Hemodialysis for the treatment of dabigatran-associated bleeding: A case report and systematic review

Journal of Thrombosis and Haemostasis

Volumn 13, Issue 10, 2015, Pages 1790-1798

  Chai Adisaksopha, C ^a,b   Hillis, C ^b   Lim, W ^b   Boonyawat, K ^b   Moffat, K ^b   Crowther, M ^b,c  

^a CHIANG MAI UNIVERSITY   (Thailand)

^b MCMASTER UNIVERSITY   (Canada)

^c MCMASTER UNIVERSITY   (Canada)

Author keywords

Anticoagulants; Dabigatran; Hemorrhage; Renal dialysis; Thromboembolism

Indexed keywords

CREATININE; DABIGATRAN; DABIGATRAN ETEXILATE; FRESH FROZEN PLASMA; WARFARIN; ANTITHROMBIN; BIOLOGICAL MARKER;

AGED; ARTICLE; ATRIAL FIBRILLATION; BLEEDING; BRAIN HEMORRHAGE; CASE REPORT; COLON RESECTION; COMPUTER ASSISTED TOMOGRAPHY; CONTINUOUS HEMODIAFILTRATION; CONTINUOUS RENAL REPLACEMENT THERAPY; CONTROLLED STUDY; CREATININE BLOOD LEVEL; CREATININE CLEARANCE; DEATH; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG ELIMINATION; DRUG SUBSTITUTION; DRUG WITHDRAWAL; EPISTAXIS; ERYTHROCYTE TRANSFUSION; FLANK PAIN; GASTROINTESTINAL HEMORRHAGE; HEART VENTRICLE THROMBOSIS; HEMARTHROSIS; HEMODIALYSIS; HEMOSTASIS; HUMAN; HYPOTENSION; INTENSIVE CARE; INTERNATIONAL NORMALIZED RATIO; INTESTINE ISCHEMIA; LAPAROTOMY; LUNG HEMORRHAGE; MALE; PARTIAL THROMBOPLASTIN TIME; PRIORITY JOURNAL; RENAL REPLACEMENT THERAPY; RETROPERITONEAL HEMORRHAGE; SEPTIC SHOCK; SYSTEMATIC REVIEW; VENOUS THROMBOEMBOLISM; BLOOD; BLOOD CLOTTING; BLOOD CLOTTING TEST; CHEMICALLY INDUCED; DRUG EFFECTS; FEMALE; HEMORRHAGE; MIDDLE AGED; RISK FACTOR; TREATMENT OUTCOME; VERY ELDERLY;

AGED; AGED, 80 AND OVER; ANTITHROMBINS; BIOMARKERS; BLOOD COAGULATION; BLOOD COAGULATION TESTS; DABIGATRAN; FEMALE; HEMORRHAGE; HUMANS; MALE; MIDDLE AGED; RENAL DIALYSIS; RISK FACTORS; TREATMENT OUTCOME;

EID: 84942871422     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/jth.13117     Document Type: Article

References (43)

1. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-51.
2. Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, Prins MH, Hettiarachchi R, Hantel S, Schnee J, Buller HR; RE-NOVATE Study Group. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet. 2007; 370: 949-56.
3. Stangier J, Clemens A. Pharmacology, pharmacokinetics, and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor. Clin Appl Thromb Hemost 2009; 15(Suppl. 1): 9S-16S.
4. Stangier J, Rathgen K, Stahle H, Gansser D, Roth W. The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjects. Br J Clin Pharmacol 2007; 64: 292-303.
5. Blech S, Ebner T, Ludwig-Schwellinger E, Stangier J, Roth W. The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans. Drug Metab Dispos 2008; 36: 386-99.
6. Stangier J, Rathgen K, Stahle H, Mazur D. Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate: an open-label, parallel-group, single-centre study. Clin Pharmacokinet 2010; 49: 259-68.
7. Schulman S, Eriksson H, Goldhaber SZ, Kakkar A, Kearon C, Schellong SM, Feuring M, Peter N, Friedman J. Influence of renal function on the efficacy and safety of dabigatran versus warfarin for the treatment of acute venous thromboembolism: a pooled analysis from RE-Cover and RE-Cover II. Blood 2013; 122: 212. (abstract)
8. Wilson JA, Goralski KB, Soroka SD, Morrison M, Mossop P, Sleno L, Wang Y, Anderson DR. An evaluation of oral dabigatran etexilate pharmacokinetics and pharmacodynamics in hemodialysis. J Clin Pharmacol 2014; 54: 901-9.
9. Khadzhynov D, Wagner F, Formella S, Wiegert E, Moschetti V, Slowinski T, Neumayer HH, Liesenfeld KH, Lehr T, Hartter S, Friedman J, Peters H, Clemens A. Effective elimination of dabigatran by haemodialysis. A phase I single-centre study in patients with end-stage renal disease. Thromb Haemost 2013; 109: 596-605.
10. Warkentin TE, Margetts P, Connolly SJ, Lamy A, Ricci C, Eikelboom JW. Recombinant factor VIIa (rFVIIa) and hemodialysis to manage massive dabigatran-associated postcardiac surgery bleeding. Blood 2012; 119: 2172-4.
11. Lowe MP, Collins J, Yehia M, Eaddy N. Reversal of dabigatran with haemodialysis in a patient requiring decompression for cord compression from an epidural abscess. Nephrology 2013; 18: 580-2.
12. Higgin JPT, Deeks JJ. Selecting studies and collecting data. In: Higgins JPT, Green S, eds. Cochrane Handbook for Systematic Review of Interventions Version 5.1.0 [updated March 2011]. Chichester, UK: Wiley, 2008: 151-83.
13. Chang DN, Dager WE, Chin AI. Removal of dabigatran by hemodialysis. Am J Kidney Dis 2013; 61: 487-9.
14. Chen BC, Sheth NR, Dadzie KA, Smith SW, Nelson LS, Hoffman RS, Winchester JF. Hemodialysis for the treatment of pulmonary hemorrhage from dabigatran overdose. Am J Kidney Dis 2013; 62: 591-4.
15. Cronin J, Sivarajaratnam M. Poor efficacy of haemodiafiltration to treat dabigatran-associated coagulopathy. JICS 2014; 15: 154-7.
16. Esnault P, Gaillard PE, Cotte J, Cungi PJ, Beaume J, Prunet B. Haemodialysis before emergency surgery in a patient treated with dabigatran. Br J Anaesth 2013; 111: 776-7.
17. Harinstein LM, Morgan JW, Russo N. Treatment of dabigatran-associated bleeding: case report and review of the literature. J Pharm Pract 2013; 26: 264-9.
18. Kim J, Yadava M, An IC, Sayeed A, Laird-Fick HS, Gourineni V, Abela GS. Coagulopathy and extremely elevated PT/INR after dabigatran etexilate use in a patient with end-stage renal disease. Case Report Med 2013; 2013: 1-4.
19. Lal Y, van Heukelom J. Dabigatran: a cause of hematologic emergency. Am J Med Sci 2013; 346: 190-3.
20. Lillo-Le Louet A, Wolf M, Soufir L, Galbois A, Dumenil AS, Offenstadt G, Samama MM. Life-threatening bleeding in four patients with an unusual excessive response to dabigatran: implications for emergency surgery and resuscitation. Thromb Haemost 2012; 108: 583-5.
21. Pazmino PA. Dabigatran associated acute renal failure (DAARF). Am J Kidney Dis 2012; 59: A63. (abstract)
22. Robertson A, Bellamy C, Negoianu D, Candeloro C. Management of dabigatran-associated severe bleeding with continuous renal replacement therapy. Crit Care Med 2013; 41(Suppl. 1): A321-2 (abstract).
