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Management of inherited thrombophilia

INTRODUCTION

Inherited thrombophilia is a genetic tendency to venous thromboembolism. Factor V Leiden is the most common cause of the syndrome, accounting for 40 to 50 percent of cases. The prothrombin gene mutation, deficiencies in protein S, protein C, and antithrombin account for most of the remaining cases, while rare causes include the dysfibrinogenemias [1]. The total incidence of an inherited thrombophilia in subjects with a deep vein thrombosis ranges from 24 to 37 percent overall compared with about 10 percent in controls. (See "Overview of the causes of venous thrombosis", section on 'Inherited thrombophilia'.)

Management issues related to thromboembolism in patients with inherited thrombophilia are reviewed here [2]. The initial management of acute thromboembolic disease in patients with inherited risk factors for thrombosis is not different from that in other patients. Less well established is the long-term management of patients with inherited thrombophilia who have had venous thrombosis and of patients exposed to the increased risk associated with pregnancy and surgery. In most cases, randomized prospective studies have not been performed, and only general guidelines are available for the clinician taking care of these patients.

The usefulness of screening for these conditions in various asymptomatic populations and the value of screening in patients presenting with thrombosis are discussed separately. (See "Screening for inherited thrombophilia in asymptomatic populations" and "Evaluation of the patient with established venous thrombosis", section on 'Screening for Inherited thrombophilia'.) Issues related to the management of pregnant women with inherited thrombophilia are discussed separately. (See "Inherited thrombophilias in pregnancy" and "Anticoagulation during pregnancy" and "Deep vein thrombosis and pulmonary embolism in pregnancy: Epidemiology, pathogenesis, and diagnosis" and "Deep vein thrombosis and pulmonary embolism in pregnancy: Prevention".) and (see "Deep vein thrombosis and pulmonary embolism in pregnancy: Treatment".

INITIAL TREATMENT OF ACUTE VENOUS THROMBOEMBOLISM

The usual initial treatment of acute venous thromboembolism consists of unfractionated heparin or low-molecular-weight heparin followed by anticoagulation with warfarin for 3 to 12 months. Warfarin can be started within the first 24 hours. Heparin or low-molecular-weight heparin is continued for at least five days and until the prothrombin time has been in the therapeutic range (ie, INR of 2.0 to 3.0) for at least two days. (See "Treatment of deep vein thrombosis", section on 'Initial anticoagulation regimen' and "Treatment of acute pulmonary embolism".)

During this initial period of anticoagulation, special consideration may need to be given to selected patients known to have hereditary antithrombin or protein C deficiency, as discussed below. Routine measurement of plasma antithrombin or protein C concentrations in all individuals presenting with thrombosis is not recommended.
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