

    R FactorInjury typeRecommended 1st line tests*
    >5HepatocellularAcute viral hepatitis serologies, HCV RNA and autoimmune hepatitis serologies, imaging studies (e.g. abdominal ultrasound)
    2–5MixedAcute viral hepatitis serologies, HCV RNA and autoimmune hepatitis serologies, imaging studies (e.g. abdominal ultrasound)
    <2CholestaticImaging studies (e.g. abdominal ultrasound)

    *From Chalasani 2014

    The R-value (also known as the R ratio or R factor) was introduced after an international consensus meeting in 1989 aimed at preparing definitions and criteria related to drug related liver injury. At the request of the Council for International Organizations of Medical Sciences (CIOMS), a pilot program led by pharmaceutical company Roussel Uclaf was initiated to help classify different patterns of acute liver injury, introducing the R-value.

    The R-value itself has not been validated, but remains commonly used in clinical practice to objectively define different patterns of liver injury. The American College of Gastroenterology (ACG) has incorporated the R-value in its guidelines for diagnosis and management of idiosyncratic drug-induced liver injury.

    Recommendations for workup based on R Factor, adapted from Chalasani 2014

    • The pattern of acute liver injury (and therefore the R-value) can vary throughout the clinical course of the illness.
    • Identifying the pattern of liver injury can guide diagnostic approach to DILI, including appropriate further diagnostic testing necessary to rule out other causes of liver injury.
    • Calculating the R-value is the first step in calculating the Roussel Uclaf Causality Assessment Method (RUCAM) when determining if liver injury is related to a specific drug.
    • Because the pattern of liver injury can evolve over time, the time point at which liver chemistries are used to calculate the R-value  can alter the final result. It is recommended that the initial liver chemistries suggesting liver injury be used, but ultimately left to the clinician to decide what set of liver chemistries to use when making an assessment.
    • The use of upper limit of normal (ULN) in the equation creates some room for variability. The ULN varies among different laboratories.
    • While not validated, the R-value is widely used and has been incorporated into guideline recommendations for assessing liver injury.
    • Though the R Factor does not incorporate coagulopathy (INR) and mental status, these two factors should always be immediately assessed in all cases of acute liver injury to rule out acute liver failure.

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    Literature

    1. Bénichou C. Criteria of drug-induced liver disorders. Report of an international consensus meeting. J Hepatol. 1990 Sep;11(2):272-6. doi: 10.1016/0168-8278(90)90124-a. PMID: 2254635.
    2. Chalasani NP, Hayashi PH, Bonkovsky HL, Navarro VJ, Lee WM, Fontana RJ; Practice Parameters Committee of the American College of Gastroenterology. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2014 Jul;109(7):950-66; quiz 967. doi: 10.1038/ajg.2014.131. Epub 2014 Jun 17. PMID: 24935270.
    3. Danan G, Teschke R. RUCAM in Drug and Herb Induced Liver Injury: The Update. Int J Mol Sci. 2015;17(1):14. Published 2015 Dec 24. doi:10.3390/ijms17010014

    Сообщение R-value for Liver Injury Online calculator появились сначала на ClinCaseQuest.

    ]]>         Counseling a patient who is taking warfarin / OSCE guide https://clincasequest.hospital/counseling-a-patient-who-is-taking-warfarin-osce-guide/ Wed, 12 Jan 2022 13:05:31 +0000 https://clincasequest.hospital/?p=32637 Before initiating anticoagulation therapy with warfarin Before initiating anticoagulation therapy an assessment of the patient’s coagulation status is necessary, including: All these results should be…

    Сообщение Counseling a patient who is taking warfarin / OSCE guide появились сначала на ClinCaseQuest.

    ]]>     Before initiating anticoagulation therapy with warfarin

    Before initiating anticoagulation therapy an assessment of the patient’s coagulation status is necessary, including:

    • a baseline INR
    • indication for treatment
    • apropriate INR target range
    • proposed duration of treatment

    All these results should be recorded in the patient’s case records and oral anticoagulation therapy booklet.

    Before Counselling

    Before Counselling physician should review the patient’s medical background to establish the current indication for warfarin and the patient’s target INR range.

    Before adjusting the dose during maintaining treatment

    Before adjusting the dose of warfarin the physician should review:

    • the previous doses warfarin
    • earlier INR results
    • any changes in the patient’s clinical condition
    • any changes in medication
    • any changes in lifestyle
    • alcohol consumption

    Target INR ranges

    The most common target INR is 2.5. Others are:

    Recurrent VTE (DVT or PE) despite adequate anticoagulation3.5
    CardioversionPre – 3.0 Post – 2.5*
    Mechanical Heart ValvesSee below

    *The 2016 European Society of Cardiology (ESC) guidelines on cardioversion state that patients who have been in AF for longer than 48 hours should start OAC therapy at least 3 weeks before cardioversion and continue for 4 weeks afterwards (in those without a need for long-term anticoagulation).

    Atrial fibrillation Anticoagulation is normally offered to patients with a CHADSVASc score ≥ 2 and considered in men with a CHADSVASc score of 1.

    Warfarin is not usually indicated for ischaemic stroke without atrial fibrillation (except in antiphospholipid syndrome), retinal vessel occlusion, peripheral artery thrombosis, coronary artery graft or coronary angioplasty, and stents.

