Reduced Plasma Fibrinolytic Potential Is a Risk Factor for Venous Thrombosis.

Abstract

The role of the fibrinolytic system in the development of deep vein thrombosis (DVT) is unclear. We determined the plasma fibrinolytic potential of patients enrolled in the Leiden Thrombophilia Study (LETS), a population-based case-control study on risk factors for DVT. Plasma fibrinolytic potential was determined in 421 patients and 469 controls who were not using oral anticoagulants at the time of the blood draw by means of a tissue factor- and tissue-type plasminogen activator (tPA)-induced clot lysis assay. This assay represents an overall measure for plasma fibrinolytic potential, as it was previously shown to be dependent on plasma levels of plasminogen, α2-antiplasmin, plasminogen activator inhibitor type 1, and thrombin activatable fibrinolysis inhibitor. Using clot lysis times above the 70th, 80th, 90th, 95th, and 99th percentile of the values found in control subjects as cut-off levels, we found a dose-dependent increase in risk for DVT in patients with hypofibrinolysis (odds ratio’s [95 % CI] of 1.4 [1.1–1.8], 1.6 [1.2–2.1], 1.9 [1.3–2.9], 2.1 [1.3–3.6], 2.2 [0.7–7.5], respectively). This indicates a two-fold increased risk of DVT in subjects with clot lysis times above the 90th percentile. Using the 90th percentile, we showed that the risk was not affected by age or sex (odds ratio [95% CI] 2.0 [1.3–3.0]), and after correction for all possible confounders (age, sex, and levels of procoagulant proteins which were shown to associate with clot lysis times in the control population) the risk estimate was marginally reduced (odds ratio [95% CI] 1.6 [1.0–2.5]). Taken together, these results indicate that plasma hypofibrinolysis constitutes a risk factor for venous thrombosis. Whether this hypofibrinolytic state is determined by genetic or acquired factors, or a combination of these, and which proteins are involved is at present unknown.