Skip to main content

Advertisement

Log in

Prothrombotic states that predispose to stroke

  • Published:
Current Treatment Options in Neurology Aims and scope Submit manuscript

Opinion statement

Hereditary prothrombotic states of clinical importance include factor V Leiden, the prothrombin 20210A mutation, deficiencies of protein C, protein S, or antithrombin, sickle cell disease, and hyperhomocysteinemia. Major acquired prothrombotic states include cancer, myeloproliferative disorders, the antiphospholipid syndrome, and heparin-induced thrombocytopenia. Because most of the hereditary prothrombic states are not established risk factors for arterial thrombosis, routine laboratory testing in most patients with ischemic stroke should be limited to complete blood count, lupus anticoagulant, anticardiolipin antibodies, and plasma total homocysteine. Additional testing for factor V Leiden, prothrombin 20210A, antithrombin, protein C, and protein S may be indicated for patients under the age of 50 or those with paradoxical cerebral embolism. The treatment of acute ischemic stroke in patients with prothrombotic states is similar to that in patients without an identifiable prothrombotic condition, and may include antiplatelet agents, anticoagulants, or thrombolytic therapy in patients who otherwise meet eligibility criteria. The potential benefit of chronic anticoagulation therapy for the primary or secondary prevention of stroke in patients with prothrombotic states has not been addressed in controlled clinical trials. Specific therapeutic approaches for the prevention of stroke are established for patients with sickle cell disease, myeloproliferative disorders, and heparininduced thrombocytopenia, and are under investigation for hyperhomocysteinemia and the antiphospholipid syndrome.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Kearon C, Crowther M, Hirsh J: Management of patients with hereditary hypercoagulable disorders. Ann Rev Med 2000, 51:169–185. An excellent overview of the hereditary prothrombotic states and their clinical management.

    Article  PubMed  CAS  Google Scholar 

  2. Martinelli I: Risk factors in venous thromboembolism. Thromb Haemost 2001, 86:395–403.

    PubMed  CAS  Google Scholar 

  3. Vandermeer FJM, Koster T, Vandenbroucke JP, et al.: The Leiden thrombophilia study (LETS). Thromb Haemost 1997, 78:631–635. A summary of the Leiden Thrombophilia Study, which was a large case-control study that provided definitive evidence that factor V Leiden and other hereditary prothrombotic states are risk factors for venous thromboembolism.

    CAS  Google Scholar 

  4. Reiner AP, Siscovick DS, Rosendaal FR: Hemostatic risk factors and arterial thrombotic disease. Thromb Haemost 2001, 85:584–595. A thorough review of the epidemiologic evidence for an association between hemostatic risk factors and ischemic stroke or myocardial infarction.

    PubMed  CAS  Google Scholar 

  5. Margaglione M, D’Andrea G, Giuliani N, et al.: Inherited prothrombotic conditions and premature ischemic stroke: sex difference in the association with factor V Leiden. Arterioscler ThrombVasc Biol 1999, 19:1751–1756.

    CAS  Google Scholar 

  6. Destefano V, Chiusolo P, Paciaroni K, et al.: Prothrombin G20210A mutant genotype is a risk factor for cerebrovascular ischemic disease in young patients. Blood 1998, 91:3562–3565.

    CAS  Google Scholar 

  7. Steinberg MH: Management of sickle cell disease. N Engl J Med 1999, 340:1021–1030.

    Article  PubMed  CAS  Google Scholar 

  8. Ohene-Frempong K, Weiner SJ, Sleeper LA, et al.: Cerebrovascular accidents in sickle cell disease: rates and risk factors. Blood 1998, 91:288–294.

    PubMed  CAS  Google Scholar 

  9. Mudd SH, Finkelstein JD, Refsum H, et al.: Homocysteine and its disulfide derivatives: a suggested consensus terminology. Arterioscler Thromb Vasc Biol 2000, 20:1704–1706.

