Skip to main content
Log in

Hypercoagulable states and strokes

  • Published:
Current Atherosclerosis Reports Aims and scope Submit manuscript

Abstract

Several hematologic disorders and hemostatic defects increase risk of ischemic stroke. A common feature of these disorders is the creation of a prothrombotic state, now commonly referred to as “hypercoagulable state.” Hematologic diseases such as essential thrombocythemia, polycythemia vera, and thrombotic thrombocytopenic purpura clearly cause stroke. Effective treatment is now available for these disorders. Association of hemostatic defects with stroke risk is still at the investigational stage. Although a number of factors such as soluble thrombomodulin, fibrinogen, factor VIII, von Willebrand factor, and plasminogen activator inhibitor-I are associated with stroke risk, their predictive values remain unknown. Furthermore, causal relationship has not been established.

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.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Wu KK, Matijevic-Aleksic N: Molecular aspects of thrombosis and antithrombotic drugs. Crit Rev Clin Lab Sci 2005, 42:249–277.

    Article  PubMed  CAS  Google Scholar 

  2. Wu KK, Thiagarajan P: Endothelial cell function in hemostasis and thrombosis. Ann Rev Med 1996, 47:315–331.

    Article  PubMed  CAS  Google Scholar 

  3. Ishii H, Majerus PW: Thrombomodulin is present in human plasma and urine. J Clin Invest 1985, 76:2178–2181.

    Article  PubMed  CAS  Google Scholar 

  4. Wu KK, Matijevic-Aleksic N: Thrombomodulin: a linker of coagulation and fibrinolysis and predictor of risk of arterial thrombosis. Ann Med 2000, 32(Suppl 1):73–77.

    PubMed  CAS  Google Scholar 

  5. Salomaa V, Matei C, Aleksic N, et al.: Soluble thrombomodulin as a predictor of incident coronary heart disease and symptomless carotid artery atherosclerosis in the Atherosclerosis Risk in Communities (ARIC) Study: a case-cohort study. Lancet 1999, 353:1729–1734.

    Article  PubMed  CAS  Google Scholar 

  6. Olivot JM, Labreuche J, Aiach M, Amarenco P: Soluble thrombomodulin and brain infarction. Case-control and prospective study. Stroke 2004, 35:1946–1951.

    Article  PubMed  CAS  Google Scholar 

  7. Nomura E, Kohriyama T, Kozuka K, et al.: Significance of serum soluble thrombomodulin level in acute cerebral infarction. Eur J Neurol 2004, 11:329–334.

    Article  PubMed  CAS  Google Scholar 

  8. Salomaa V, Matei C, Aleksic N, et al.: Cross-sectional association of soluble thrombomodulin with mild peripheral artery disease; the ARIC study. Atherosclerosis Risk in Communities. Atherosclerosis 2001, 157:309–314.

    Article  PubMed  CAS  Google Scholar 

  9. Wu KK, Aleksic N, Ballantyne CM, et al.: Interaction between soluble thrombomodulin and intercellular adhesion molecule-1 in predicting risk of coronary heart disease. Circulation 2003, 107:1729–1732.

    Article  PubMed  CAS  Google Scholar 

  10. Ohlin AK, Norlund L, Marlar RA: Thrombomodulin gene variations and thromboembolic disease. Thromb Haemost 1997, 78:396–400.

    PubMed  CAS  Google Scholar 

  11. Wu KK, Aleksic N, Ahn C, et al.: Thrombomodulin Ala455Val polymorphism and risk of coronary heart disease. Circulation 2001, 103:1386–1389.

    PubMed  CAS  Google Scholar 

  12. Cole JW, Roberts SC, Gallagher M, et al.: Thrombomodulin Ala455Val Polymorphism and the risk of cerebral infarction in a biracial population: the Stroke Prevention in Young Women Study. BMC Neurol 2004, 4:21.

    Article  PubMed  CAS  Google Scholar 

  13. Landolfi R: Bleeding and thrombosis in myeloproliferative disorders. Curr Opin Hematol 1998, 5:327–331.

    Article  PubMed  CAS  Google Scholar 

  14. Jones AV, Kreil S, Zoi K, et al.: Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders. Blood 2005, 106:2162–2168.

