The role of procoagulants and anticoagulants in the development of venous thromboembolism.

Procoagulant and anticoagulant reactions play an important role in the regulation of thrombin formation during secondary hemostasis. Three phases can be recognized in the kinetics of thrombin formation: an initiation phase, a propagation phase and a termination phase. Dysregulation of thrombin formation during each of these phases by (hereditary) changes in the plasma concentration of pro- and anticoagulants contributes to the development of venous thrombosis. Most important seems the defective down-regulation of the prothrombinase activity during the termination phase. Procoagulant and anticoagulant proteins have important roles in the regulation of fibrin formation during secondary hemostasis. Under normal physiological conditions there is a delicate balance between the procoagulant and anticoagulant reactions. After damage to the vessel wall sufficient fibrin is formed to arrest bleeding and allow repair of the lesion without obstructing blood circulation. Venous thrombosis can be considered as a hemostatic process getting out of control, where massive fibrin formation has resulted in the formation of an obstructive thrombus. Such thrombus formation is believed to be facilitated by changes in the vessel wall, blood flow and the composition of the blood. During the past 50 years substantial progress has been made in our understanding of the enzymatic reactions involved in the hemostatic process. At the same time information has been obtained on particular changes in the composition of the blood which contribute to the development of venous thrombosis. Most of these changes concern the procoagulant and anticoagulant systems. In this paper I will briefly discuss how fibrin formation is regulated by procoagulant and anticoagulant reactions and how certain changes in these pathways contribute to the development of venous thrombosis.