Heritable and Acquired Thrombophilias in Clinical Practice

Thrombosis is common in clinical practice. Venous thromboembolism in particular raises questions of a possible underlying hereditary or acquired thrombophilic state. Despite considerable data describing the impact of various thrombophilic states on risks of initial and recurrent thromboembolic events, thrombophilia testing is not standardized. An understanding of the utility and pitfalls of clinical thrombophilia testing is necessary to employ this testing properly. When utilized appropriately, thrombophilia testing can be vital in informing an individual patient’s thrombosis risk and pursuing optimal anticoagulant management. Hereditary thrombophilia testing involves investigation for factor V Leiden, the prothrombin G202010A gene mutation, and deficiencies of the natural anticoagulants protein C, protein S, and antithrombin. Assessment for acquired thrombophilias is perhaps even more important, recognizing the possibility for myeloproliferative neoplasms, antiphospholipid antibody syndrome, occult malignancy and other important acquired thrombotic predispositions. Timing of thrombophilia testing in relation to anticoagulation, acute thrombosis, and use of hormonal agents or pregnancy is critical to ensure accurate diagnosis. This review describes each of the most important hereditary and acquired thrombophilias, explains their relationship to venous and arterial thrombosis, delineates evidence-based indications for thrombophilia testing, identifies potential testing pitfalls, and synthesizes the key points in outlining algorithms for thrombophilia testing in clinical practice. This review contains 4 figures, 4 tables, and 48 references. Key words: thrombophilia, venous thromboembolism, pulmonary embolus, deep vein thrombosis, factor V Leiden, prothrombin gene mutation, protein C deficiency, protein S deficiency, antiphospholipid antibody syndrome, hypercoagulability of malignancy