Non-Responders Following Venous Occlusion

Lacroix, Karol

Abstract

. The purpose of this project is to: (1) identify a population of non-responders and (2) to determine if there is any abnormality which can be detected with selected clinical assays in the activation or inhibition of fibrinolysis within this group. Non-responders are individuals who have normal fibrinolytic activity at rest but do not demonstrate the expected in vitro increase following the application of stressors such as venous occlusion or acute exercise. In this proposed study, fasting venous blood samples will be drawn pre- and post-venous occlusion from 200 volunteers between the ages of 18 and 25 years and screened for fibrinolytic activity using the fibrin plate assay. Those subjects who demonstrate an increased fibrinolysis following venous occlusion will be termed responders and those who do not will be classified as non-responders. Plasma from both groups will be analyzed for factors associated with the activation or inhibition of fibrinolysis including free and total tissue plasminogen activator (t-PA), PAI-1 which is the major inhibitor to t-PA, Protein C antigen and activity levels, kallikrein, Factor XII, plasminogen, alpha-2 antiplasmin, serum lipids, lipoproteins, and apolipoproteins. Thrombosis occurs when there is an imbalance in the hemostatic mechanism. It is associated with excessive or uncontrolled clotting, decreased levels of naturally occurring inhibitors such as antithrombin III and Protein C, or hypofibrinolysis. This study will determine if healthy non-responders have a detectable abnormality associated with the activation or inhibition of fibrinolysis following the application of a stressor, and may represent a means to screen individuals who could be at risk for thrombotic. It also provides the impetus for future studies on family members of nonresponders to determine if they have the same diminished fibrinolytic response following venous occlusion or have experienced thrombotic complications. Lastly, this study will provide valuable specimens for additional hemostasis determinations in other laboratories.