Why is warfarin prothrombotic initially

Therapy of acute thromboembolism with heparin and warfarin. Clin Pharm. Am J Health Syst Pharm. Wittkowsky AK. Generic warfarin: implications for patient care [Editorial]. Medical and economic consequences of a blinded oral anticoagulant brand change at a municipal hospital. Pharmacokinetics and pharmacodynamics of warfarin at steady state.

Br J Clin Pharmacol. Hemorrhagic complications of anticoagulant treatment. Anticoagulant-related bleeding: clinical epidemiology, prediction, and prevention.

Am J Med. Major bleeding in outpatients treated with warfarin: incidence and prediction by factors known at the start of outpatient therapy. Albers GW. Atrial fibrillation and stroke: three new studies, three remaining questions. Risk factors for stroke and efficacy of anti-thrombotic therapy in atrial fibrillation: analysis of pooled data from five randomized controlled trials.

Risk factors for complications of chronic anticoagulation: a multicenter study. Bleeding complications to oral anticoagulant therapy: multivariate analysis of treatment years in outpatients.

J Intern Med. The risk for and severity of bleeding complications in elderly patients treated with warfarin. Stroke prevention in atrial fibrillation study: final results.

An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation. Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial.

Richard W. Sloan, M. Hospital and clinical associate professor in family and community medicine at the Milton S. This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP.

Contact afpserv aafp. Want to use this article elsewhere? Get Permissions. Read the Issue. Sign Up Now. Previous: Exfoliative Dermatitis. Next: Vaginal Bleeding at 16 Weeks.

Feb 1, Issue. Warfarin Therapy: Evolving Strategies in Anticoagulation. Warfarin is the oral anticoagulant most frequently used to control and prevent thromboembolic disorders. TABLE 2 Risk Factors for Hemorrhagic Complications of Anticoagulation Therapy Age greater than 65 years 23 Age greater than 75 years with concomitant atrial fibrillation intracranial hemorrhage 24 , 25 History of gastrointestinal bleeding 20 Comorbid disease states 26 Hypertension 20 , 27 Cerebrovascular disease 20 Serious heart disease 4 , 20 Renal insufficiency 20 Information from references 4 , 20 , and 23 through Amiodarone Cordarone Moderate Delayed Excellent Decreases warfarin metabolism within a week of coadministration; effect may persist for 1 to 3 months after discontinuation of amiodarone May induce hypothyroidism or hyperthyroidism A 25 percent reduction in the warfarin dosage is recommended when amiodarone is initiated.

Antithyroid drugs Moderate Delayed Fair Hyperthyroidism results in metabolism of vitamin K clotting factors and increased sensitivity to oral anticoagulants Monitor INR when antithyroid medications are added or withdrawn. Barbiturates Major Delayed Excellent Increase warfarin metabolism and frequently reduce hypoprothrombinemic effect of warfarin Monitor INR when barbiturates are added or withdrawn; the addition of warfarin in patients stabilized on a chronic barbiturate regimen is of less significance.

Binding resins Moderate Delayed Good Decrease absorption and may interrupt enterohepatic recirculation of warfarin Use colestipol Colestid , which has a lower potential for interaction, instead of cholestyramine Questran in patients who need a bile sequestrant. Cephalosporins Moderate Delayed Poor Methylthiotetrazole ring in cefoperazone Cefobid , cefamandole Mandol , cefotetan Cefotan and cefmetazole Zefazone inhibits production of vitamin K—dependent clotting factors Avoid concomitant use of warfarin and cefoperazone, cefamandole, cefotetan or cefmetazole.

Cimetidine Tagamet Moderate Delayed Excellent Inhibits warfarin metabolism; predominantly affects R isomer Use alternative agents in patients receiving warfarin.

Monitor INR when concomitant use of warfarin and cimetidine is necessary. Contraceptives, oral Minor Delayed Poor May increase clotting factor synthesis May inhibit oxidative metabolism If possible, avoid oral contraceptives because of increased risk of thromboembolism Monitor INR frequently when oral contraceptives are used concurrently with warfarin.

Diflunisal Dolobid Moderate Delayed Fair Displaces warfarin from protein binding, inhibits platelet aggregation, causes gastric erosions If possible, avoid concomitant use of warfarin and diflunisal. Disulfiram Antabuse Moderate Delayed Fair Inhibits warfarin metabolism If possible, avoid concomitant use of warfarin and disulfiram. Ethanol Moderate Delayed Excellent Acute ethanol use may inhibit anticoagulant metabolism.

Be aware of small risk of bleeding events. Metronidazole Flagyl Moderate Delayed Fair Inhibits metabolism of S enantiomer of warfarin Avoid concomitant use of warfarin and metronidazole. Nalidixic acid NegGram Moderate Delayed Poor Displaces warfarin from protein-binding sites Inhibits warfarin metabolism Avoid concomitant administration of warfarin and nalidixic acid. Penicillin may reduce gastrointestinal flora synthesis of vitamin K. Displaces warfarin from protein-binding sites Enhances metabolism of clotting factors Propafenone Rythmol Moderate Delayed Fair Probably inhibits warfarin metabolism Monitor INR frequently when propafenone is added or discontinued.