    Cardioversion

    Anticoagulation for 4 weeks before and for 3 months afterward. To minimize cardioversion cancellations due to low INRs on the day of the procedure we recommend a target INR of 3.0 prior to the procedure and 2.5 afterward (Oxford guidelines).

    *The 2016 European Society of Cardiology (ESC) guidelines on cardioversion state that patients who have been in AF for longer than 48 hours should start OAC therapy at least 3 weeks before cardioversion and continue for 4 weeks afterwards (in those without a need for long-term anticoagulation).

    Mechanical Heart Valves.  Target INR range based on indications

    Target INR in mechanical heart valve replacement Mechanical Prosthesis thrombogenicity*Isolated Aortic Valve ReplacementMitral or Tricuspid Valve Replacement, or
     No risk factors**AVR with Risk factors **
    Low (most current valves)2.53.0
    Medium3.03.5
    High3.53.5***

    *Prosthesis thrombogenicity:

    • Low: Carbomedics (aortic position), Medtronic Hall, St Jude Medical (without silzone)
    • Medium: Bjork-Shiley, other bileaflet valves
    • High: Starr-Edwards, Omniscience, Lillehei-Kaster.

    **Patient-related risk factors for thrombosis:

    • Mitral, tricuspid or pulmonary position
    • Previous arterial thromboembolism
    • Atrial fibrillation
    • Left atrium diameter >50 mm
    • Mitral stenosis of any degree
    • Left ventricular ejection fraction< 35%.

    ***Was 4.0 in ESC guideline

    Counseling steps:

    • Opening the consultation
      • Wash your hands and don PPE if appropriate
      • Introduce yourself to the patient including your name and role
      • Confirm the patient’s name and date of birth
      • Explain the reason for the consultation
    • Ideas, concerns and expectations
      • Explore what the patient currently understands about warfarin and why they are being prescribed it
      • Ask if the patient has any concerns about warfarin
      • Explore what the patient is hoping to get out of the consultation
    • How warfarin works
      • Explain that warfarin works by thinning the blood
      • Explain what warfarin can be used to treat
      • Explain that the action of warfarin can be reversed with an antidote if needed
    • INR
      • Explain what INR is
      • Explain what the patient’s target INR range is
      • Explain how INR is monitored
    • How to take warfarin
      • Explain that warfarin should be taken at the same time each day
      • Explain the different types of warfarin tablets
      • Explain what the patient should do if they forget a dose
      • Advise the patient to let medical professionals know that they take warfarin when they are being prescribed new medications
      • Advise the patient to let the team managing their anticoagulation know when they start taking a new medication
      • Advise the patient about the importance of effective contraception if taking warfarin (if relevant)
    • Bleeding whilst taking warfarin
      • Explain that the main side effect of warfarin is bleeding more easily than normal
      • Explain the common types of ‘less serious bleeding’ and what to do if they experience them
      • Explain the rarer types of ‘serious bleeding’ and what to do if they experience them
    • Other side effects of warfarin
      • Explain the common side effects of warfarin (other than bleeding)
      • Explain the rarer and more serious side effects of warfarin
    • Lifestyle advice
      • Advise the patient about the impact of diet on the effect of warfarin
      • Advise the patient about the impact of alcohol on the effect of warfarin
      • Advise the patient about brushing teeth, shaving and dental procedures
    • Yellow booklets and alert card
      • Provide the patient with information about the INR monitoring booklet and patient information booklet
      • Explain the importance of carrying the anticoagulant alert card with them at all times
    • Closing the consultation
      • Summarise the key points back to the patient
      • Ask the patient if they have any questions or concerns that have not been addressed
      • Arrange appropriate follow-up
      • Thank the patient for their time
      • Dispose of PPE appropriately and wash your hands
    • Key communication skills
      • Active listening
      • Summarising
      • Signposting

    Join our Simulation Training to gain clinical experience

    Opening the consultation

    1. Wash your hands and don PPE if appropriate.
    2. Introduce yourself to the patient including your name and role.
    3. Confirm the patient’s name and date of birth.
    4. Explain the reason for the consultation

    Ideas, concerns and expectations

    1. Explore what the patient currently understands about warfarin and why they are being prescribed it
    2. Ask if the patient has any concerns about warfarin
    3. Explore what the patient is hoping to get out of the consultation
    IdeasExplore what the patient currently understands about warfarin and why they are being prescribed it“Have you heard of warfarin?”
    “What do you already know about warfarin?”
    “Do you know why people take warfarin?”
    Concerns  Ask if the patient has any concerns about warfarin“Is there anything that worries you about taking warfarin?”
    Expectations  Explore what the patient is hoping to get out of the consultation  “What were you hoping we’d discuss today?”

    How warfarin works

    1. Explain that warfarin works by thinning the blood
    2. Explain what warfarin can be used to treat
    3. Explain that the action of warfarin can be reversed with an antidote if needed

    Using patient-friendly language, explain how warfarin works.

    “Warfarin is a medication that helps “thin” your blood to decrease your body’s chance of forming harmful clots. Unwanted blood clots may cause strokes, heart attacks, or other potentially harmful events such as clots in the legs (deep vein thrombosis) or lungs (pulmonary embolism).”

     “Warfarin is a type of medicine known as an anticoagulant. It helps to thin the blood, making it less likely that a dangerous blood clot could form.”

