Hostname: page-component-7b7567c8c-fvjsw Total loading time: 0 Render date: 2026-11-13T11:26:10.849Z Has data issue: false hasContentIssue false
  • English
  • Français

Hypercoagulable States and Stroke: A Selective Review

Published online by Cambridge University Press:  07 November 2014

Steven R. Levine
Get accessRights & Permissions [Opens in a new window]

Abstract

Blood disorders have been implicated in ~5% to 10% of ischemic stroke, with an increased frequency in younger patients. Most disorders are associated with an increased thrombotic tendency and, therefore, an increased risk of ischemic stroke. Less commonly, a bleeding diathesis may predispose a patient to intracranial hemorrhage. While many conditions predisposing to thrombosis have been associated with stroke, there are relatively few prospective, epidemiological studies addressing hypercoagulable states and arterial stroke compared with the number of studies on the genetic thrombophilias, which are predominantly associated with venous thrombosis. When ordering tests of coagulation in stroke patients, one should keep in mind whether the results will influence therapy and/or patient outcome. It is generally not advocated to screen all stroke patients for a “hypercoagulable workup”. Typically, patients to be screened for coagulation defects will have a prior history of one or more unexplained thromboembolic events. The yield for diagnosing a hypercoagulable state is typically greatest for young stroke patients or those with a family history of thrombosis and who have no other explanations for their stroke (cryptogenic stroke). The yield in typically low in unselected ischemic stroke patients and older patients. Treatment of a first stroke with a documented hypercoagulable state is typically long-term or indefinite duration warfarin, although there is a paucity of clinical trial data supporting this clinical approach.

Information

Type
Review Articles
Information
CNS Spectrums , Volume 10 , Issue 7 , July 2005, pp. 567 - 578
Copyright
Copyright © Cambridge University Press 2005

