Baseline fibrinolytic state and the risk of future venous thrombosis: A prospective study of endogenous tissue-type plasminogen activator and plasminogen activator inhibitor

Background. Although isolated abnormalities of plasminogen activation and inhibition have been reported among selected patients with venous thrombosis, it is unclear whether these deficiencies of fibrinolysis are important risk factors for thromboembolic disease. Methods and Results. To evaluate whether baseline levels of endogenous tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) predict the future occurrence of venous thrombosis, levels of these proteins were measured in prospectively collected plasma samples from 55 participants in the Physicians' Health Study who later developed deep venous thrombosis or pulmonary embolism and from an equal number of age- and smoking-matched control subjects who remained free of vascular disease during a mean follow-up period of 60.2 months. Overall, there were no statistically significant differences between case patients and control subjects in baseline levels of PAI-1 (50.5 versus 59.5 ng/ml, p=0.26), t-PA (13.4 versus 13.3 ng/ml, p=0.94), or PAI-1:t-PA ratio (6.84 versus 6.58, p=0.82). No evidence of a threshold effect or trend was seen when these data were analyzed by increasing quartiles of PAI-1 (p=0.73), t-PA (p=0.62), or PAI-1:t-PA ratio (p=0.93). These results were unchanged after multivariate analysis that simultaneously controlled for other baseline cardiovascular risk factors. Conclusions. In contrast to previous uncontrolled case series and smaller retrospective studies, these prospective data provide strong evidence that baseline fibrinolytic state, as measured by t-PA and PAI-1, does not predict the occurrence of future venous thrombosis.