or in the period after surgery. Various coagulation abnormalities have been described in the obese. Plasminogen activator inhibitor-1, an inhibitor of fibrinolysis, is present in higher levels in people with obesity. Obese people also have larger numbers of circulating microvesicles (fragments of damaged cells) that bear tissue factor. Platelet aggregation may be increased, and there are higher levels of coagulation proteins such as von Willebrand factor, fibrinogen, factor VII and factor VIII. Obesity also increases the risk of recurrence after an initial episode of thrombosis. Unclear A number of conditions that have been linked with venous thrombosis are possibly genetic and possibly acquired. These include: elevated levels of factor VIII, factor IX, factor XI, fibrinogen and thrombin-activatable fibrinolysis inhibitor, and decreased levels of tissue factor pathway inhibitor. Activated protein C resistance that is not attributable to factor V mutations is probably caused by other factors and remains a risk factor for thrombosis. There is an association between the blood levels of homocysteine and thrombosis, although this has not been reported consistently in all studies. Homocysteine levels are determined by mutations in the MTHFR and CBS genes, but also by levels of folic acid, vitamin B6 and vitamin B12, which depend on diet. 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