Intracerebral haemorrhage associated with antithrombotic treatment: Translational insights from experimental studies

The Lancet Neurology

Volumn 12, Issue 4, 2013, Pages 394-405

  Lauer, Arne ^a,b   Pfeilschifter, Waltraud ^a   Schaffer, Chris B ^c   Lo, Eng H ^b   Foerch, Christian ^a,b  

^a GOETHE UNIVERSITY   (Germany)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

^c School of Chemical and Molecular Engineering   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLSALICYLIC ACID; ANTICOAGULANT AGENT; ANTIVITAMIN K; BLOOD CLOTTING FACTOR 10A INHIBITOR; CLOPIDOGREL; DABIGATRAN; FK 419; MELAGATRAN; PROTAMINE SULFATE; PROTHROMBIN COMPLEX; RECOMBINANT BLOOD CLOTTING FACTOR 7A; RIVAROXABAN; THROMBIN INHIBITOR; TRANEXAMIC ACID; UNCLASSIFIED DRUG; VITAMIN K GROUP; WARFARIN;

ANTICOAGULANT THERAPY; BLEEDING TIME; BRAIN HEMORRHAGE; CLINICAL PRACTICE; DRUG BINDING; DRUG EFFICACY; EVIDENCE BASED PRACTICE; HEMATOMA; HEMOSTASIS; HUMAN; INTERNATIONAL NORMALIZED RATIO; NONHUMAN; PRIORITY JOURNAL; PROTHROMBIN TIME; REVIEW; TRANSLATIONAL RESEARCH; TREATMENT OUTCOME;

ADMINISTRATION, ORAL; ANIMALS; CEREBRAL HEMORRHAGE; FIBRINOLYTIC AGENTS; HUMANS; TRANSLATIONAL MEDICAL RESEARCH; TREATMENT OUTCOME;

EID: 84875232430     PISSN: 14744422     EISSN: 14744465     Source Type: Journal    
DOI: 10.1016/S1474-4422(13)70049-8     Document Type: Review

References (99)

1. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001, 285:2370-2375.
2. Stead LG, Jain A, Bellolio MF, et al. Effect of anticoagulant and antiplatelet therapy in patients with spontaneous intra-cerebral hemorrhage: does medication use predict worse outcome?. Clin Neurol Neurosurg 2010, 112:275-281.
3. Flaherty ML Anticoagulant-associated intracerebral hemorrhage. Semin Neurol 2010, 30:565-572.
4. Vernooij MW, Haag MDM, van der Lugt A, et al. Use of antithrombotic drugs and the presence of cerebral microbleeds: the Rotterdam Scan Study. Arch Neurol 2009, 66:714-720.
5. Xi G, Keep RF, Hoff JT Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol 2006, 5:53-63.
6. Davis SM, Broderick J, Hennerici M, et al. Hematoma growth is a determinant of mortality and poor outcome after intracerebral hemorrhage. Neurology 2006, 66:1175-1181.
7. Broderick JP, Brott TG, Duldner JE, Tomsick T, Huster G Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day mortality. Stroke 1993, 24:987-993.
8. Aguilar MI, Hart RG, Kase CS, et al. Treatment of warfarin-associated intracerebral hemorrhage: literature review and expert opinion. Mayo Clin Proc 2007, 82:82-92.
9. Mayer SA, Davis SM, Skolnick BE, et al. Can a subset of intracerebral hemorrhage patients benefit from hemostatic therapy with recombinant activated factor VII?. Stroke 2009, 40:833-840.
10. Elliott J, Smith M The acute management of intracerebral hemorrhage: a clinical review. Anesth Analg 2010, 110:1419-1427.
11. Flaherty ML, Adeoye O, Sekar P, et al. The challenge of designing a treatment trial for warfarin-associated intracerebral hemorrhage. Stroke 2009, 40:1738-1742.
12. Kirkman MA, Allan SM, Parry-Jones AR Experimental intracerebral hemorrhage: avoiding pitfalls in translational research. J Cereb Blood Flow Metab 2011, 31:2135-2151.
13. Rane A, Lindh JD Pharmacogenetics of anticoagulants. Hum Genomics Proteomics 2010, 2010:754919.
14. Hirsh J, Poller L The international normalized ratio. A guide to understanding and correcting its problems. Arch Intern Med 1994, 154:282-288.
15. Friberg L, Rosenqvist M, Lip GYH Net clinical benefit of warfarin in patients with atrial fibrillation: a report from the Swedish atrial fibrillation cohort study. Circulation 2012, 125:2298-2307.
16. Franke CL, de Jonge J, van Swieten JC, op de Coul AA, van Gijn J Intracerebral hematomas during anticoagulant treatment. Stroke 1990, 21:726-730.
17. Huttner HB, Schellinger PD, Hartmann M, et al. Hematoma growth and outcome in treated neurocritical care patients with intracerebral hemorrhage related to oral anticoagulant therapy: comparison of acute treatment strategies using vitamin K, fresh frozen plasma, and prothrombin complex concentrates. Stroke 2006, 37:1465-1470.
18. Flaherty ML, Tao H, Haverbusch M, et al. Warfarin use leads to larger intracerebral hematomas. Neurology 2008, 71:1084-1089.
19. Flibotte JJ, Hagan N, O'Donnell J, Greenberg SM, Rosand J Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage. Neurology 2004, 63:1059-1064.
20. Rosand J, Eckman MH, Knudsen KA, Singer DE, Greenberg SM The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage. Arch Intern Med 2004, 164:880-884.
21. Fang MC, Go AS, Chang Y, et al. Thirty-day mortality after ischemic stroke and intracranial hemorrhage in patients with atrial fibrillation on and off anticoagulants. Stroke 2012, 43:1795-1799.
22. Flaherty ML, Haverbusch M, Sekar P, et al. Location and outcome of anticoagulant-associated intracerebral hemorrhage. Neurocrit Care 2006, 5:197-201.
23. Toyoda K, Yasaka M, Nagata K, et al. Antithrombotic therapy influences location, enlargement, and mortality from intracerebral hemorrhage. The Bleeding with Antithrombotic Therapy (BAT) Retrospective Study. Cerebrovasc Dis 2009, 27:151-159.
24. Dowlatshahi D, Butcher KS, Asdaghi N, et al. Poor prognosis in warfarin-associated intracranial hemorrhage despite anticoagulation reversal. Stroke 2012, 43:1812-1817.
25. Hua Y, Keep RF, Hoff JT, Xi G Brain injury after intracerebral hemorrhage: the role of thrombin and iron. Stroke 2007, 38:759-762.
26. Levine JM, Snider R, Finkelstein D, et al. Early edema in warfarin-related intracerebral hemorrhage. Neurocrit Care 2007, 7:58-63.
