Thrombophilia refers to laboratory abnormalities that increase the risk of venous thromboembolism (VTE). Over the past several decades, numerous factors have been identified. The most prevalent examples of hereditary forms of thrombophilia include the factor V Leiden and prothrombin G20210A mutations; deficiencies of the natural anticoagulants antithrombin, protein C, and protein S; persistently elevated levels of coagulation factor VIII; and mild hyperhomocysteinemia. Taken together, some form of hereditary thrombophilia can be identified in more than 50 percent of patients with VTE who are without obvious reasons for VTE, such as trauma or prolonged stasis. Moreover, hereditary thrombophilia has been associated with arterial cardiovascular disease and obstetric complications such as (recurrent) pregnancy loss and preeclampsia. The high yield of thrombophilia testing has led to widespread testing for these abnormalities in patients. Nevertheless, thrombophilia testing remains a topic of ongoing debate, mostly because of the lack of evidence-based therapeutic consequences. While hereditary thrombophilia is a clear risk factor for a first VTE, the risk for recurrent episodes is only slightly increased compared with nonaffected patients, and prolonged anticoagulation is probably not warranted unless VTE is recurrent. A similar lack of therapeutic consequences applies to patients with arterial cardiovascular disease and women with obstetric complications. Thrombophilia testing in asymptomatic relatives of patients with VTE may be useful in families with antithrombin, protein C, or protein S deficiency, or for siblings of patients who are homozygous for factor V Leiden, and is limited to women who intend to become pregnant or who would like to use oral contraceptives. Careful counseling with knowledge of absolute risks helps patients to make an informed decision in which their own preferences can be taken into account.
To our knowledge, the term thrombophilia was first used by Nygaard and Brown in 1937, when they described sudden occlusion of large arteries, sometimes with coexistent venous thrombosis.1 In 1956, Jordan and Nandorff extensively reviewed their own and previously published cases on the familial tendency in thromboembolic disease.2 The term thrombophilia was then used to describe patients with prominent manifestations of venous thromboembolism (VTE; venous thrombosis in any site or pulmonary embolism) such as recurrent spontaneous VTE, VTE at young age, a strong family history of VTE, or thrombosis in an unusual site, such as the splanchnic veins or cerebral sinuses. Currently, the term thrombophilia is generally used for laboratory abnormalities, usually in the coagulation system, which increase the risk of VTE. Thrombophilia can be either acquired or hereditary. An example of acquired thrombophilia is the antiphospholipid syndrome, which is characterized by a tendency toward venous or arterial thrombosis or pregnancy complications, in combination with persistent lupus anticoagulant or antibodies to cardiolipin or β2-glycoprotein-1 (Chap. 21). Furthermore, there are many acquired and transient conditions that lead to a prothrombotic state, including cancer, surgery, strict immobilization, pregnancy and the postpartum period, and the use of estrogen-containing medication, such as oral contraceptives and hormone replacement therapy.