Semin Reprod Med 2006; 24: 054-066 DOI: 10.1055/s-2006-931801
Copyright © 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.
Thrombophilias and Recurrent Pregnancy Loss
William H. Kutteh1, Douglas A. Triplett2
1 Professor of Obstetrics and Gynecology, Director of Reproductive Endocrinology and Infertility, Director of Reproductive Immunology, University of Tennessee, Memphis, Memphis, Tennessee 2 Professor of Pathology, Director of Midwest Hemostasis and Thrombosis Laboratories, Indiana University School of Medicine, Muncie, Indiana

ABSTRACT

Thrombophilia by definition represents acquired and/or genetic conditions that predispose patients to both venous and arterial thromboembolic events. Thrombosis is the most common cause of death worldwide. On the arterial side, myocardial infarction and stroke result in significant morbidity and mortality. Venous thromboembolic events most commonly involve the deep veins of the lower extremity with potential complications of pulmonary emboli. Pregnancy is a hypercoagulable state, and thromboembolism is the leading cause of antepartum and postpartum maternal mortality. With the description by Dahlback in 1993 of a condition initially labeled activated protein C resistance, significant advances have rapidly followed. Activated protein C resistance was linked to an underlying point mutation resulting in coagulation factor V (factor V Leiden). Recent attention has focused on certain inherited thrombophilic factors that may predispose to arterial and/or venous thromboses and their possible association with pregnancy complications, including early pregnancy loss. These include a group of mostly autosomal dominant, inherited gene mutations leading to a hypercoagulable state, such as factor V Leiden G1691A, factor II or prothrombin G20210A, and hyperhomocysteinemia associated with methylenetetrahydrofolate reductase C677T mutation. In addition, deficiencies in protein S, protein C, and antithrombin can lead to a hypercoagulable state. Although some studies of recurrent pregnancy loss patients with a positive test for an inherited thrombophilia are conflicting, a case-control study of untreated recurrent miscarriage patients who were heterozygous for the factor V Leiden mutation revealed a lower success rate than the controls who had a history of idiopathic recurrent miscarriage. With the identification of genetic risk factors, there has been synergistic amplification of thrombotic risk when one has an abnormal gene (e.g., factor V Leiden) plus environmental issues (e.g., pregnancy). Current understanding indicates that a combination of risk factors, including multiple inherited thrombophilic defects associated with secondary hypercoagulable states, have a particularly strong association with adverse pregnancy outcome.

KEYWORDS

Recurrent pregnancy loss - thrombophilias - coagulation abnormalities - miscarriage - antiphospholipid antibodies