    PubMed  CAS  Google Scholar 

  10. Selhub J: Homocysteine metabolism. Ann Rev Med 1999, 19:217–246.

    CAS  Google Scholar 

  11. Eikelboom JW, Lonn E, Genest JJ, et al.: Homocyst(e)ine and cardiovascular disease: a critical review of the epidemiologic evidence. Ann Intern Med 1999, 131:363–375. A systematic review of retrospective and prospective studies examining the association between hyperhomocysteinemia, cardiovascular disease, and cerebrovascular disease.

    PubMed  CAS  Google Scholar 

  12. Eikelboom JW, Hankey GJ, Anand SS, et al.: Association between high homocyst(e)ine and ischemic stroke due to large- and small-artery disease but not other etiologic subtypes of ischemic stroke. Stroke 2000, 31:1069–1075.

    PubMed  CAS  Google Scholar 

  13. Joyce DE: The contribution of prothrombotic states to cancer-related stroke. Semin Cerebrovasc Dis Stroke 2002, In press.

  14. Cortelazzo S, Viero P, Finazzi G, et al.: Incidence and risk factors for thrombotic complications in a historical cohort of 100 patients with essential thrombocythemia. J Clin Oncol 1990, 8:556–562.

    PubMed  CAS  Google Scholar 

  15. Levine JS, Branch DW, Rauch J: The antiphospholipid syndrome. N Engl J Med 2002, 346:752–763. An authoritative review of current issues related to diagnosis and management of patients with the antiphospholipid syndrome.

    Article  PubMed  CAS  Google Scholar 

  16. 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.

    Article  PubMed  CAS  Google Scholar 

  17. Petri M: Epidemiology of the antiphospholipid antibody syndrome. J Autoimmun 2000, 15:145–151.

    Article  PubMed  CAS  Google Scholar 

  18. Tuhrim S, Rand JH, Wu XX, et al.: Elevated anticardiolipin antibody titer is a stroke risk factor in a multiethnic population independent of isotype or degree of positivity. Stroke 1999, 30:1561–1565.

    PubMed  CAS  Google Scholar 

  19. Brey RL, Abbott RD, Curb JD, et al.: Beta(2)-glycoprotein I-dependent anticardiolipin antibodies and risk of ischemic stroke and myocardial infarction: the Honolulu heart program. Stroke 2001, 32:1701–1706.

    PubMed  CAS  Google Scholar 

  20. Ginsburg KS, Liang MH, Newcomer L, et al.: Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis. Ann Intern Med 1992, 117:997–1002.

    PubMed  CAS  Google Scholar 

  21. Finazzi G, Brancaccio V, Moia M, et al.: Natural history and risk factors for thrombosis in 360 patients with antiphospholipid antibodies: a four-year prospective study from the Italian Registry. Am J Med 1996, 100:530–536.

    Article  PubMed  CAS  Google Scholar 

  22. Warkentin TE: Heparin-induced thrombocytopenia: a clinicopathologic syndrome. Thromb Haemost 1999, 82:439–447. An outstanding overview of heparin-induced thrombocytopenia that was written by one of the pioneering investigators who helped define this clinical syndrome.

    PubMed  CAS  Google Scholar 

  23. Warkentin TE, Kelton JG: Delayed-onset heparininduced thrombocytopenia and thrombosis. Ann Intern Med 2002, 135:502–506.

    Google Scholar 

  24. Jacques PF, Selhub J, Bostom AG, et al.: The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Eng J Med 1999, 340:1449–1454.

    Article  CAS  Google Scholar 

  25. Brott T, Bogousslavsky J: Treatment of acute ischemic stroke. N Engl J Med 2000, 343:710–722.

    Article  PubMed  CAS  Google Scholar 

  26. Clarke R, Armitage J: Vitamin supplements and cardiovascular risk: review of the randomized trials of homocysteine-lowering vitamin supplements. Semin Thromb Hemost 2000, 26:341–348.