    “Warfarin can be used to treat people who have a previous blood clot in the leg or lungs. It can also be used to prevent future blood clots in people who are at high risk of having them in the future, such as people with an irregular heartbeat or an artificial heart valve.”

    “There are proteins in your blood to help form clots. These proteins are made by your liver with the help of vitamin K. Warfarin works by blocking the effects of vitamin K, making it harder for your body to form clots. In order to make sure the amount of warfarin you’re taking is right for you, your healthcare professional will test your blood periodically.”

    “The action of warfarin can be rapidly reversed with an antidote in situations where we need to reduce the risk of bleeding.”

    “Following the administration of warfarin an observable anticoagulation effect is delayed. The delay may range from two to seven days because warfarin does not act directly on the inactive clotting factors already in circulation but on the rate of synthesis of new factors by the liver. “

    INR

    1. Explain what INR is
    2. Explain what the patient’s target INR range is
    3. Explain how INR is monitored

    Explain the role of INR in monitoring the effect of warfarin.

    “The INR is a measure of how long it takes blood to clot. In healthy people an INR of 1 is normal. Since you are at a higher risk for blood clots we want your blood to be thinner than normal and therefore take longer to clot. As a result, the target range for your INR would be between 2-3, meaning it takes two to three times as long for your blood to clot compared to someone not taking warfarin.”

    “In order to ensure that we keep your blood within the necessary range we will need to monitor your INR level every so often; this is done through a blood test. The blood tests will initially be frequent (every 3-4 days until two consecutive readings are within range), and then after this, you will be tested twice weekly for 1-2 weeks (again until two consecutive readings within range). Thereafter, testing can increase to longer periods (e.g. every 12 weeks). Your dose of warfarin will be adjusted based on the INR results with the aim of keeping it within the target range.”

    Frequency of monitoring

    During the induction and initial stabilization of patients on warfarin, daily INR measurements are often necessary, particularly with the more aggressive induction regimens. After initial stabilization the INR will, in most cases, dictate the frequency of monitoring.

    Weekly monitoring is advised for four to six weeks after stabilization, gradually changing to every one to two months if concordance and control are good.

    “It is very important to have your blood tests regularly (preferably in a warfarin clinic)”.

    How to take warfarin

    1. Explain that warfarin should be taken at the same time each day
    2. Explain the different types of warfarin tabletsExplain what the patient should do if they forget a dose
    3. Advise the patient to let medical professionals know that they take warfarin when they are being prescribed new medications
    4. Advise the patient to let the team managing their anticoagulation know when they start taking a new medication
    5. Advise the patient about the importance of effective contraception if taking warfarin (if relevant)

    Key points to communicate when discussing warfarin use:

    • “Warfarin should be taken at the same time each day to keep the levels of warfarin steady.”
    • “Tablets have different colours depending on their strength (e.g. 0.5mg white; 1mg brown; 3mg blue; 5mg pink).”
    • “If you forget to take a dose you should take it as soon as you remember, but if you don’t remember till the following day you should skip the missed dose. You should never take two doses together to make up for a missed dose and you should inform your doctor or warfarin clinic about any missed doses at your next appointment.”
    • “Whenever you are going to purchase or be prescribed a new medication you should let the doctor or pharmacist know that you take warfarin so they can avoid prescribing medications which alter your warfarin level.”
    • “When you start taking a new medication you should let your doctor or anticoagulant clinic know so that they can consider if your warfarin levels need monitoring more frequently.”
    • “You should continue to take your warfarin tablets regularly until you have been told to stop.”
    • “Warfarin is not safe to be used during pregnancy and therefore you should have an effective contraceptive method in place before you start taking warfarin.”
    • “You must inform anticoagulant healthcare staff if you think you have taken too much warfarin or have missed any doses.”
    • “You must inform the relevant healthcare professionals if you start, stop or change the dose of your medicines, or if your diet changes substantially (eg. intake of broccoli, lettuce or spinach /)”Other medicines” include not only prescribed drugs but also products that may be brought without prescription, such as aspirin,  and medicines containing aspirin, vitamins, food supplements and herbal or homoeopathic remedies.”
    • “If you require surgery, dental work, or any other invasive procedure you may need stop taking warfarin temporarily. You should discuss your warfarin management with a healthcare professional prior to the procedure”.

    Selected examples of drug interactions with warfarin:

    Drugs that enhance the anticoagulant effectDrugs that reduce the anticoagulant effect
    Allopurinol
    Amiodarone
    Aspirin
    Azole antifungals (fluconazole, itraconazole, ketconazole, miconazole) Cimetidine
    Ciprofloxacin
    Entacapone
    Fibrates
    Fluvastatin
    Metronidazole
    Omeprazole
    Simvastatin
    Tamoxifen
    Testosterone
    Tetracyclines
    Thyroxine
    Tramadol
    SSRIs    		Carbamazepine
    Oestrogens
    Phenytoin*
    Primidone
    Progestogens
    Rifamycins
    Vitamin K present in some enteral feeds  

    * The metabolism of coumarins is accelerated by phenytoin (there is a possibility of a reduced anticoagulant effect, but enhancement has also been reported).

    Erythromycin and other macrolides interact with warfarin unpredictably and only affect certain individuals.