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

REFERENCES

1.Levine, SR, Tietjen, GE, Dafer, R, Feldmann, E. Hematologic abnormalities and stroke. In: Ginsberg, M, Bogousslavsky, J, eds. Cerebrovascular Disease: Pathology, Diagnosis, and Management. Boston, Mass: Blackwell Science; 1998:1698–1726.Google Scholar
2.Bushnell, CD, Goldstein, LB. Diagnostic testing for coagulopathies in patients with ischemic stroke. Stroke. 2000;31:3067–3078.Google Scholar
3.Kannel, WB, Wolf, PA, Castelli, WP, D'Agostino, RB. Fibrinogen and risk of cardiovascular disease. The Framingham Study. JAMA. 1987;258:1183–1186.Google Scholar
4.Landi, G, D'Angelo, A, Boccardi, E, et al.Hypercoagulability in acute stroke: prognostic significance. Neurology. 1987;37:1667–1671.Google Scholar
5.Bushnell, CD, Lentz, CR. Hypercoagulable states and cerebrovascular disease. MedLink website. Available at: http://www.medlink.com/MedLinkContent.asp. Accessed on 02 30, 2005.Google Scholar
6.Egeberg, O. Inherited antithrombin deficiency causing thrombophilia. Thromb Diath Haemorrh. 1965;13:516–530.Google ScholarPubMed
7.Lechat, P, Mas, JL, Lascault, G, et al.Prevalence of patent foramen ovale in patients with stroke. N Engl J Med. 1988;318:1148–1152.Google Scholar
8.De Stefano, V, Finazzi, G, Mannucci, PM. Inherited thrombophilia: pathogenesis, clinical syndromes, and management. Blood. 1996;87:3531–3544.Google Scholar
9.Rosenberg, RD, Aird, WC. Vascular-bed–specific hemostasis and hypercoagulable states. N Engl J Med. 1999;340:1555–1564.Google Scholar
10.Boinot, C, Borgel D, Kitzis, Guicheteau, M, Aiach, M, Alhenc-Gelas, M. Familial thrombophilia is an oligogenetic disease: involvement of the prothrombin G20210A, PROC, and PROS gene mutations. Blood Coagul Fibrinolysis. 2003;14:191–196.Google Scholar
11.Furie, K, Kelly, PJ, Kistler, JP. Coagulation Studies. In: Chaturvedi, S, Levine, SR, eds. Transient Ischemic Attacks. Malden, Mass: Futura Publishing Co; 2004:214–231.Google Scholar
12.Triplett, DA. Protean clinical presentation of antiphospholipid-protein antibodies (APA). Thromb Haemost. 1995;74:329–337.Google Scholar
13.Wilson, WA, Gharavi, AE, Koike, T, et al.International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an International Workshop. Arthritis Rheum. 1999;42:1309–1311.Google Scholar
14.Levine, SR, Brey, RL, Tilley, BC, et al.Antiphospholipid antibodies and subsequent thrombo-occlusive events in patients with ischemic stroke. JAMA. 2004;291:576–584.Google Scholar
15.Jacobs, BS, Levine, SR. Antiphospholipid antibody syndrome. Curr Treat Options Neurol. 2000;2:449–457.Google Scholar
16.Tanne, D, Levine, SR, Kittner, SJ. Epidemiology of antiphospholipid antibodies and vascular disease. In: Levine, SR, Brey, RL, eds. Clinical Approach to Antiphospholipid Antibodies. Boston, Mass: Butterworth Heinemann; 2000:1–18.Google Scholar
17.Wasserman, A, Neisser, A, Bruck, C. Eine diagnostische reaktion bei syphilis. Dtsch Med Wochensch. 1906;32:745–746.CrossRefGoogle Scholar
18.Lockshin, MD, Sammaritano, LR, Schwartzman, S. Validation of the Sapporo criteria for antiphospholipid syndrome. Arthritis Rheum. 2000;43:440–443.Google Scholar
19.Brey, RL, Chapman, J, Levine, SR, et al.Stroke and the antiphospholipid syndrome: consensus meeting Taormina 2002. Lupus. 2003;12:508–513.Google Scholar
20.Ginsberg, JS, Wells, PS, Brilledwards, P, et al.Antiphospholipid antibodies and venous thromboembolism. Blood. 1995;86:3685–3691.CrossRefGoogle ScholarPubMed
21.Greaves, M, Cohen, H, Machin, SJ, Mackie, I. Guidelines on the investigation and management of the antiphospholipid syndrome. Br J Haematol. 2000;109:704–715.Google Scholar
22.Anticardiolipin antibodies are an independent risk factor for first ischemic stroke. The Antiphospholipid Antibodies in Stroke Study (APASS) Group. Neurology. 1993;43:2069–2073.Google Scholar
23.Bertina, RM. Factor V Leiden and other coagulation factor mutations affecting thrombotic risk. Clin Chem. 1997;43:1678–1683.CrossRefGoogle ScholarPubMed
24.Dahlback, B. Resistance to activated protein C as risk factor for thrombosis: molecular mechanisms, laboratory investigation, and clinical management. Semin Hematol. 1997;34:217–234.Google Scholar
25.Fisher, M, Fernandez, JA, Ameriso, SF, et al.Activated protein C resistance in ischemic stroke not due to factor V arginine506–>glutamine mutation. Stroke. 1996;27:1163–1166.Google Scholar
26.van der Bom, JG, Bots, ML, Havetkate, F, et al.Reduced response to activated protein C is associated with increased risk for cerebrovascular disease. Ann Intern Med. 1996;125:265–269.Google Scholar
27.Poort, SR, Rosendaal, FR, Reitsma, PH, Bertina, RM. A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood. 1996;88:3698–3703.Google Scholar
28.Bertina, RM. The prothrombin 20210 G to A variation and thrombosis. Curr Opin Hematol. 1998;5:339–342.Google Scholar
29.Martinelli, I, Sacchi, E, Landi, G, Taioli, E, Duca, F, Mannucci, PM. High risk of cerebral-vein thrombosis in carriers of a prothrombin-gene mutation and in users of oral contraceptives. N Engl J Med. 1998;338:1793–1797.Google Scholar
30.Reuner, KH, Ruf, A, Grau, A, et al.Prothrombin gene G20210–>A transition is a risk factor for cerebral venous thrombosis. Stroke. 1998;29:1765–1769.Google Scholar
