In those with unprovoked and/or recurrent thrombosis, or those with a high-risk form of thrombophilia, the most important decision is whether to use anticoagulation medications, such as warfarin, on a long-term basis to reduce the risk of further episodes. This risk needs to weighed against the risk that the treatment will cause significant bleeding, as the reported risk of major bleeding is over 3% per year, and 11% of those with major bleeding may die as a result.Apart from the abovementioned forms of thrombophilia, the risk of recurrence after an episode of thrombosis is determined by factors such as the extent and severity of the original thrombosis, whether it was provoked (such as by immobilization or pregnancy), the number of previous thrombotic events, male sex, the presence of an inferior vena cava filter, the presence of cancer, symptoms of post-thrombotic syndrome, and obesity. These factors tend to be more important in the decision than the presence or absence of a detectable thrombophilia.Those with antiphospholipid syndrome may be offered long-term anticoagulation after a first unprovoked episode of thrombosis. The risk is determined by the subtype of antibody detected, by the antibody titer (amount of antibodies), whether multiple antibodies are detected, and whether it is detected repeatedly or only on a single occasion.Women with a thrombophilia who are contemplating pregnancy or are pregnant usually require alternatives to warfarin during pregnancy, especially in the first 13 weeks, when it may produce abnormalities in the unborn child.
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.