    Surgery and warfarin therapy

    When a patient who is receiving long-term warfarin therapy requires surgery a variety of approaches may be considered.

    • If the risk f subsequent thromboembolism is low it may be acceptable to discontinue the warfarin in advance of the procedure.
      • For patients with a greater risk, the dose may be lowered and the operation performed when the INR is at an acceptable level (ie., below 2.5).
      • A third alternative is to reduce the anticoagulant effect with vitamin K just prior to the surgery and operate under prophylactic cover of heparin, with the aim of reintroducing in the immediate post-operative period.

    Dental advice

    Many dentists appear to be unaware of the specific needs of the patients who are receiving anticoagulants and perform procedures from dental hygiene to multiple extractions without managing the treatment or referring to others.

    Minor dental surgical procedures can be carried out safely as long as the patient’s INR is below 4.0. Examples of the procedures likely to be carried out in primary care would be the simple extraction of up to the three teeth, crown work, and cosmetic dentistry. An INR measurement should be taken within 72 hours of the procedure.

    Pharmaceutical advice for patients on the management of clots in the post-operative dental period:

    The physician should advise the patient to:

    • rest while the local anesthetic wears off and the clot fully forms (this usually takes two to three hours)
      • take paracetamol if pain control is needed (NSAIDs and aspirin or products containing these medicines should be avoided)
      • avoid rinsing the mouth for 24 hours unless specifically advised to do so by a healthcare professional
      • avoid sucking hard or disturbing the clot with the tongue or anything else
      • avoid hot liquids and hard foods for the rest of the day
      • avoid chewing on the affected side until they are sure that a stable clot has formed
      • rinse the mouth with warm salty water three or four times the day after treatment

    If the bleeding continues or restarts you should advise the patient to apply pressure over the bleeding area using a clean, damp folded handkerchief or gauze pad. The pad should be placed over the site of the bleeding and the patient should bite down firmly for 20 minutes while sitting quietly in a chair.

    Bleeding whilst on warfarin

    1. Explain that the main side effect of warfarin is bleeding more easily than normal
    2. Explain the common types of ‘less serious bleeding’ and what to do if they experience them
    3. Explain the rarer types of ‘serious bleeding’ and what to do if they experience them

    The main side effect of warfarin involves bleeding more easily than normal (e.g. epistaxis, bleeding gums, heavier periods, bruising). These side effects most commonly occur in the first few weeks of treatment or when the patient is unwell. It is important to discuss the different types of bleeding the patient may experience and inform them what to do in these situations.

    Less serious bleeding Minor bleedingSerious bleeding Major bleeding
    “It is normal to bleed more easily when taking warfarin as the medication works by thinning the blood.

    Common types of bleeding include
    – periods that are heavier and last longer than normal
    – bleeding for a little longer than usual if you cut yourself
    – occasional nosebleeds (that last for less than 10 minutes)
    – bleeding from your gums when you brush your teeth
    – bruised that come up more easily and take longer to fade than usual.

    This type of bleeding is not dangerous and should stop by itself. If it happens, keep taking the warfarin, but tell your doctor if the bleeding bothers you or does not stop.”    		“Occasionally, you can have serious bleeding from taking warfarin. This can be dangerous and needs urgent medical attention.”
    “Stop taking warfarin and call your doctor or anticoagulant clinic, or go to A&E if you experience:
    – red pee or black poo,
    – large bruises or bruises that happen for no reason,
    – nosebleeds that last longer than 10 minutes,
    – blood in your vomit or you’re coughing up blood,
    – severe headaches, fits (seizures), changes to your eyesight, numbness or tingling in your arms or legs, or feeling very tired, weak, or sick – these can be signs of bleeding in your brain
    – any bleeding from a cut or injury that will not stop or slow down”

    Other side effects of warfarin

    1. Explain the common side effects of warfarin (other than bleeding)
    2. Explain the rarer and more serious side effects of warfarin
    Common side effectsSerious side effects  
    Common side effects (other than bleeding) of warfarin include:
    – a mild rash
    – hair loss

    These side effects are typically mild and the patient should be advised to contact their doctor or pharmacist if they become bothersome.      		Serious side effects of warfarin can include:
    – jaundice
    – skin necrosis

    As a result, patients should be advised to seek urgent medical review if they develop:
    – yellowing of the skin
    – painful swollen areas of skin  

    Lifestyle advice

    1. Advise the patient about the impact of diet on the effect of warfarin
    2. Advise the patient about the impact of alcohol on the effect of warfarin
    3. Advise the patient about brushing teeth, shaving and dental procedures
    DietDrastic changes in diet, especially an increase in consumption of foods high in vitamin K (such as broccoli, kale, or spinach) can potentially affect the control of anticoagulation.

    If the patient ever wishes to significantly change their diet, they should inform the anticoagulant clinic so necessary dose adjustments and monitoring requirements can be fulfilled. “Since vitamin K and warfarin work against each other, the amount of vitamin K in your diet can change warfarin’s effects. It is important to keep your dietary intake of vitamin K consistent. Foods such as green leafy vegetables and certain oils have higher contents of vitamin K. (See the table below for a chart of vitamin K content in selected foods).