31.Landolfi, R. Bleeding and thrombosis in myeloproliterative disorders. Curr Opin Hematol. 1998;5:327–331.Google Scholar
32.Juul, K, Tybjearg-Hansen, A, Steffensen, R, Kofoed, S, Jensen, G, Nordestgaard, BG. Factor V Leiden: The Copenhagen City Heart Study and 2 meta-analyses. Blood. 2002;100:3–10.Google Scholar
33.Simioni, P, Prandoni, P, Lensing, AW, et al.The risk of recurrent venous thromboembolism in patients with an Arg506–>Gln mutation in the gene for factor V (factor V Leiden). N Engl J Med. 1997;336:399–403.Google Scholar
34.Tripodi, A, Mannucci, PM. Laboratory investigation of thrombophilia. Clin Chem. 2001;47:1597–1606.Google Scholar
35.Williamson, D, Brown, K, Luddington, R, Baglin, C, Baglin, T. Factor V Cambridge: a new mutation (Arg306–>Thr) associated with resistance to activated protein C. Blood. 1998;91:1140–1144.Google Scholar
36.van Boven, HH, Lane, DA. Antithrombin and its inherited deficiency states. Semin Hematol. 1997;34:188–204.Google Scholar
37.Smiles, AM, Jenny, NS, Tang, Z, Arnold, A, Cushman, M, Tracy, RP. No association of plasma prothrombin concentration or the G20210A mutation with incident cardiovascular disease: results from the Cardiovascular Health Study. Thromb Haemost. 2002;87:614–621.Google Scholar
38.Brey, RL, Stallworth, CL, McGlasson, DL, et al.Antiphospholipid antibodies and stroke in young women. Stroke. 2002;33:2396–2400.Google Scholar
39.Cho, C, Samuel, N, D'Olhaberriague, L, Brass, LM, Levine, SR. Coagulation-related causes of stroke. In: Samuels, MA, Feske, S, eds. Office Practice of Neurology. 2nd ed. New York, NY: Churchill Livingstone; 2003:353–358.Google Scholar
40.Harris, EN, Pierangeli, SS, Gharavi, AE. Diagnosis of the antiphospholipid syndrome: a proposal for use of laboratory tests. Lupus. 1998;7(suppl 2):S144–S148.Google Scholar
41.Gharavi, AE. Antiphospholipid cofactor. Stroke. 1992;23(suppl I):17–110.Google Scholar
42.Brey, RL, Abbott, RD, Curb, JD, et al.beta(2)-Glycoprotein 1-dependent anficardiolipin antibodies and risk of ischemic stroke and myocardial infarction: the honolulu heart program. Stroke. 2001;32(8):1701–1706.Google Scholar
43.Warkentin, TE, Chong, BH, Greinacher, A. Heparin-induced thrombocytopenia: towards consensus. Thromb Haemost. 1998;79:1–7.CrossRefGoogle ScholarPubMed
44.Rice, L. Heparin-induced thrombocytopenia: myths and misconceptions (that will cause trouble for you and your patient). Arch Intern Med. 2004;164:1961–1964.Google Scholar
45.Warkentin, TE. An overview of the heparin-induced thrombocytopenia syndrome. Semin Thromb Haemost. 2004;30:273–283.Google Scholar
46.LaMonte, MP, Brown, PM, Hursting, MJ. Stroke in patients with heparin-induced thrombocytopenia and the effect of argatroban therapy. Crit Care Med. 2004;32:976–980.Google Scholar
47.Ridker, PM, Hennekens, CH, Lindpaintner, K, et al.Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men. N Engl J Med. 1995;332:912–917.Google Scholar
48.Hankey, GJ, Eikelboom, JW, van Bockxmeer, FM, Lofthouse, G, Staples, N, Baker, RI. Inherited thromhophilia in ischemic stroke and its pathogenic subtypes. Stroke. 2001;32:1793–1799.Google Scholar
49.Salinger, MH, Feldman, TE. Patent foramen ovale: the missing link between deep venous thrombotic disease and embolic stroke. Dis Mon. 2005;51:94–103.Google Scholar
50.Pezzini, A, Del Zotto, E, Magoni, M, et al.Inherited thrombophilic disorders in young adults with ischemic stroke and patent foramen ovale. Stroke. 2003;34:28–33.Google Scholar
51.Bushnell, CD, Siddiqi, Z, Goldstein, LB. Improving patient selection for coagulopathy testing in the setting of acute ischemic stroke. Neurology. 2001;57:1333–1335.Google Scholar
52.Bushnell, C, Siddiqi, Z, Morgenlander, JC, Goldstein, LB, Use of specialized coagulation testing in the evaluation of patients with acute ischemic stroke. Neurology. 2001;56:624–627.Google Scholar
53.Jerrard-Dunne, P, Evans, A, McGovern, R, et al.Ethnic differences in markers of thrombophilia: implications for the investigation of ischemic stroke in multiethnic populations: the South London Ethnicity and Stroke Study. Stroke. 2003;34:1821–1826.Google Scholar
54.Tanne, D, D'Olhaberriague, L, Schultz, LR, et al.Anticardiolipin antibodies and their associations with cerebrovascular risk factors. Neurology. 1999;52:1368–1373.Google Scholar
55.Tanne, D, D'Olhaberriague, L, Trivedi, AM, Salowich-Palm, L, Schultz, LR, Levine, SR. Anticardiolipin antibodies and mortality in patients with ischemic stroke: a prospective follow-up study. Neuroepidemiology. 2002;21:93–99.Google Scholar
56.Ginsberg, JS. Management of venous thromboembolism. N Engl J Med. 1996;335:1816–1828.Google Scholar
57.Eichinger, S, Pabinger, I, Stumpflen, A, et al.The risk of recurrent venous thromboembolism in patients with and without factor V Leiden. Thromb Haemost. 1997;77:624–628.Google Scholar
58.Khamashta, MA, Cuadrado, MJ, Mujic, F, Taub, NA, Hunt, BJ, Hughes, GR. The management of thrombosis in the antiphospholipid-antibody syndrome. N Engl J Med. 1995;332:993–997.Google Scholar
59.Crowther, MA, Ginsberg, JS, Julian, J, et al.A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med. 2003;349:1133–1138.Google Scholar