Prothrombotic states in ischemic stroke

Abstract

Ischemic stroke is a complex disease process consisting of multiple underlying mechanisms, including thromboembolic consequences of large arterial atherosclerotic disease. In addition to the traditional stroke risk factors, attention has also been focused on complex hemostatic functions, such as platelet aggregation, thrombin generation, and fibrinolysis. Information from prospective epidemilogic studies of hemostatic risk factors and ischemic stroke is incomplete and sometimes contradictory. There are fairly good data supporting an association between elevated fibrinogen and tissue plasminogen activator antigen and ischemic stroke. However, it is unknown if they are merely epiphenomena or pathogenic. The classic inherited risk factors for venous thromboembolic events (ie, antithrombin, protein C, and protein S deficiencies, and factor V Leiden and prothrombin G20210A polymorphisms) do not appear to be strong, independent risk factors in unselected stroke patients. Discovery of genetic polymorphisms in many hemostatic genes has stimulated searches for gene-disease associations, frequently before establishing that a polymorphism has an effect on protein expression or function. Future investigations into ischemic stroke risk factors should be prospective, enroll much larger numbers of subjects, rigorously classify strokes by subtype, and incorporate evolving molecular techniques to maximize collection of genetic information. This may lead to identification of unique gene-gene and gene-environmental interactions that may improve our understanding of the causes of ischemic strokes.