    If you DECREASE your intake of vitamin K (eat fewer foods containing vitamin K) your dose of warfarin may need to be lowered to prevent bleeding. If you INCREASE your intake of vitamin K, your dose of warfarin may need to be increased to prevent blood clots. A MAJOR change in your vitamin K intake can affect your PT/INR, but normal daily variation in the foods you eat is okay.

    You DON’T have to avoid foods that are high in vitamin K, just keep your diet consistent. You should let your healthcare professional know if there is going to be a major change in your diet, so your PT/INR can be closely monitored”

    Many people are on special diets, such as the Atkin’s or South Beach diets, to lose weight. These diets are high-protein diets and can also affect the way warfarin works in your body. Once you take a dose of warfarin, some of it binds to protein in your bloodstream. While warfarin is attached to this protein, it has no effect on your body. It’s thought that high protein diets can increase the number of proteins in your body and cause more warfarin to be bound to protein.

    This causes a DECREASE in warfarin available to prevent clots, so your warfarin dose may need to be increased. Always check with your healthcare professional before starting any special diets, so your PT/INR can be closely monitored.  

    Certain foods can also affect how your liver clears warfarin from your body, causing warfarin levels to increase or decrease. Examples include alcohol, cranberry products (e.g., juice, supplements), and possibly grapefruit or grapefruit juice. Too much alcohol, cranberry products, or grapefruit products can INCREASE warfarin’s effect and increase your risk of bleeding. Avoid or limit your intake of alcohol, cranberry products, and grapefruit or grapefruit juice.

    Make sure your healthcare professional knows if your diet contains any of these products, so your PT/INR can be closely monitored. Cranberry juice is also known to interact with warfarin and enhance its anticoagulant effect and therefore it should be avoided.    

    “People on vitamin K-rich diets should not change eating habits without at the same time reducing the warfarin dosage, because excessive anticoagulation and bleeding may occur.”  
    Alcohol  Patients should limit their alcohol intake to a maximum of one or two drinks a day and never binge drink.
    If there are major changes in alcohol consumption (e.g. the patient stops drinking, or starts drinking more) the INR can be affected.  
    “People should limit the amount of alcohol to a maximum of one or two drinks a day and never bridge drink.”
    OtherPatients should be advised to take extra care when carrying out routine tasks such as brushing teeth or shaving; a soft toothbrush or an electric razor can help. Patients should also be advised to inform their dentist that they take warfarin when booking an appointment as this may have implications for dental procedures.  

    “Other things to remember when taking warfarin In addition to foods, many prescription and over-the-counter drugs, including vitamins and herbal supplements, can affect your warfarin level. You should not start, stop, or change doses of any drugs or supplements without first talking with your healthcare professional. Try to keep a healthy, well-balanced diet and keep your vitamin K intake consistent. Take your warfarin dose around the same time each day. If you miss a dose, take it as soon as you remember. If it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Don’t double up doses without checking with your healthcare professional. Tell your healthcare professional immediately if you have unusual bleeding or bruising, black or bloody stools, blood in the urine, or stomach pain.”

    “People should avoid activities which could cause abrasion, bruising or cuts (eg., contact sports, gardening, sewing), or at least use protection.”

    People should avoid insect bites, especially on their legs, and should use a repellent when exposed to insects.   Patients with deep vein thrombosis should be given the following additional lifestyle advice: regular walking exercise helps to reduce the risk of further deep vein thrombosis and improves circulation in the affected limb the affected leg should be elevated when sitting “If you are traveling for any length of time will need to move your dosing time gradually  – say by an hour a day – to a time that is convenient to the new zone. You may also need to have an INR check while you are away.”

    Yellow booklets and alert card

    1. Provide the patient with information about the INR monitoring booklet and patient information booklet
    2. Explain the importance of carrying the anticoagulant alert card with them at all

    At the start of treatment, all patients should be provided with two yellow anticoagulant booklets, an INR monitoring booklet, and a patient information booklet. Patients should also be provided with an anticoagulant alert card.

    Patients should be advised to always carry the anticoagulant alert card with them in case of an emergency and always take the yellow INR monitoring book with them to each appointment at the anticoagulant clinic and if possible to other appointments (e.g. GP, pharmacy reviews, dental appointments, etc).

    The patient information book is a useful resource since it provides the patient with a point of reference and reinforces what has been covered in this guide.

    Closing the consultation

    1. Summarise the key points back to the patient
    2. Ask the patient if they have any questions or concerns that have not been addressed
    3. Arrange appropriate follow-up
    4. Thank the patient for their time
    5. Dispose of PPE appropriately and wash your hands

    Key communication skills

    Summarise the key points back to the patient.

    Ask the patient if they have any questions or concerns that have not been addressed.

    If you feel that the patient would benefit from a recap session, arrange a follow-up appointment (face-to-face or telephone) and also direct the patient to the yellow anticoagulant information booklet for further reading.

    Thank the patient for their time.

    Dispose of PPE appropriately and wash your hands.

    Supplements materials

    Vitamin K Content of Selected Foods

    * Note: This is NOT a list of foods to avoid. This list provides information on the vitamin K content of certain foods.