Increase warfarin metabolism Salicylates Major Delayed Excellent Inhibit platelet aggregation Cause gastric erosions In large doses, result in hypoprothrombinemic effect If possible, avoid concurrent use of warfarin and salicylates.

Sulfinpyrazone Anturane Moderate Delayed Excellent Inhibits warfarin metabolism If possible, avoid concomitant use of warfarin and sulfinpyrazone. Monitor for bleeding when concomitant use is necessary. Inhibits platelet aggregation Trimethoprim-sulfamethoxazole Bactrim Major Delayed Excellent Sulfonamide component may stereoselectively inhibit S isomer metabolism.

Monitor INR when concomitant use is necessary. Vitamin E Moderate Delayed Fair May interfere with production of clotting factors Interaction is probably dose-related and more likely to occur with vitamin E dosages greater than U per day; monitor INR if larger dosages are taken. Vitamin K Moderate Delayed Excellent Effects of oral anticoagulants are directly antagonized by the excessive ingestion of foods or dietary supplements containing vitamin K.

Read the full article. Get immediate access, anytime, anywhere. Choose a single article, issue, or full-access subscription. Earn up to 6 CME credits per issue. Purchase Access: See My Options close. Best Value!

To see the full article, log in or purchase access. More in Pubmed Citation Related Articles. Email Alerts Don't miss a single issue. Sign up for the free AFP email table of contents. Navigate this Article. Prophylaxis of venous thrombosis for high-risk surgery. Treatment of venous thrombosis. Treatment of pulmonary embolism. Prevention of systemic embolism. Chronic or intermittent. Prosthetic heart valves.

Clinical judgment 3 months optional. Acetaminophen Tylenol. Inhibits warfarin metabolism. Allopurinol Zyloprim. Monitor INR when allopurinol is added or withdrawn. Amiodarone Cordarone. Monitor INR when azole antifungals are added or withdrawn. Monitor INR when antithyroid medications are added or withdrawn. Decrease absorption and may interrupt enterohepatic recirculation of warfarin.

Carbamazepine Tegretol. Increases warfarin metabolism. Monitor INR intensively when carbamazepine is added or discontinued. Inhibits warfarin metabolism; predominantly affects R isomer. Use alternative agents in patients receiving warfarin. Produce hypercoagulability. Monitor for gastric toxicity. May have ulcerogenic effects. May increase endogenous anticoagulants. Monitor prothrombin time and INR for 2 days to 3 weeks after danazol is added.

If possible, avoid concomitant use of warfarin and diflunisal. Disulfiram Antabuse. If possible, avoid concomitant use of warfarin and disulfiram. Probably inhibits warfarin metabolism. Monitor INR more closely for 1 to 2 weeks after fluvoxamine is started.

Has additive anticoagulant effects. Heparin may prolong INR, and warfarin may prolong partial thrombin time. HMG CoA reductase inhibitors. May inhibit warfarin metabolism. Monitor INR when isoniazid is added or withdrawn. Metronidazole Flagyl. Inhibits metabolism of S enantiomer of warfarin. Avoid concomitant use of warfarin and metronidazole. Nalidixic acid NegGram. Monitor INR frequently when paroxetine is added.

Induces warfarin metabolism. Monitor INR frequently for 1 month or more after phenytoin is added. Displaces warfarin from protein-binding sites. Enhances metabolism of clotting factors. Propafenone Rythmol. Monitor INR frequently when propafenone is added or discontinued. Possibly inhibit warfarin metabolism. Rifampin Rifadin and rifabutin Mycobutin. The information below may be incorrect and so hence, as per our disclaimer, do use your own clinical judgement.

Scenario 1: Newly starting or restarting anticoagulation The decision to start or restart anticoagulation should be senior-led. To select the right agent, consider factors impacting the patient and their relative as well as counselling them on risks and benefits. Do take into account the risk of bleeding e.

Patients newly starting on anticoagulation are usually seen in the anticoagulation clinic. For surgical patients or those requiring procedures:. Scenario 2: Transitioning between anticoagulation Have a low threshold to discuss with seniors and haematology if the patient has a high risk of bleeding or thrombosis. Here we talk only about patients with a target of INR 2. This is due to the following factors. Generally, the accepted dose range is 0.

What to do if the INR is too high? Average rating 3. Vote count: 9. No votes so far! One of the products of such trials is the knowledge that when starting Warfarin, some patients will need higher doses than others.

However, this practice is still being studied and currently, Warfrain should be given empirically and not on an genetically-individualized basis. Warfarin has a narrow therapeutic range.

This means that given in too low a dose it may cause thrombosis while give too much bleeding may occur. Register New Account Log in to renew or change an existing membership.

Register to enjoy all our content including Vascular Medicine Board Review tests. What describes you best? Email Format html text. Vascular Medicine About. Starting Warfarin. Published by Dr. Ido Weinberg at March 8, Last modified on June 27th, Ido Weinberg Dr. Weinberg is Founder and Editor in Chief of the Angiologist. View All Articles by Dr. What is the first dose when starting warfarin?

When starting warfarin is heparin overlap necessary? How should the daily dose of Warfarin be calculated? Should starting Warfarin be done according to a genetic profile? Complications of Warfarin treatment Warfarin has a narrow therapeutic range. Large hematoma necessitating transfusion. Related posts.