    Article  PubMed  CAS  Google Scholar 

  27. Ware RE, Zimmerman SA, Schultz WH: Hydroxyurea as an alternative to blood transfusions for the prevention of recurrent stroke in children with sickle cell disease. Blood 1999, 94:3022–3026.

    PubMed  CAS  Google Scholar 

  28. Refsum H, Ueland PM, Nygård O, Vollset SE: Homocysteine and cardiovascular disease. Annu Rev Med 1998, 49:31–62.

    Article  PubMed  CAS  Google Scholar 

  29. Malinow MR, Bostom AG, Krauss RM: Homocyst(e)ine, diet, and cardiovascular diseases: a statement for healthcare professionals from the Nutrition Committee, American Heart Association. Circulation 1999, 99:178–182.

    PubMed  CAS  Google Scholar 

  30. Salen DN, Daudelin HD, Levine HL, et al.: Antithrombotic therapy in valvular heart disease. Chest 2001, 119:207S-219S.

    Article  Google Scholar 

  31. Cortelazzo S, Finazzi G, Ruggeri M, et al.: Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med 1995, 332:1132–1136.

    Article  PubMed  CAS  Google Scholar 

  32. Regev A, Stark P, Blickstein D, Lahav M: Thrombotic complications in essential thrombocythemia with relatively low platelet counts. Am J Hematol 1997, 56:168–172.

    Article  PubMed  CAS  Google Scholar 

  33. Pearson TC, Wetherley-Mein G: Vascular occlusive episodes and venous haematocrit in primary proliferative polycythaemia. Lancet 1978, 2:1219–1222.

    Article  PubMed  CAS  Google Scholar 

  34. Rosove MH, Brewer PMC: Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients. Ann Intern Med 1992, 117:303–308.

    PubMed  CAS  Google Scholar 

  35. Khamashta MA, Cuadrado MJ, Mujic F, et al.: The management of thrombosis in the antiphospholipidantibody syndrome. N Engl J Med 1995, 332:993–997.

    Article  PubMed  CAS  Google Scholar 

  36. Mohr JP, Thompson JL, Lazar RM, et al.: Warfarinaspirin: a comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med 1915, 345:1444–1451.

    Article  Google Scholar 

  37. Moll S, Ortel TL: Monitoring warfarin therapy in patients with lupus anticoagulants. Ann Intern Med 1997, 127:177–185.

    PubMed  CAS  Google Scholar 

  38. Tardy-Poncet B, Tardy B, Reynaud J, et al.: Efficacy and safety of danaparoid sodium (ORG 10172) in critically ill patients with heparin-associated thrombocytopenia. Chest 1999, 115:1616–1620.

    Article  PubMed  CAS  Google Scholar 

  39. Hirsh J, Dalen J, Anderson DR, et al.: Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 2001, 119:8S-21S.

    Article  PubMed  CAS  Google Scholar 

  40. Adams RJ: Stroke prevention in sickle cell disease. Curr Opin Hematol 2000, 7:101–105. A thorough review of current strategies for the primary and secondary prevention of stroke in patients with sickle cell disease.

    Article  PubMed  CAS  Google Scholar 

  41. Nietert PJ, Abboud MR, Silverstein MD, Jackson SM: Bone marrow transplantation versus periodic prophylactic blood transfusion in sickle cell patients at high risk of ischemic stroke: a decision analysis. Blood 2000, 95:3057–3064.

    PubMed  CAS  Google Scholar 

  42. Greist A: The role of blood component removal in essential and reactive thrombocytosis. Ther Apher 2002, 6:36–44.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hiatt, B.K., Lentz, S.R. Prothrombotic states that predispose to stroke. Curr Treat Options Neurol 4, 417–425 (2002). https://doi.org/10.1007/s11940-002-0009-1

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11940-002-0009-1

Keywords

Navigation