Impaired factor XIIa–dependent activation of fibrinolysis in treated antiphospholipid syndrome gestations developing late-pregnancy complications Francisco Carmona, MD, a Isabel La ´zaro, MD, a Juan C. Reverter, MD, b Dolors Ta `ssies, MD, b Josep Font, MD, c Ricard Cervera, MD, c Juan Balasch, MD a, * Institut Clı´nic of Gynecology, Obstetrics, and Neonatology, a Hemotherapy and Hemostasis Unit, b and Department of Autoimmune Diseases, c Faculty of Medicine–University of Barcelona, Hospital Clı´nic-Institut d’Investigacions Biome`diques August Pi I Sunyer, Barcelona, Spain Received for publication May 12, 2005; revised August 2, 2005; accepted August 22, 2005 KEY WORDS Antiphospholipid syndrome Factor XII activity Fibrinolysis Hemostasis Pregnancy complications Objective: The objective of the study was to investigate the potential role of impaired factor XII– dependent activation of fibrinolysis in treated antiphospholipid syndrome gestations developing late-pregnancy complications. Study design: This was a prospective study in a third-level teaching hospital, including 75 pa- tients: 25 pregnant patients having the antiphospholipid syndrome and carrying their pregnancies until 26 weeks’ gestation or later (group 1); 25 pregnant patients having normal term pregnancies and delivery and no previous miscarriage (group 2); and 25 pregnant patients being diagnosed as having severe pre-eclampsia and/or intrauterine growth restriction but testing negative for anti- phospholipid antibodies (group 3). Hemostatic evaluation was carried out from patients in groups 1 and 2 between 6 and 10 weeks, between 18 and 22 weeks, and between 28 and 32 weeks’ ges- tation. Patients in group 3 were sampled between 28 and 32 weeks. An additional blood sample was obtained 4 to 6 months after delivery (baseline). The Mann-Whitney U test, the Friedman test, and the c 2 test were used. Results: Patients in group 1 were characterized by increased factor VIIa levels, increased pro- thrombin fragment 1C2 levels, reduced factor XIIa levels, diminished functional urokinase-type plasminogen activator levels, and decreased levels of plasmin/alpha-2-plasmin inhibitor com- plexes. These abnormalities were more evident in patients in group 1 developing pre-eclampsia and/or intrauterine growth restriction. Conclusions: Impaired factor XIIa–dependent activation of fibrinolysis seems to be a key mech- anism related to late-pregnancy complications in patients with the antiphospholipid syndrome. Ó 2006 Mosby, Inc. All rights reserved. Supported in part by by grants from the Instituto de Salud Carlos III (RCMN C03/08), the Comissionat per a Universitat i Recerca-Generalitat de Catalunya (2001SGR 00372), and FIS 02/0696 and FIS 02/0711 from the Fondo de Investigaciones Sanitarias. I.L. was recipient of a grant from the Hospital Clı´nic of Barcelona. * Reprint requests: Juan Balasch, MD, Institut Clı´nic of Gynecology and Obstetrics, Hospital Clı´nic, c/Casanova 143, 08036-Barcelona, Spain. E-mail: jbalasch@ub.edu 0002-9378/$ - see front matter Ó 2006 Mosby, Inc. All rights reserved. doi:10.1016/j.ajog.2005.08.059 American Journal of Obstetrics and Gynecology (2006) 194, 457–65 www.ajog.org