27. Song T, Kim J, Lee HS, et al. The frequency of cerebral microbleeds increases with CHADS(2) scores in stroke patients with non-valvular atrial fibrillation. Eur J Neurol 2012, published online Oct 11. 10.1111/ene.12003.
28. Wong KS, Chan YL, Liu JY, Gao S, Lam WWM Asymptomatic microbleeds as a risk factor for aspirin-associated intracerebral hemorrhages. Neurology 2003, 60:511-513.
29. Lee S, Ryu W, Roh J Cerebral microbleeds are a risk factor for warfarin-related intracerebral hemorrhage. Neurology 2009, 72:171-176.
30. Lovelock CE, Cordonnier C, Naka H, et al. Antithrombotic drug use, cerebral microbleeds, and intracerebral hemorrhage: a systematic review of published and unpublished studies. Stroke 2010, 41:1222-1228.
31. Foerch C, Arai K, Jin G, et al. Experimental model of warfarin-associated intracerebral hemorrhage. Stroke 2008, 39:3397-3404.
32. Illanes S, Zhou W, Heiland S, Markus Z, Veltkamp R Kinetics of hematoma expansion in murine warfarin-associated intracerebral hemorrhage. Brain Res 2010, 1320:135-142.
33. Lauer A, Cianchetti FA, van Cott EM, et al. Anticoagulation with the oral direct thrombin inhibitor dabigatran does not enlarge hematoma volume in experimental intracerebral hemorrhage. Circulation 2011, 124:1654-1662.
34. Foerch C, Arai K, van Cott EM, van Leyen K, Lo EH Rapid reversal of anticoagulation reduces hemorrhage volume in a mouse model of warfarin-associated intracerebral hemorrhage. J Cereb Blood Flow Metab 2009, 29:1015-1021.
35. Illanes S, Zhou W, Schwarting S, Heiland S, Veltkamp R Comparative effectiveness of hemostatic therapy in experimental warfarin-associated intracerebral hemorrhage. Stroke 2011, 42:191-195.
36. Schlunk F, van Cott EM, Hayakawa K, Pfeilschifter W, Lo EH, Foerch C Recombinant activated coagulation factor VII and prothrombin complex concentrates are equally effective in reducing hematoma volume in experimental warfarin-associated intracerebral hemorrhage. Stroke 2012, 43:246-249.
37. Zhou W, Schwarting S, Illanes S, et al. Hemostatic therapy in experimental intracerebral hemorrhage associated with the direct thrombin inhibitor dabigatran. Stroke 2011, 42:3594-3599.
38. Zhou W, Zorn M, Nawroth P, et al. Hemostatic therapy in experimental intracerebral hemorrhage associated with rivaroxaban. Stroke 2013, published online Jan 22. 10.1161/STROKEAHA.112.675231.
39. Choudhri TF, Hoh BL, Solomon RA, Connolly ES, Pinsky DJ Use of a spectrophotometric hemoglobin assay to objectively quantify intracerebral hemorrhage in mice. Stroke 1997, 28:2296-2302.
40. Mihara K, Aoki T, Moriguchi A, et al. Prohemorrhagic and bleeding time activities of recombinant tissue plasminogen activator, heparin, aspirin, and a glycoprotein IIb/IIIa antagonist. J Neurotrauma 2005, 22:1362-1373.
41. Lauer A, Schlunk F, van Cott EM, Steinmetz H, Lo EH, Foerch C Antiplatelet pretreatment does not increase hematoma volume in experimental intracerebral hemorrhage. J Cereb Blood Flow Metab 2011, 31:1736-1742.
42. Zhou Z, Qu F, Zhang C Systemic administration of argatroban inhibits protease-activated receptor-1 expression in perihematomal tissue in rats with intracerebral hemorrhage. Brain Res Bull 2011, 86:235-238.
43. Xi G, Wagner KR, Keep RF, et al. Role of blood clot formation on early edema development after experimental intracerebral hemorrhage. Stroke 1998, 29:2580-2586.
44. Nishimura N, Schaffer CB, Friedman B, Tsai PS, Lyden PD, Kleinfeld D Targeted insult to subsurface cortical blood vessels using ultrashort laser pulses: three models of stroke. Nat Methods 2006, 3:99-108.
45. Rosidi NL, Zhou J, Pattanaik S, et al. Cortical microhemorrhages cause local inflammation but do not trigger widespread dendrite degeneration. PLoS One 2011, 6:e26612.
46. Cianchetti FA, Nishimura N, Schaffer CB. Stimulus-evoked calcium transients in somatosensory cortex are inhibited after a nearby microhemorrhage. Biomedical Optics, OSA Technical Digest, 2010; paper JMA93.
47. Leira R, Dávalos A, Silva Y, et al. Early neurologic deterioration in intracerebral hemorrhage: predictors and associated factors. Neurology 2004, 63:461-467.
48. Goldstein JN, Thomas SH, Frontiero V, et al. Timing of fresh frozen plasma administration and rapid correction of coagulopathy in warfarin-related intracerebral hemorrhage. Stroke 2006, 37:151-155.