    FoodsLowModerateHigh
    VegetablesGreen beans    AsparagusBroccoli
     CarrotsAvocadoBrussels sprouts
     CauliflowerRed CabbageCabbage
     CeleryGreen peasCollard greens
     Corn Endive (raw)
     Cucumber (peel removed)Pickle (dill)Kale (raw leaf)
     EggplantLettuce (iceberg)Lettuce (bib, red leaf)
     Mushrooms Mustard greens (raw)
     Onions Parsley
     Green pepper Spinach
     Potato Turnip greens (raw)
     Pumpkin Watercress (raw)
     Sauerkraut (canned) Swiss chard
     Tomato  
    FruitsApple  
     Banana  
     Blueberries  
     Grapes  
     Orange  
    MeatsBeef  
     Chicken  
     Pork  
     Tuna  
       Turkey  
    Fats and OilsCorn oilMargarineMayonnaise
     Peanut oilOlive oilCanola oil
     Safflower oil Soybean oil
     Sesame oil  
     Sunflower oil  
    Dairy ProductsButter  
     Cheese (cheddar)  
     Eggs  
     Sour cream  
     Yogurt  
    BeveragesCoffee  
     Cola  
     Fruit juices  
     Milk  
     Tea (black) Tea (green)**
    • Clotcare Online Resource at www.clotcare.com. (Accessed April 20, 2005).

    ** There is some controversy as to whether brewing green tea alters the vitamin K content and/or whether green tea may alter the effect of warfarin by some other mechanism.

    Potential Interactions of Dietary Supplements with Warfarina

    Potential Increase in Risk of Bleeding  
    Acetyl-L-carnitineFish oilMate
    ArnicaFlaxseed, Flaxseed oilMelatonin
    Alcohol, acute useFo-tiMesoglycan
    Bishop’s weedForskolinMilk thistle
    Black teaForsythiaN-acetyl glucosamine
    BladderwrackGamma-linolenic acidNattokinase
    BoldoGarlicOolong tea
    Borage seed oilGingerPantethine
    BurdockGinkgoPapaya
    CaffeineGinseng, SiberianPeppermint oil
    Chondroitin sulfateGlucosaminePropionyl-L-carnitine
    Cod liver oilGrapefruit, Grapefruit juiceRed clover
    ColtsfootGuaranaReishi mushroom
    Cranberry, cranberry juiceGuggulResveratrol
    DanshenHoly basilSaw palmetto
    Devil’s clawHoneysuckleSea buckthorn
    Dong quaiHorse chestnutTiratricol
    EpimediumIpriflavoneTurmeric
    Eucalyptus oilJiaogulanVinpocetine
    Evening primrose oilKavaVitamin A
    FenugreekL-carnitineVitamin E
    FeverfewLyciumWillow bark
      Wintergreen
    Possible Decrease in Warfarin’s Effects  
    Acerola  
    Alcohol, chronic use  
    Alfalfa  
    Cherokee rosehip  
    Chlorella  
    Coenzyme Q10  
    Corn silk  
    EDTA  
    Ginseng, American  
    Ginseng, Panax  
    Green tea  
    Limonene  
    Rose hip  
    Smartweed  
    Soy  
    Spinach  
    St. John’s wort  
    Stinging nettle  
    Vitamin C  
    Vitamin K  
    Watercress  

    aAdapted from Natural Medicines Comprehensive Database at www.naturaldatabase.com. (Accessed 4/21/05).

    Vitamin K and other Potential Interactions with warfarinDownload
    Loading...

    • Opening the consultation

    • Ideas, concerns and expectations

    • How warfarin works

    • INR

    • How to take warfarin

    • Bleeding whilst taking warfarin

    • Other side effects of warfarin

    • Lifestyle advice

    • Yellow booklets and alert card

    • Closing the consultation

    • Key communication skills

    Total: 0 / 37
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    Dialogue Simulator – Communication with a patient starting warfarin:


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    References:

    1. What You Should Know About Your Diet and Warfarin. PHARMACIST’S LETTER / Prescriber’s Letter to give to their patients. P.O. Box 8190, Stockton, CA 95208. May 2005 ~ Volume 21 ~ Number 210507, 8 p.
    2. Beatty SJ, Mehta BH, Rodis JL. Decreased warfarin effect after initiation of high-protein, lowcarbohydrate diets. Ann Pharmacother 2005;39:744
    3. Committee on Safety of Medicines (CSM). Current Problems in Pharmacovigilance 2003;29:8.
    4. Shields KM. Possible Cranberry and Warfarin Interaction. Pharmacist’s Letter/Prescriber’s Letter 2003;19(11):191103.
    5. Havrda DE, Mai T, Chonlahan J. Enhanced antithrombotic effect of warfarin associated with low-dose alcohol consumption. Pharmacotherapy 2005;25:303-7.
    6. OXFORD HAEMOPHILIA AND THROMBOSIS CENTRE PROTOCOLS FOR OUTPATIENT ORAL ANTICOAGULATION WITH VITAMIN K ANTAGONISTS. Prepared by D. Keeling with input and review from S. Shapiro, N. Curry, V. Price, and L. Mulholland.AC Protocols version 4.1 May 2017
    7. Paulus Kirchhof, Stefano Benussi, Dipak Kotecha, Anders Ahlsson, Dan Atar, Barbara Casadei, Manuel Castella, Hans-Christoph Diener, Hein Heidbuchel, Jeroen Hendriks, Gerhard Hindricks, Antonis S. Manolis, Jonas Oldgren, Bogdan Alexandru Popescu, Ulrich Schotten, Bart Van Putte, Panagiotis Vardas, Stefan Agewall, John Camm, Gonzalo Baron Esquivias, Werner Budts, Scipione Carerj, Filip Casselman, Antonio Coca, Raffaele De Caterina, Spiridon Deftereos, Dobromir Dobrev, José M. Ferro, Gerasimos Filippatos, Donna Fitzsimons, Bulent Gorenek, Maxine Guenoun, Stefan H. Hohnloser, Philippe Kolh, Gregory Y. H. Lip, Athanasios Manolis, John McMurray, Piotr Ponikowski, Raphael Rosenhek, Frank Ruschitzka, Irina Savelieva, Sanjay Sharma, Piotr Suwalski, Juan Luis Tamargo, Clare J. Taylor, Isabelle C. Van Gelder, Adriaan A. Voors, Stephan Windecker, Jose Luis Zamorano, Katja Zeppenfeld, 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS, EP Europace, Volume 18, Issue 11, November 2016, Pages 1609–1678, https://doi.org/10.1093/europace/euw295

