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anticoagulation

Indications: 1) treatment of deep vein thrombosis, pulmonary embolus, atrial fibrillation or valvular heart disease: INR 2.0-3.0; atrial fibrillation with rheumatic valve disease: INR 2.5-3.5 2) antiphospholipid antibody syndrome: INR 3.0-4.0 3) mechanical prosthetic heart valves:* INR 2.5-3.5 4) arterial thrombosis or prevention of recurrent myocardial infarction: INR 2.5-3.5 5) treatment of arterial thromboembolism, 1st generation mechanical heart valves (Star-Edwards or Bjork-Shiley): INR 2.5-3.5 + aspirin 80-100 mg QD 6) recurrent systemic embolism: INR 3.0-4.5 7) long-term low-intensity anticoagulation for patients with idiopathic deep vein thrombosis: INR 1.5-2.0 (after 3 months of standard therapy) [3] not recommended * except 1st generation mechanical heart valves (Star-Edwards or Bjork-Shiley); may be combined with aspirin for high- risk patients at the cost of increased risk of bleeding Contraindications: - high risk of falls may not be an absolute contraindication [11] - warfarin may cause more harm than benefit in patients with atrial fibrillation & end-stage renal disease (ESRD)* * apixaban may be used in ESRD with close monitoring [1] Benefit/risk: - treatment of deep vein thrombosis & pulmonary embolism - no benefit in mortality or prevention of pulmonary embolism [20] - number needed to harm: 50-111 to cause 1 major hemorrhage - widely accepted in clinical practice, thus preventing initiating of randomized clinical trials due to ethical concerns [20] Monitor: 1) after stabilization of dose, INR is monitored monthly for most patients (every other month for low-intensity anticoagulation) 2) self management may be appropriate for subgroup [7] Complications: (also see warfarin) - intracranial hemorrhage - risk associated with INR > 3.5, age > 85 [5] - reversal of INR to < 1.3 within 4 hours & systolic BP to < 160 mm Hg at 4 hours is associated with lower rate of intracranial hematoma enlargement [21] - bleeding, especially GI bleeding - 6 fold increased risk of intracerebral hemorrhage - risk of major hemorrhage 13.1 events/100 patient years in elderly >= 80 vs 4.75 in patients < 80 [8] - scoring systems no better than physician clinical judgment in predicting major hemorrhage [12] - risk of bleeding increased in patients with advanced renal failure [27] - risks of bleeding & thrombosis lower with apixaban than warfarin in patients with ESRD [27] - when to restart anticoagulation after GI blood is controversial - after resolution of GI bleed [1] - especially in patients with malignancy [19] - within 7 days to reduce risk of thromboembolic event [1] - predicted rates of major bleeding from clinical trials underestimate rates actually observed with warfarin or dabigatran [22] - heavy menstrual bleeding (menorrhagia) [23] - 22-65% with warfarin - 32% with rivaroxaban - 28% with apixaban - 25% with edoxaban - concurrent use of antiplatelet agents (including SSRI) further increases risk of bleeding - resumption of oral anticoagulant therapy is associated with a lower risk of ischemic events [21] Management: 1) anticoagulation for non-cardiac surgery - see perioperative anticoagulation 2) contraception for women on warfarin anticoagulation a) do not use estrogen-containing contraceptives - increased risk of thromboembolism b) progestin-only contraceptives appear safe c) intrauterine device (IUD) - levonorgestrel-releasing intrauterine device (LNG-IUD) is effective for heavy menstrual bleeding associated with anticoagulation or bleeding disorders 3) pregnancy a) switch to unfractionated heparin or LMW heparin after week 6; switch to unfractionated heparin at week 37 to term b) exception: mechanical heart valve - follow procedure under mechanical heart valve c) in some cases, continued use of warfarin may be justified [1] d) week 37 to term, switch to unfractionated heparin to allow abrupt discontinuation of anticoagulation during labor & delivery [1] e) continuation of LMW heparin to term discontinuing 24 hours prior to delivery [29] 4) lactation - warfarin considered safe; does not appear in breast milk - LMW heparin considered safe; does not appear in breast milk - unknown whether direct oral anticoagulants appear in breast milk - fondaparinux excreted in breast milk of lactating rats [1] 5) anticoagulation in patients with active malignancy - LMW heparin anticoagulant of choice [29] - thromboprophylaxis with direct oral anticoagulants in ambulatory patients with cancer is safe & effective [25] - direct oral anticoagulants are non-inferior to LMW heparin in preventing venous thromboembolism in patients with cancer over 6 months [30] - compared with LMW heparin & warfarin, direct oral anticoagulants are associated with better medication compliance, lower incidence of venous thromboembolism, lower risk of bleeding & lower mortality [31] 6) end-stage renal disease, renal dialysis - warfarin - treatment of choice in patients with chronic renal failure stage 5 (NEJM) [29] - apixaban may be used with close monitoring [1] - also see atrial fibrillation (Management:) anticoagulation in renal failure 7) inferior vena cava filter for prevention of pulmonary embolism in patients with contraindication(s) to anticoagulation [1] 8) newer anticoagulants (direct oral anticoagulants) - see direct oral anticoagulant (DOAC) for safety vs warfarin - excluding mechanical heart valves, hypertrophic cardiomyopathy [1] - DOAC ok for atrial fibrillation in patients with bioprosthetic values [32] - dabigatran, rivaroxaban, & apixaban are safe & effective in the elderly [18] - direct oral anticoagulants are safer than wafarin in the very old [28] 9) dosage-adusted warfarin - mechanical heart valves, hypertrophic cardiomyopathy [1] 10) adding aspirin to warfarin associated with increased risk of bleeding without a benefit for thrombosis prevention [26] 11) tranexamic acid in oral doses every 6-8 hours or a single 10-mg/kg intravenous dose to control acute hemorrhaging [23] 12) in patients for whom heparin is initiated for anticoagulation, & titration to therapeutic effect is difficult, consider antithrombin deficiency * risk factors for perioperative thrombosis [1] - DVT within 1 year or history of recurrent DVT - atrial fibrillation with CHADS score > 2 - if CHADS score >= 4, especially in the setting of prior thromboembolic event or intracardiac thrombus, perioperative bridging with enoxaparin is appropriate [17] - prior stroke - active malignancy (treated within 6 months or palliatively) - hypercoagulable state - mechanical heart valve * high-risk patients undergoing cardiac device surgery have fewer complications continuing warfarin than switching to heparin [13]