23. Silinskie K, Hite M. Reversal of dabigatran-induced gastrointestinal bleed in a patient with acute kidney injury. Crit Care Med 2013; 41(Suppl. 1): A299 (abstract).
24. Singh T, Maw TT, Henry BL, Pastor-Soler NM, Unruh ML, Hallows KR, Nolin TD. Extracorporeal therapy for dabigatran removal in the treatment of acute bleeding: a single center experience. Clin J Am Soc Nephrol 2013; 8: 1533-9.
25. Stein P, Bosshart M, Brand B, Schlicker A, Spahn DR, Bettex D. Dabigatran anticoagulation and Stanford type A aortic dissection: lethal coincidence: case report with literature review. Acta Anaesthesiol Scand 2014; 58: 630-7.
26. Wychowski MK, Kouides PA. Dabigatran-induced gastrointestinal bleeding in an elderly patient with moderate renal impairment. Ann Pharmacother 2012; 46: e10.
27. Bouchard J, Ghannoum M, Bernier-Jean A, Williamson D, Kershaw G, Weatherburn C, Eris JM, Tran H, Patel JP, Roberts DM. Comparison of intermittent and continuous extracorporeal treatments for the enhanced elimination of dabigatran. Clin Toxicol (Phila) 2015; 53: 156-63.
28. Paul S, Hamouda D, Prashar R, Mbaso C, Khan A, Ali A, Shah S, Assaly R. Management of dabigatran-induced bleeding with continuous venovenous hemodialysis. Int J Hematol 2015; 101: 594-7.
29. Claisse G, Delavenne X, Masson I, Maillard N, Alamartine E, Mariat C. Venovenous haemodiafiltration for the management of dabigatran overdose in intensive care unit. Clin Kidney J 2015; 8: 199-201.
30. Montaruli B, Erroi L, Vitale C, Berutti S, Cosseddu D, Sivera P, Coglitore R, Marangella M, Migliardi M. Dabigatran overdose: case report of laboratory coagulation parameters and hemodialysis of an 85-year-old man. Blood Coagul Fibrinolysis 2015; 26: 225-9.
31. Kumar R, Smith RE, Henry BL. A review of and recommendations for the management of patients with life-threatening dabigatran-associated hemorrhage: a single-center university hospital experience. J Intensive Care Med 2014; PMID: 24668159. [Epub ahead of print].
32. Verma A, Chhibber V, Emhoff T, Klinger D. Promise and challenges of anticoagulation with dabigatran. Clin Kidney J 2012; 5: 336-8.
33. Cano EL, Miyares MA. Clinical challenges in a patient with dabigatran-induced fatal hemorrhage. Am J Geriatr Pharmacother 2012; 10: 160-3.
34. Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3: 692-4.
35. Eikelboom JW, Wallentin L, Connolly SJ, Ezekowitz M, Healey JS, Oldgren J, Yang S, Alings M, Kaatz S, Hohnloser SH, Diener HC, Franzosi MG, Huber K, Reilly P, Varrone J, Yusuf S. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation 2011; 123: 2363-72.
36. Stangier J, Stahle H, Rathgen K, Fuhr R. Pharmacokinetics and pharmacodynamics of the direct oral thrombin inhibitor dabigatran in healthy elderly subjects. Clin Pharmacokinet 2008; 47: 47-59.
37. Reilly PA, Lehr T, Haertter S, Connolly SJ, Yusuf S, Eikelboom JW, Ezekowitz MD, Nehmiz G, Wang S, Wallentin L. The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). J Am Coll Cardiol 2014; 63: 321-8.
38. Hawes EM, Deal AM, Funk-Adcock D, Gosselin R, Jeanneret C, Cook AM, Taylor JM, Whinna HC, Winkler AM, Moll S. Performance of coagulation tests in patients on therapeutic doses of dabigatran: a cross-sectional pharmacodynamic study based on peak and trough plasma levels. J Thromb Haemost 2013; 11: 1493-502.
39. Majeed A, Hwang HG, Connolly SJ, Eikelboom JW, Ezekowitz MD, Wallentin L, Brueckmann M, Fraessdorf M, Yusuf S, Schulman S. Management and outcomes of major bleeding during treatment with dabigatran or warfarin. Circulation 2013; 128: 2325-32.
40. Siegal DM, Garcia DA, Crowther MA. How I treat target-specific oral anticoagulant-associated bleeding. Blood 2014; 123: 1152-8.
41. Flibotte JJ, Hagan N, O'Donnell J, Greenberg SM, Rosand J. Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage. Neurology 2004; 63: 1059-64.
42. Cucchiara B, Messe S, Sansing L, Kasner S, Lyden P, CHANT Investigators Hematoma growth in oral anticoagulant related intracerebral hemorrhage. Stroke 2008; 39: 2993-6.
43. Liesenfeld KH, Staab A, Hartter S, Formella S, Clemens A, Lehr T. Pharmacometric characterization of dabigatran hemodialysis. Clin Pharmacokinet 2013; 52: 453-62.