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    Сообщение Counseling a patient who is taking warfarin / OSCE guide появились сначала на ClinCaseQuest.

    ]]>         King’s College Criteria for Non- Acetaminophen Toxicity acute hepatic failure https://clincasequest.hospital/kings-college-criteria-non-acetaminophen/ Tue, 04 Jan 2022 10:07:00 +0000 https://clincasequest.hospital/?p=31835 Identification of patients who should be immediately referred for liver transplant. INR > 6.5 (Prothrombin time > 100 sec): Yes No Patient age <11 or…

    Сообщение King’s College Criteria for Non- Acetaminophen Toxicity acute hepatic failure появились сначала на ClinCaseQuest.

    ]]>     Identification of patients who should be immediately referred for liver transplant.

    INR > 6.5 (Prothrombin time > 100 sec):
    Yes
    No

    Patient age <11 or > 40 years:
    Yes
    No

    Serum bilirubin level > 300 μmol/l:
    Yes
    No

    More than seven days passed from the onset of jaundice to the development of encelopathy:
    Yes
    No

    INR (international normalized ratio) >3.5 (prothrombin time > 50 seconds):
    Yes
    No

    Etiology – the absence of hepatitis A and B or the presence of an idiosyncratic reaction to a drug:
    Yes
    No

    Lactate >3.5 mmol/L after fluid
    resuscitation (<4 hrs) OR lactate > 3
    mmol/L after full fluid resuscitation (12 hours):
    Yes
    No

    Phosphate > 3.75 mg/dL (1.2 mmol/L) at 48-
    96 hours
    Yes
    No




    Patient’s score Result Comment
    0 0 0

    Patients with acute liver failure should be treated in centers that specialize in the care of such patients. The King’s College criteria can help identify patients who require liver transplantation.

    Criteria for non-acetaminophen-induced acute liver failure include:

    • 1 big criterion – International normalized ratio (INR)> 6.5; and
    • 5 small criteria:
      1. the patient’s age is <11 or> 40 years;
      2. the level of bilirubin in serum is more than 300 μmol per liter;
      3. More than seven days have passed from the onset of jaundice to the development of encelopathy;
      4. INR (international normalized ratio)> 3.5 (prothrombin time> 50 seconds);
      5. etiology – the absence of hepatitis A and B or the presence of an idiosyncratic reaction to a drug.

    Interpretation of results:

    A patient’s survival prognosis is poor if he has at least 1 major criterion or any 3 minor criteria.

    The King’s College criteria are recommended by the American Association for the Study of Liver Diseases (AASLD) for determining the need for liver transplantation in patients with acute liver failure.

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    References

    1. O’Grady JG, Alexander GJ, Hayllar KM, Williams R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology. 1989 Aug;97(2):439-45. doi: 10.1016/0016-5085(89)90081-4. PMID: 2490426. https://pubmed.ncbi.nlm.nih.gov/2490426/
    2. Bernal W, Donaldson N, Wyncoll D, Wendon J. Blood lactate as an early predictor of outcome in paracetamol-induced acute liver failure: a cohort study. Lancet. 2002 Feb 16;359(9306):558-63. doi: 10.1016/S0140-6736(02)07743-7. PMID: 11867109. https://pubmed.ncbi.nlm.nih.gov/11867109/
    3. Bailey B, Amre DK, Gaudreault P. Fulminant hepatic failure secondary to acetaminophen poisoning: a systematic review and meta-analysis of prognostic criteria determining the need for liver transplantation. Crit Care Med. 2003 Jan;31(1):299-305. doi: 10.1097/00003246-200301000-00048. PMID: 12545033. https://pubmed.ncbi.nlm.nih.gov/12545033/
    4. Schmidt LE, Dalhoff K. Serum phosphate is an early predictor of outcome in severe acetaminophen-induced hepatotoxicity. Hepatology. 2002; 36(3):659–665. doi: 10.1053/jhep.2002.35069. https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1053/jhep.2002.35069
    5. Riordan SM, Williams R. Treatment of hepatic encephalopathy. N Engl J Med. 1997 Aug 14;337(7):473-9. doi: 10.1056/NEJM199708143370707. PMID: 9250851. https://pubmed.ncbi.nlm.nih.gov/9250851/

    Charlson Comorbidity Index (CCI) Online Calculator

    Charlson Comorbidity Index predicts 10-year survival in patients with multiple comorbidities.

