Mechanism
Thrombosis is a multifactorial problem because there are often multiple reasons why a person might develop thrombosis. These risk factors may include any combination of abnormalities in the blood vessel wall, abnormalities in the blood flow (as in immobilization), and abnormalities in the consistency of the blood. Thrombophilia is caused by abnormalities in blood consistency, which is determined by the levels of coagulation factors and other circulating blood proteins that participate in the "coagulation cascade".
Normal coagulation is initiated by the release of tissue factor from damaged tissue. Tissue factor binds to circulating factor VIIa. The combination activates factor X to factor Xa and factor IX to factor IXa. Factor Xa (in the presence of factor V) activates prothrombin into thrombin. Thrombin is a central enzyme in the coagulation process: it generates fibrin from fibrinogen, and activates a number of other enzymes and cofactors (factor XIII, factor XI, factor V and factor VIII, TAFI) that enhance the fibrin clot. The process is inhibited by TFPI (which inactivates the first step catalyzed by factor VIIa/tissue factor), antithrombin (which inactivates thrombin, factor IXa, Xa and XIa), protein C (which inhibits factors Va and VIIIa in the presence of protein S), and protein Z (which inhibits factor Xa).
In thrombophilia, the balance between "procoagulant" and "anticoagulant" activity is disturbed. The severity of the imbalance determines the likelihood that someone develops thrombosis. Even small perturbances of proteins, such as the reduction of antithrombin to only 70–80% of the normal level, can increase the thrombosis risk; this is in contrast with hemophilia, which only arises if levels of coagulation factors are markedly decreased.
In addition to its effects on thrombosis, hypercoagulable states may accelerate the development of atherosclerosis, the arterial disease that underlies myocardial infarction and other forms of cardiovascular disease.
Read more about this topic: Thrombophilia
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