Related

coagulation cascade coagulation factor direct oral anticoagulant; novel oral anticoagulant (DOAC, NOAC) heparin International normalized ratio (INR) prophylaxis for venous thromboembolism (VTE) warfarin (Coumadin, Panwarfin, Jantoven)

Specific

perioperative anticoagulation perioperative antiplatelet therapy

General

pharmacologic therapy

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2022
  2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 350
  3. Prescriber's Letter 10(3):13 2003
  4. 6th ACCP Consensus Conference on Antithrombic Therapy, American College of Physicians; Chest 119/1 Suppl Jan 2001
  5. Journal Watch 25(2):14, 2005 Fang MC, Chang Y, Hylek EM, Rosand J, Greenberg SM, Go AS, Singer DE. Advanced age, anticoagulation intensity, and risk for intracranial hemorrhage among patients taking warfarin for atrial fibrillation. Ann Intern Med. 2004 Nov 16;141(10):745-52. Summary for patients in: Ann Intern Med. 2004 Nov 16;141 (10):I38. PMID: 15545674
  6. Fang MC, Singer DE. Anticoagulation for atrial fibrillation. Cardiol Clin. 2004 Feb;22(1):47-62. Review. PMID: 14994847
  7. Fitzmaurice DA, Self management of oral anticoagulation: Randomized trial. BMJ 2005; 331:1057 PMID: 16216821 - Heneghan C, Alonso-Coello P, Garcia-Alamino JM, Perera R, Meats E, Glasziou P. Self-monitoring of oral anticoagulation: a systematic review and meta-analysis. Lancet. 2006 Feb 4;367(9508):404-11. Review. PMID: 16458764
  8. Hylek EM et al, Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007, 115:2689 PMID: 17515465 - Wyse DG Bleeding while starting anticoagulation for thromboembolism prophylaxis in elderly patients with atrial fibrillation: From bad to worse. Circulation 2007, 115:2684 PMID: 17533193
  9. Garcia DA et al, Risk of thromboembolism with short-term iterruption of warfarin therapy. Arch Intern Med 2008, 168:63 PMID: 18195197
  10. Culwell KR & Curtis KM. Use of contraceptive methods by women with current venous thrombosis on anticoagulant therapy: A systematic review. Contraception 2009 Oct; 80:337. PMID: 19751856
  11. Donze J et al. Risk of falls and major bleeds in patients on oral anticoagulation therapy. Am J Med 2012 Aug; 125:773 PMID: 22840664
  12. Donze J et al. Scores to predict major bleeding risk during oral anticoagulation therapy: A prospective validation study. Am J Med 2012 Nov; 125:1095. PMID: 22939362
  13. Birnie DH et al Pacemaker or Defibrillator Surgery without Interruption of Anticoagulation. N Engl J Med. May 8, 2013 PMID: 23659733 http://www.nejm.org/doi/full/10.1056/NEJMoa1302946
  14. Armstrong MJ et al Summary of evidence-based guideline: Periprocedural management of antithrombotic medications in patients with ischemic cerebrovascular disease. Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology May 28, 2013 vol. 80 no. 22 2065-2069 PMID: 23713086 http://www.neurology.org/content/80/22/2065.full
  15. Douketis JD, Berger PB, Dunn AS et al The perioperative management of antithrombotic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):299S-339S. PMID: 18574269 - Douketis JD, Spyropoulos AC, Spencer FA et al Perioperative management of antithrombotic therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence- Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e326S-50S. PMID: 22315266 (corresponding NGC guideline withdrawn Dec 2017)
  16. Shah M et al. Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis. Circulation 2014 Mar 18; 129:1196. PMID: 24452752 http://circ.ahajournals.org/content/129/11/1196 - Granger CB and Chertow GM. A pint of sweat will save a gallon of blood: A call for randomized trials of anticoagulation in end-stage renal disease. Circulation 2014 Mar 18; 129:1190 PMID: 24452751 http://circ.ahajournals.org/content/129/11/1190
  17. Baron TH, Kamath PS, McBane RD. Management of antithrombotic therapy in patients undergoing invasive procedures. N Engl J Med. 2013; 368:2113-2124. PMID: 24024854
