Short-term venous stasis induces fibrinolytic activation but not thrombin formation.

Abstract

Venous stasis is a well-known risk factor for the development of venous thromboembolism. It is likely that stasis increases the risk of thrombosis by inducing hypercoagulability via the hypoxic procoagulant activation of endothelial and mononuclear cells and the accumulation of activated clotting factors. However, increased rates of thrombin formation have not been demonstrated in response to venous stasis in vivo. In this study, we used the venous occlusion (VO) test to determine, if stasis triggers thrombin formation in healthy individuals (n=25) and patients with additional thrombotic risk factors, such as inherited thrombophilia (n=19) and symptomatic atherosclerosis (n=15). Thrombin formation was monitored by measuring plasma levels of free thrombin using a highly sensitive oligonucleotide enzyme capture assay (OECA) in addition to the plasma levels of prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin-complexes (TAT). The plasma levels of activated protein C (APC) were additionally measured using an APC-OECA. VO induced a significant (p<0.05) increase in the levels of tissue-type plasminogen activator and plasmin-α2-antiplasmin-complexes. In all three cohorts, the majority of samples obtained during VO showed no quantifiable thrombin or APC levels. Consistent with these findings F1+2 and TAT did not change. We conclude that short-term venous stasis induces a profibrinolytic response due to the activation of endothelial cells, but not a prothrombotic response, even in the presence of additional thrombophilic risk factors. Furthermore, our results support the hypothesis that the stasis-induced profibrinolytic activation of endothelial cells occurs independently from thrombin formation.