    History of definite or probable MI (EKG changes and/or enzyme changes)

    Exertional or paroxysmal nocturnal dyspnea and has responded to digitalis, diuretics, or afterload reducing agents

    Intermittent claudication or past bypass for chronic arterial insufficiency, history of gangrene or acute arterial insufficiency, or untreated thoracic or abdominal aneurysm (≥6 cm)

    History of a cerebrovascular accident with minor or no residua and transient ischemic attacks

    Chronic cognitive deficit

    Any history of treatment for ulcer disease or history of ulcer bleeding

    Severe = cirrhosis and portal hypertension with variceal bleeding history, moderate = cirrhosis and portal hypertension but no variceal bleeding history, mild = chronic hepatitis (or cirrhosis without portal hypertension)

    Severe = on dialysis, status post kidney transplant, uremia, moderate = creatinine >3 mg/dL (0.27 mmol/L)

    VariablePointsAge <50…
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    ≥1 of the following (A or B)

    ≥1 myeloma defining event (C1 or C2)

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    Сообщение King’s College Criteria for Non- Acetaminophen Toxicity acute hepatic failure появились сначала на ClinCaseQuest.

    ]]>         The Statin-Associated Muscle Symptom Clinical Index (SAMS-CI) https://clincasequest.hospital/sams-ci-calculator/ Mon, 27 Dec 2021 00:59:00 +0000 https://clincasequest.hospital/?p=31630 Regional distribution or pattern: Symmetric hip flexors or thigh aches Symmetric calf aches Symmetric upper proximal aches Nonspecific asymmetric, intermittent Temporal pattern: Symptoms onset <…

    Сообщение The Statin-Associated Muscle Symptom Clinical Index (SAMS-CI) появились сначала на ClinCaseQuest.

    ]]>     Regional distribution or pattern:
    Symmetric hip flexors or thigh aches
    Symmetric calf aches
    Symmetric upper proximal aches
    Nonspecific asymmetric, intermittent

    Temporal pattern:
    Symptoms onset < 4 weeks
    Symptoms onset 4-12 weeks
    Symptoms onset >12 weeks

    Dechallenge:
    Improves upon withdrawal (< 2 weeks)
    Improves upon withdrawal (2-4 weeks)
    Does not improve upon withdrawal (> 4 weeks)

    Challenge:
    Same symptoms reoccur upon rechallenge < 4 weeks
    Same symptoms reoccur upon rechallenge 4-12 weeks




    Score Range of points Statin myalgia clinical index score
    0 0 0

    Determination of the clinical index of statin-associated muscle symptoms

    Clinical symptoms (new or increased unexplained muscle symptoms)Points
    Regional distribution/pattern 
    Symmetric hip flexors/thigh aches3
    Symmetric calf aches2
    Symmetric upper proximal aches2
    Nonspecific asymmetric, intermittent1
    Temporal pattern 
    Symptoms onset <4 weeks3
    Symptoms onset 4-12 weeks2
    Symptoms onset >12 weeks1
    Dechallenge 
    Improves upon withdrawal (<2 weeks)2
    Improves upon withdrawal (2-4 weeks)1
    Does not improve upon withdrawal (>4 weeks)0
    Challenge 
    Same symptoms reoccur upon rechallenge <4 weeks3
    Same symptoms reoccur upon rechallenge 4-12 weeks1
     
    Statin myalgia clinical index score  
    Probable9-11
    Possible7-8
    Unlikely<7

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    Source:
    The Statin-Associated Muscle Symptom Clinical Index (SAMS-CI): Revision for Clinical Use, Content Validation, and Inter-rater Reliability.Rosenson RS, Miller K, Bayliss M, Sanchez RJ, Baccara-Dinet MT, Chibedi-De-Roche D, Taylor B, Khan I, Manvelian G, White M, Jacobson TA.Cardiovasc Drugs Ther. 2017 Apr;31(2):179-186. doi: 10.1007/s10557-017-6723-4.PMID: 28421332

    Charlson Comorbidity Index (CCI) Online Calculator

    Charlson Comorbidity Index predicts 10-year survival in patients with multiple comorbidities.

    History of definite or probable MI (EKG changes and/or enzyme changes)

    Exertional or paroxysmal nocturnal dyspnea and has responded to digitalis, diuretics, or afterload reducing agents

    Intermittent claudication or past bypass for chronic arterial insufficiency, history of gangrene or acute arterial insufficiency, or untreated thoracic or abdominal aneurysm (≥6 cm)

    History of a cerebrovascular accident with minor or no residua and transient ischemic attacks

    Chronic cognitive deficit

    Any history of treatment for ulcer disease or history of ulcer bleeding

    Severe = cirrhosis and portal hypertension with variceal bleeding history, moderate = cirrhosis and portal hypertension but no variceal bleeding history, mild = chronic hepatitis (or cirrhosis without portal hypertension)

    Severe = on dialysis, status post kidney transplant, uremia, moderate = creatinine >3 mg/dL (0.27 mmol/L)

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    ≥1 of the following (A or B)

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    Сообщение The Statin-Associated Muscle Symptom Clinical Index (SAMS-CI) появились сначала на ClinCaseQuest.

    ]]>