thrombophilias

Thrombophilias are a group of disorders that predispose individuals to thrombosis due to inherited or acquired abnormalities of the coagulation system. They primarily increase the risk of venous thromboembolism, including deep vein thrombosis and pulmonary embolism, and can also contribute to arterial events in some contexts.

Inherited thrombophilias include deficiencies of natural anticoagulants such as antithrombin, protein C, and protein S, as well as common genetic variants like factor V Leiden (activated protein C resistance) and the prothrombin G20210A mutation. Acquired thrombophilias include antiphospholipid syndrome, characterized by antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-beta2-glycoprotein I), and cancer-associated thrombophilia. Other risks that interact with thrombophilia include estrogen-containing medications, pregnancy, obesity, surgery, immobilization, and inflammatory states.

The underlying mechanism involves an imbalance between procoagulant and anticoagulant forces, leading to a hypercoagulable state. This predisposes to clot formation under various circumstances, with recurrent events more likely in some individuals and contexts.

Clinical presentation depends on the site of thrombosis. Most events are venous, such as leg DVT or PE; antiphospholipid syndrome can also cause miscarriages and arterial thrombosis in some patients. Family history and personal history of VTE influence the likelihood of testing.

Diagnosis is guided by clinical context. Genetic testing for inherited thrombophilias is often reserved for younger patients with unprovoked VTE or special circumstances, while antiphospholipid antibodies require specific assays (lupus anticoagulant, anticardiolipin, anti-beta2-glycoprotein I) with repeat testing after several weeks. Anticoagulation decisions depend on the individual risk profile and event history.

Management focuses on risk factor modification and anticoagulation for acute events. Long-term anticoagulation may be considered after unprovoked or recurrent VTE or in high-risk antiphospholipid syndrome. In pregnancy, low-molecular-weight heparin is commonly used; direct oral anticoagulants are used selectively, with attention to guidelines for particular conditions.