49. Makris M, Greaves M, Phillips WS, Kitchen S, Rosendaal FR, Preston EF Emergency oral anticoagulant reversal: the relative efficacy of infusions of fresh frozen plasma and clotting factor concentrate on correction of the coagulopathy. Thromb Haemost 1997, 77:477-480.
50. Boulis NM, Bobek MP, Schmaier A, Hoff JT Use of factor IX complex in warfarin-related intracranial hemorrhage. Neurosurgery 1999, 45:1113-1118.
51. Pinner NA, Hurdle AC, Oliphant C, Reaves A, Lobo B, Sills A Treatment of warfarin-related intracranial hemorrhage: a comparison of prothrombin complex concentrate and recombinant activated factor VII. World Neurosurg 2010, 74:631-635.
52. Kuwashiro T, Yasaka M, Itabashi R, et al. Effect of prothrombin complex concentrate on hematoma enlargement and clinical outcome in patients with anticoagulant-associated intracerebral hemorrhage. Cerebrovasc Dis 2011, 31:170-176.
53. Voils SA, Baird B Systematic review: 3-factor versus 4-factor prothrombin complex concentrate for warfarin reversal: does it matter?. Thromb Res 2012, 6:833-840.
54. Mayer SA, Brun NC, Begtrup K, et al. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med 2008, 358:2127-2137.
55. Monroe DM Further understanding of recombinant activated factor VII mode of action. Semin Hematol 2008, 45:S7-S11.
56. Kawai N, Nakamura T, Nagao S Early hemostatic therapy using recombinant factor VIIa in a collagenase-induced intracerebral hemorrhage model in rats. Acta Neurochir Suppl 2006, 96:212-217.
57. Di Nisio M, Middeldorp S, Büller HR Direct thrombin inhibitors. N Engl J Med 2005, 353:1028-1040.
58. Stangier J Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet 2008, 47:285-295.
59. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009, 361:1139-1151.
60. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011, 365:883-891.
61. Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011, 365:981-992.
62. Weimar C, Hohnloser SH, Eikelboom JW, Diener H Preventing cardioembolic stroke in atrial fibrillation with dabigatran. Curr Neurol Neurosci Rep 2012, 12:17-23.
63. Hart RG, Diener H, Yang S, et al. Intracranial hemorrhage in atrial fibrillation patients during anticoagulation with warfarin or dabigatran: the RE-LY trial. Stroke 2012, 43:1511-1517.
64. Eriksson BI, Dahl OE, Ahnfelt L, et al. Dose escalating safety study of a new oral direct thrombin inhibitor, dabigatran etexilate, in patients undergoing total hip replacement: BISTRO I. J Thromb Haemost 2004, 2:1573-1580.
65. Watanabe M, Siddiqui FM, Qureshi AI Incidence and management of ischemic stroke and intracerebral hemorrhage in patients on dabigatran etexilate treatment. Neurocrit Care 2012, 16:203-209.
66. del Zoppo GJ, Eliasziw M New options in anticoagulation for atrial fibrillation. N Engl J Med 2011, 365:952-953.
67. Nielsen VG, Cohen BM, Cohen E Effects of coagulation factor deficiency on plasma coagulation kinetics determined via thrombelastography: critical roles of fibrinogen and factors II, VII, X and XII. Acta Anaesthesiol Scand 2005, 49:222-231.
68. Stangier J, Rathgen K, Stähle 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, 49:259-268.
69. van Ryn J, Stangier J, Haertter S, et al. Dabigatran etexilate-a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost 2010, 103:1116-1127.
70. Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation 2011, 124:1573-1579.
71. Battinelli EM Reversal of new oral anticoagulants. Circulation 2011, 124:1508-1510.
72. Van Ryn J, Litzenburger T, Gan G, Coble K, Schurer J. In vitro characterization, pharmacokinetics and reversal of supratherapeutic doses of dabigatran-induced bleeding in rats by a specific antibody fragment antidote to dabigatran. American Heart Association Scientific Sessions 2012; Los Angeles; Nov 3-7, 2012. Oral presentation 9928.
73. Elg M, Carlsson S, Gustafsson D Effects of agents, used to treat bleeding disorders, on bleeding time prolonged by a very high dose of a direct thrombin inhibitor in anesthesized rats and rabbits. Thromb Res 2001, 101:159-170.
74. Sørensen B, Ingerslev J A direct thrombin inhibitor studied by dynamic whole blood clot formation. Haemostatic response to ex-vivo addition of recombinant factor VIIa or activated prothrombin complex concentrate. Thromb Haemost 2006, 96:446-453.
