Thrombophilia: An Update

Abstract

This issue of Seminars in Thrombosis and Hemostasis is dedicated to inherited thrombophilia. The various clinical manifestations and implications for testing are discussed in different articles. Furthermore, animal models that are being used to study thrombophilia are discussed. Thrombophilia is defined as a disorder associated with an increased tendency to venous thromboembolism (VTE). Thrombophilia can be acquired (such as in patients with cancer) or congenital, in which case a defect in the coagulation system is inherited. The term thrombophilia was introduced as aMeSH (Medical Subject Headings) term in 1998, and using this as a search term in the PubMed database at present yields more than 16,500 publications, of which the vast majority is related to inherited forms of this condition. This introduction provides a short overview of thrombophilia, with an emphasis on topics that will not be covered in the reviews in this issue. The first case of inherited thrombophilia was described in 1965 by Egeberg in a publication on a Norwegian family with a remarkable tendency to develop venous thrombosis, which was shown to be due to a deficiency of the physiologic anticoagulant antithrombin. Since then, various forms of inherited thrombophilia have been identified and in a large number of clinical studies, the relative and absolute risk for VTE of each of these thrombophilic conditions has been studied. It is important to emphasize that thrombophilia is diagnosed on clinical grounds. Major criteria are listed in Table 1. The most common features are recurrent VTE, a family history of thrombosis, thrombosis at an unusual location, and thrombosis at young age, but it should be realized that the majority of patients with thrombophilia will have their first manifestation of thrombosis at a later age. In most patients with inherited thrombophilia, the tendency to VTE is mild to moderate and can be controlled easily with antithrombotic agents. Defects leading to inherited thrombophilia may also cause clinical manifestations other than thrombosis, such as skin necrosis in patients with a protein C deficiency who are treated with vitamin K antagonists, or neonatal purpura fulminans in homozygous protein C deficiency (Fig. 1). In addition, many thrombophilic disorders are associated with an increased risk of pregnancy loss, preeclampsia, and the hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome of pregnancy.