Understanding of Coagulation/Fibrinolysis Mechanism Leads to the Cure and Prevention of Thrombosis
 In the middle of the 1800's, Rudolph Virchow described the triad of factors, viz., stasis, changes in the vessel wall, and in the blood, as the causes which could explain the presence of thrombus in the deep vein of the leg. Later, the role and significance of platelets in the initiation and pathogenesis of arterial thrombosis was established.
A thrombus is a blood-derived mass formed on endovascular or endocardial surfaces. It probably represents an excessive response of the hemostasis mechanism to altered vascular surfaces under variable flow conditions. Thrombi may occur anywhere in the circulation, e.g., in arteries, veins, capillaries, or chambers of the heart. Thrombosis plays important roles in the pathogenesis of heart attacks and strokes and are, therefore, significant causes of morbidity and mortality in Western society.
In vitro, fibrin formation is considered a prerequisite for the activation of the fibrinolytic system and the generation of crosslinked (XL)-fibrin degradation products (FDPs). Thus, D-dimer is regarded as the product of downstream events after the initiation of the coagulation and fibrinolytic system, while fibrin monomers are produced at the initial stage of fibrinogen-fibrin transition after the removal of fibrinopeptide A (FPA). Subsequently, fibrin monomers polymerize to form fibrin polymers whose conformation facilitates the release of fibrinopeptide B (FPB) by thrombin. In the presence of excess fibrinogen in plasma, the fibrin polymers form soluble complexes with fibrinogen molecules. The complexes are generally referred to as “soluble fibrin” (SF).
Setting aside for the time being, the essential role played by platelets in thrombogenesis, the intermediates of fibrinogen-fibrin transition, biz. Soluble fibrin and D-dimer, could be quite useful in predicting the development of acute hypercoagulable state which might lead to deep vein thrombosis, pulmonary embolism or acute respiratory distress syndrome. We have been assaying these two parameters of fibrinogen-fibrin transition in trauma patients, transplant patients and obstetric patients with pregnancy problems. Also, we have been measuring thrombin activatable fibrinolysis inhibitor (TAFI) and plasminogen activator inhibitor-1 (PAI-1) in patients under hormone replacement therapy.
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