75. Elg M, Carlsson S, Gustafsson D Effect of activated prothrombin complex concentrate or recombinant factor VIIa on the bleeding time and thrombus formation during anticoagulation with a direct thrombin inhibitor. Thromb Res 2001, 101:145-157.
76. Broos K, Feys HB, De Meyer SF, Vanhoorelbeke K, Deckmyn H Platelets at work in primary hemostasis. Blood Rev 2011, 25:155-167.
77. Roquer J, Rodríguez Campello A, Gomis M, Ois A, Puente V, Munteis E Previous antiplatelet therapy is an independent predictor of 30-day mortality after spontaneous supratentorial intracerebral hemorrhage. J Neurol 2005, 252:412-416.
78. Saloheimo P, Ahonen M, Juvela S, Pyhtinen J, Savolainen E, Hillbom M Regular aspirin-use preceding the onset of primary intracerebral hemorrhage is an independent predictor for death. Stroke 2006, 37:129-133.
79. Naidech AM, Jovanovic B, Liebling S, et al. Reduced platelet activity is associated with early clot growth and worse 3-month outcome after intracerebral hemorrhage. Stroke 2009, 40:2398-2401.
80. Naidech AM, Rosenberg NF, Bernstein RA, Batjer HH Aspirin use or reduced platelet activity predicts craniotomy after intracerebral hemorrhage. Neurocrit Care 2011, 15:442-446.
81. Campbell PG, Yadla S, Sen AN, Jallo J, Jabbour P Emergency reversal of clopidogrel in the setting of spontaneous intracerebral hemorrhage. World Neurosurg 2011, 76:100-104.
82. Moussouttas M, Malhotra R, Fernandez L, et al. Role of antiplatelet agents in hematoma expansion during the acute period of intracerebral hemorrhage. Neurocrit Care 2010, 12:24-29.
83. Sansing LH, Messe SR, Cucchiara BL, Cohen SN, Lyden PD, Kasner SE Prior antiplatelet use does not affect hemorrhage growth or outcome after ICH. Neurology 2009, 72:1397-1402.
84. Foerch C, Sitzer M, Steinmetz H, Neumann-Haefelin T Pretreatment with antiplatelet agents is not independently associated with unfavorable outcome in intracerebral hemorrhage. Stroke 2006, 37:2165-2167.
85. Thompson BB, Béjot Y, Caso V, et al. Prior antiplatelet therapy and outcome following intracerebral hemorrhage: a systematic review. Neurology 2010, 75:1333-1342.
86. Creutzfeldt CJ, Weinstein JR, Longstreth WT, Becker KJ, McPharlin TO, Tirschwell DL Prior antiplatelet therapy, platelet infusion therapy, and outcome after intracerebral hemorrhage. J Stroke Cerebrovasc Dis 2009, 18:221-228.
87. Ducruet AF, Hickman ZL, Zacharia BE, et al. Impact of platelet transfusion on hematoma expansion in patients receiving antiplatelet agents before intracerebral hemorrhage. Neurol Res 2010, 32:706-710.
88. Naidech AM, Liebling SM, Rosenberg NF, et al. Early platelet transfusion improves platelet activity and may improve outcomes after intracerebral hemorrhage. Neurocrit Care 2012, 16:82-87.
89. de Gans K, de Haan RJ, Majoie CB, et al. PATCH: platelet transfusion in cerebral haemorrhage: study protocol for a multicentre, randomised, controlled trial. BMC Neurol 2010, 10:19.
90. Koltai K, Feher G, Kenyeres P, et al. Relation of platelet aggregation and fibrinogen levels to advancing age in aspirin- and thienopyridine-treated patients. Clin Hemorheol Microcirc 2008, 40:295-302.
91. Monroe DM, Hoffman M, Roberts HR Platelets and thrombin generation. Arterioscler Thromb Vasc Biol 2002, 22:1381-1389.
92. Bouchard BA, Shatos MA, Tracy PB Human brain pericytes differentially regulate expression of procoagulant enzyme complexes comprising the extrinsic pathway of blood coagulation. Arterioscler Thromb Vasc Biol 1997, 17:1-9.
93. Rosenberg GA, Mun-Bryce S, Wesley M, Kornfeld M Collagenase-induced intracerebral hemorrhage in rats. Stroke 1990, 21:801-807.
94. Smyth SS, McEver RP, Weyrich AS, et al. Platelet functions beyond hemostasis. J Thromb Haemost 2009, 7:1759-1766.
95. Tsakiris DA, Scudder L, Hodivala-Dilke K, Hynes RO, Coller BS Hemostasis in the mouse (Mus musculus): a review. Thromb Haemost 1999, 81:177-188.
96. Lee JM, Zhai G, Liu Q, et al. Vascular permeability precedes spontaneous intracerebral hemorrhage in stroke-prone spontaneously hypertensive rats. Stroke 2007, 38:3289-3291.
97. Kaatz S, Kouides PA, Garcia DA, et al. Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors. Am J Hematol 2012, 87(suppl 1):S141-S145.
98. Steiner T, Petersson J, Al-Shahi Salman R, et al. European research priorities for intracerebral haemorrhage. Cerebrovasc Dis 2011, 32:409-419.
99. Ruggeri ZM Platelet adhesion under flow. Microcirculation 2009, 16:58-83.