    Article  PubMed  CAS  Google Scholar 

  15. Wu KK, Hoak JC: Spontaneous platelet aggregation in arterial insufficiency: mechanisms and implications. Thromb Haemost 1976, 35:702–711.

    PubMed  CAS  Google Scholar 

  16. ten Cate JW, Vos J, Oosterhius H, et al.: Spontaneous platelet aggregation in cerebrovascular disease. Thromb Haemost 1978, 39:223–229.

    PubMed  Google Scholar 

  17. Wu KK, Hoak JC: A new method for the quantitative detection of platelet aggregates in patients with arterial insufficiency. Lancet 1974, 2:924–926.

    Article  PubMed  CAS  Google Scholar 

  18. Tombul T, Atbas C, Anlar O: Hemostatic markers and platelet aggregation factors as predictive markers for type of stroke and neurological disability following cerebral infarction. J Clin Neurosci 2005, 12:429–434.

    Article  PubMed  CAS  Google Scholar 

  19. van Kooten F, Ciabattoni G, Patrono C, et al.: Platelet activation and lipid peroxidation in patients with acute ischemic stroke. Stroke 1997, 28:1557–1563.

    PubMed  Google Scholar 

  20. Konstantopoulos K, Grotta JC, Sills C, et al.: Shear-induced platelet aggregation in normal subjects and stroke patients. Thromb Haemost 1995, 74:1329–1334.

    PubMed  CAS  Google Scholar 

  21. Iwamoto T, Kubo H, Takasaki M: Platelet activation in the cerebral circulation in different subtypes of ischemic stroke and Binswanger’s disease. Stroke 1995, 26:52–56.

    PubMed  CAS  Google Scholar 

  22. Ridker PM, Hennekens CH, Schmitz C, et al.: PIA1/A2 polymorphism of platelet glycoprotein IIIa and risks of myocardial infarction, stroke, and venous thrombosis. Lancet 1997, 349:385–388.

    Article  PubMed  CAS  Google Scholar 

  23. Carlsson LE, Greinacher A, Spitzer C, et al.: Polymorphisms of the human platelet antigens HPA-1, HPA-2, HPA-3, and HPA-5 on the platelet receptors for fibrinogen (GPIIb/IIIa), von Willebrand factor (GPIb/IX), and collagen (GPIa/IIa) are not correlated with an increased risk for stroke. Stroke 1997, 28:1392–1395.

    PubMed  CAS  Google Scholar 

  24. Smith A, Patterson C, Yarnell J, et al.: Which hemostatic markers add to the predictive value of conventional risk factors for coronary heart disease and ischemic stroke? The Caerphilly Study. Circulation 2005, 112:3080–3087.

    Article  PubMed  Google Scholar 

  25. Markus HS, Hunt B, Palmer K, et al.: Markers of endothelial and hemostatic activation and progression of cerebral white matter hyperintensities: longitudinal results of the Austrian Stroke Prevention Study. Stroke 2005, 36:1410–1414.

    Article  PubMed  CAS  Google Scholar 

  26. Smith FB, Lee AJ, Fowkes FG, et al.: Hemostatic factors as predictors of ischemic heart disease and stroke in the Edinburgh Artery Study. Arterioscler Thromb Vasc Biol 1997, 17:3321–3325.

    PubMed  CAS  Google Scholar 

  27. Folsom AR, Rosamond WD, Shahar E, et al.: Prospective study of markers of hemostatic function with risk of ischemic stroke. Circulation 1999, 100:736–742.

    PubMed  CAS  Google Scholar 

  28. Tracy RP, Bovill EG, Yanez D, et al.: Fibrinogen and factor VIII, but not factor VII, are associated with measures of subclinical cardiovascular disease in the elderly: results from the Cardiovascular Health Study. Arterioscler Thromb Vasc Biol 1995, 15:1269–1279.

    PubMed  CAS  Google Scholar 

  29. Knuiman MW, Folsom AR, Chambless LE, et al.: Association of hemostatic variables with MRI-detected cerebral abnormalities: The Atherosclerosis Risk in Communities Study. Neuroepidemiology 2001, 20:96–104.

    Article  PubMed  CAS  Google Scholar 

  30. Maresca G, Di Blasio A, Marchioli R, et al.: Measuring plasma fibrinogen to predict stroke and myocardial infarction: an update. Arterioscler Thromb Vasc Biol 1999, 19:1368–1377.

