T hrombophilia: A Mechanism of Disease in Women With Adverse Pregnancy Outcome and T hrombotic Lesions in the Placenta Fernando Arias, MD, PhD, 1 * Roberto Romero, MD, 2,3 Heinrich Joist, MD, PhD, 4 and Frederick T. Kraus, MD 1 1 Departments of Obstetrics and Gynecology and Laboratory Medicine, St. John’s Mercy Medical Center, St. Louis, Missouri 2 Department of Obstetrics and Gynecology, Wayne State University/ Hutzel Hospital, Detroit, Michigan 3 Perinatology Research Branch, NICHD, Detroit, Michigan 4 Hemostasis and Thrombosis Unit, St. Louis University Health Sciences Center, St. Louis, Missouri Abstract The purpose of this study was to examine the relationship among adverse pregnancy outcome, the presence of thrombotic lesions in the placenta, and the frequency and type of laboratory abnormalities consistent with the presence of a thrombophilic state. A retrospective cohort study was designed to determine the frequency of laboratory abnormalities consistent with thrombophilia among patients with thrombotic lesions of the placenta and adverse pregnancy outcome. The workup for a thrombophilic state included anticardiolipin antibodies, lupus anticoagulant, protein C and antithrombin III activities, protein S total and free, activated protein C resistance ratio, and Factor V Leiden mutation. Thrombotic lesions were identified by histopathologic examination of the placenta. Thirteen patients met the study criteria over an 11-month period. Seven patients were heterozygous for Factor V Leiden mutation (53.8%). Protein S deficiency was found in three cases (23.0%), and no hemostatic abnormality was detected in three cases (23.0%). Mothers with an adverse pregnancy outcome and thrombotic lesions of the placenta often have laboratory abnormalities indicative of a thrombophilic state. We propose that thrombophilia leading to thrombosis in the maternal and/or fetal circulations is a significant mechanism of disease during pregnancy. J. Matern.–Fetal Med. 7:277–286, 1998.  1998 Wiley-Liss, Inc. Key words: thrombophilia; placental thrombosis; adverse pregnancy outcome IN TRO DUCTIO N A solid body of evidence indicates that activation of the hemostatic system is an important mechanism of human disease. A hypercoagulable state has long been implicated in the pathogenesis of coronary artery disease [1], stroke [2], deep vein thrombosis [3], pulmonary emboli [4], and vascu- lar complications of diabetes mellitus [5]. Recently, exces- sive hemostasis also has been shown to play a role in some of the complications associated with paroxysmal nocturnal hemoglobinuria [6], sickle cell disease [7], thalassemia [8], and spinal cord injuries [9]. Pregnancy is a hypercoagulable state, and thrombotic lesions in the placenta are a common finding in major complications of pregnancy such as preeclampsia [10], stillbirth [11,12], fetal growth retardation [13,14], preterm labor [15], and preterm rupture of membranes [16]. Yet, in most cases a definitive link among adverse pregnancy outcome, thrombotic lesions of the placenta, and a specific thrombophilic condition isnot recognized. Recently, signifi- cant progress has been made in the laboratory identification of congenital and acquired disorders that are responsible for thrombophilic states in the nonpregnant individual. Placentation imposes considerable demands on the circu- latory and homeostatic systems. Trophoblast invasion of the maternal circulation, maintenance of blood fluidity in the intervillous space, and separation of the placenta after delivery all require a fine balance between prothrombotic *Correspondence to: Fernando Arias, M.D., St. John’s Mercy Medical Center, St. Louis, MO 63141. Received 26 May 1998; revised 18 June 1998; accepted 20 June 1998 The Journal of Maternal-Fetal Medicine 7:277–286 (1998)  1998 Wiley-Liss, Inc.