  18. Sardar P et al. New oral anticoagulants in elderly adults: Evidence from a meta-analysis of randomized trials. J Am Geriatr Soc 2014 May; 62:857 PMID: 24786913 http://onlinelibrary.wiley.com/doi/10.1111/jgs.12799/abstract
  19. Sengupta N et al. The risks of thromboembolism vs. recurrent gastrointestinal bleeding after interruption of systemic anticoagulation in hospitalized inpatients with gastrointestinal bleeding: A prospective study. Am J Gastroenterol 2014 Dec 16 PMID: 25512338 http://www.nature.com/ajg/journal/vaop/ncurrent/full/ajg2014398a.html
  20. The NNT: Anticoagulation Given for Acute Venous Thromboembolism (Deep Venous Thrombosis and Pulmonary Embolism). http://www.thennt.com/nnt/anticoagulation-for-venous-thromboembolism/ - Cundiff DK et al. Anticoagulants vs non-steroidal anti-inflammatories or placebo for treatment of venous thromboembolism. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD003746. PMID: 1643746
  21. Kuramatsu JB et al. Anticoagulant reversal, blood pressure levels, and anticoagulant resumption in patients with anticoagulation- related intracerebral hemorrhage. JAMA 2015 Feb 24; 313:824 PMID: 25710659
  22. Wang SV, Franklin JM, Glynn RJ et al. Prediction of rates of thromboembolic and major bleeding outcomes with dabigatran or warfarin among patients with atrial fibrillation: New initiator cohort study. BMJ 2016 May 24; 353:i2607 PMID: 27221664 Free PMC Article http://www.bmj.com/content/353/bmj.i2607
  23. Boonyawat K, O'Brien SH, Bates SM. How we treat heavy menstrual bleeding associated with anticoagulants. Blood 2017 Nov 1; PMID: 29092828
  24. Writing Committee, Tomaselli GF, Mahaffey KW, Cuker A et al 2017 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants. A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol. 2017 Nov 10. pii: S0735-1097(17)40938-7 PMID: 29203195 http://www.onlinejacc.org/content/early/2017/11/10/j.jacc.2017.09.1085
  25. Agnelli G. Direct Oral Anticoagulants for Thromboprophylaxis in Ambulatory Patients with Cancer. N Engl J Med 2019; 380:781-783. Feb 21, 2019 PMID: 30786193 https://www.nejm.org/doi/full/10.1056/NEJMe1816060?query=TOC
  26. Schaefer JK, Li Y, Gu X et al Association of Adding Aspirin to Warfarin Therapy Without an Apparent Indication With Bleeding and Other Adverse Events. JAMA Intern Med. Published online March 4, 2019. PMID: 30830172 https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2726050
  27. Hanni C, Petrovitch E, Ali M et al. Outcomes associated with apixaban vs warfarin in patients with renal dysfunction. Blood Adv 2020 Jun 9; 4:2366 PMID: 32463871 Free PMC article https://ashpublications.org/bloodadvances/article/4/11/2366/457796/Outcomes-associated-with-apixaban-vs-warfarin-in
  28. Chao TF, Chiang CE, Chan YH et al Oral Anticoagulants in Extremely High Risk Very Elderly (>90 years) Patients with Atrial Fibrillation. Heart Rhythm. 2021, Feb 24 PMID: 33640447 https://www.heartrhythmjournal.com/article/S1547-5271(21)00180-6/fulltext
  29. NEJM Knowledge+ Hematology
  30. Schrag D, Uno H, Rosovsky R et al Direct Oral Anticoagulants vs Low-Molecular-Weight Heparin and Recurrent VTE in Patients With Cancer. A Randomized Clinical Trial. JAMA. 2023;329(22):1924-1933 PMID: 37266947 https://jamanetwork.com/journals/jama/fullarticle/2805894
  31. Riaz IB et al. Comparative effectiveness of anticoagulants in patients with cancer-associated thrombosis. JAMA Netw Open 2023 Jul 3; 6:e2325283. PMID: 37486628 PMCID: PMC10366701 Free PMC article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2807546
  32. Suppah M, Kamal A, Saadoun R, et al. An Evidence-Based Approach to Anticoagulation Therapy Comparing Direct Oral Anticoagulants and Vitamin K Antagonists in Patients With Atrial Fibrillation and Bioprosthetic Valves: A Systematic Review, Meta-Analysis, and Network Meta-Analysis. Am J Cardiol. 2023 Sep 11;206:132-150 PMID: 37703679