    PubMed  CAS  Google Scholar 

  31. Danesh J, Lewington S, Thompson SG, et al.: Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. JAMA 2005, 294:1799–1809.

    Article  PubMed  CAS  Google Scholar 

  32. 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 Thromb Vasc Biol 1999, 19:1751–1756.

    PubMed  CAS  Google Scholar 

  33. 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.

    Article  PubMed  CAS  Google Scholar 

  34. Cushman M, Rosendaal FR, Psaty BM, et al.: Factor V Leiden is not a risk factor for arterial vascular disease in the elderly: results from the Cardiovascular Health Study. Thromb Haemost 1998, 79:912–915.

    PubMed  CAS  Google Scholar 

  35. Broze GJ Jr: Protein Z-dependent regulation of coagulation. Thromb Haemost 2001, 86:8–13.

    PubMed  CAS  Google Scholar 

  36. Vasse M, Guegan-Massardier E, Borg JY, et al.: Frequency of protein Z deficiency in patients with ischaemic stroke. Lancet 2001, 357:933–934.

    Article  PubMed  CAS  Google Scholar 

  37. Lopaciuk S, Bykowska K, Kwiecinski H, et al.: Protein Z in young survivors of ischemic stroke. Thromb Haemost 2002, 88:536.

    PubMed  CAS  Google Scholar 

  38. 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.

    PubMed  CAS  Google Scholar 

  39. Ridker PM, Hennekens CH, Miletich JP: G20210A mutation in prothrombin gene and risk of myocardial infarction, stroke, and venous thrombosis in a large cohort of US men. Circulation 1999, 99:999–1004.

    PubMed  CAS  Google Scholar 

  40. Smiles AM, Jenny NS, Tang Z, et al.: 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.

    PubMed  CAS  Google Scholar 

  41. Bajzar L: Thrombin activatable fibrinolysis inhibitor and an antifibrinolytic pathway. Arterioscler Thromb Vasc Biol 2000, 20:2511–2518.

    PubMed  CAS  Google Scholar 

  42. Santamaria A, Oliver A, Borrell M, et al.: Risk of ischemic stroke associated with functional thromb-inactivatable fibrinolysis inhibitor plasma levels. Stroke 2003, 34:2387–2391.

    Article  PubMed  CAS  Google Scholar 

  43. van Goor ML, Garcia EG, Leebeek F, et al.: The plasminogen activator inhibitor (PAI-1) 4G/5G promoter polymorphism and PAI-1 levels in ischemic stroke. A case-control study. Thromb Haemost 2005, 93:92–96.

    PubMed  Google Scholar 

  44. Bang CO, Park HK, Ahn MY, et al.: 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene and insertion/deletion polymorphism of the tissue-type plasminogen activator gene in atherothrombotic stroke. Cerebrovasc Dis 2001, 11:294–299.

    Article  PubMed  CAS  Google Scholar 

  45. Wiklund PG, Nilsson L, Ardnor SN, et al.: Plasminogen activator inhibitor-1 4G/5G polymorphism and risk of stroke: replicated findings in two nested case-control studies based on independent cohorts. Stroke 2005, 36:1661–1665.

    Article  PubMed  CAS  Google Scholar 

  46. Catto AJ, Carter AM, Stickland M, et al.: Plasminogen activator inhibitor-1 (PAI-1) 4G/5G promoter polymorphism and levels in subjects with cerebrovascular disease. Thromb Haemost 1997, 77:730–734.

    PubMed  CAS  Google Scholar 

  47. Boers GH: Hyperhomocysteinemia as a risk factor for arterial and venous disease. A review of evidence and relevance. Thromb Haemost 1997, 78:520–522.

    PubMed  CAS  Google Scholar 

  48. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG: A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA 1995, 274:1049–1057.

    Article  PubMed  CAS  Google Scholar 

  49. Moster ML: Coagulopathies and arterial stroke. J Neuroophthalmol 2003, 23:63–71.

    PubMed  Google Scholar 

  50. 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 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kenneth K. Wu MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Matijevic, N., Wu, K.K. Hypercoagulable states and strokes. Curr Atheroscler Rep 8, 324–329 (2006). https://doi.org/10.1007/s11883-006-0011-2

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11883-006-0011-2

Keywords

Navigation