Loading

wait a moment

Thrombin, Inflammation, and Cardiovascular Disease: Thrombotic disease

Overall, a meta-analysis demonstrated moderate risk prediction for d-dimer. The most likely interpretation of these data are that the degree of atherosclerosis and vascular damage causes changes in coagulation status, not vice versa; ie, it does not appear that a preexisting hypercoag-ulable state is in the causal pathway of atherosclerotic disease and CVD events. This position is supported by the findings such as those of Lowe et al, in which future ischemic events were predicted by d-dimer levels but not by other markers of procoagulant activity, such as prothrombin fragment F1 + 2 and thrombin-antithrombin complex (measures of thrombin generation), or by factor VII coagulant activity (factor VIIc, which at least partly reflects factor VII activation). Link
Genetic studies also provide some information regarding the possible role of hypercoagulability in precipitating CVD events. For example, there are unambiguous and compelling associations between genetic protein C deficiency (lack of an anticoagulant), factor V Leiden genotype (a procoagulant resistant to inactivation), and prothrombin 20210A genotype (increased procoagulant zymogen levels), and the prevalence and incidence of venous thrombotic disease. The general statement is that the presence of genetic factors that result in either reduced anticoagulation or increased procoagulation are directly in the causal pathway for venous thrombosis. However, key to our interpretation of hypercoagulability, in general none of these factors are risk factors for arterial disease. There are rare exceptions, such as atypical arterial thrombosis occurring in otherwise healthy younger women. Overall, the preponderance of data indicates a lack of a compelling argument supporting the importance of a preexisting hypercoagulable state as a major risk factor for athero-thrombotic disease.