Fifty percent of the patients with thrombosis during pregnancy will be found to have an underlying thrombophilia. == 2. women with thrombophilias and pregnancy-associated thrombosis may help clarify the management CGP 65015 of this condition in the future. == 1. Introduction == The risk of venous thromboembolic events (VTE) is high during pregnancy due to both physiologic changes of pregnancy and the additional impact CGP 65015 of the inherited and acquired thrombophilias. The overall rate of venous thromboembolic events in pregnancy is 200 per 100,000 deliveries [1]. The main risk appears to occur in the postpartum period where the incidence increases almost 2.5-fold and is estimated at 500 per 100,000. The majority of these events are deep vein thrombosis as opposed to the more deadly pulmonary embolism. Venous thromboembolic events remain a leading cause of death which has been estimated to range from 1.2 to 4.7 per 100,000 pregnancies. Inherited and acquired thrombophilias contribute further to an increased predisposition to thrombotic events. The overall impact of the inherited and acquired thrombophilias is low in the nonpregnant population, and the majority of patients never experience a thrombotic event. During pregnancy, however, the increased risk of thromboses in patients with inherited and acquired thrombophilias can be substantial and warrants consideration, especially as thrombosis is the leading cause of mortality during pregnancy. Fifty percent of the patients with thrombosis during pregnancy will be found to have an underlying thrombophilia. == 2. Pathophysiologic Changes during Pregnancy == The physiological changes that occur during pregnancy are mainly responsible for the increased thrombogenicity of the peripartum period. A number of clotting factors including factor VII, factor VIII, Factor X, von Willebrand factor, and fibrinogen are elevated as a result of hormonal changes. At the same time, resistance to activated protein C increases in the second and third trimesters and the activity of protein S is decreased due to changes in the total protein S antigen level [2]. There is also an increase in a number of inhibitors of the fibrinolytic pathway such as activatable fibrinolytic inhibitor (TAFI) and plasminogen activator inhibitor 1 and 2 (PAI-1 and PAI-2) [3,4]. In addition, the physical changes of pregnancy result in an increased thrombotic state. Increased pressure on the pelvic veins from the gravid uterus and decreased flow in the lower extremities result in increased stasis. Relative compression of the left iliac vein by the right iliac artery as it courses across the vessel leads to an increase of clots in the left iliac vein [5,6]. Although stasis increases throughout the course of pregnancy and leg pain and swelling are more frequent during the third trimester, incidence of DVT is distributed relatively equally across trimesters [7]. Concomitant diseases such as MGC24983 systemic lupus erythematous or sickle cell disease as well as other risk CGP 65015 factors including obesity, decreased mobility, increased age, and smoking all increase the risk of thrombosis. It has been estimated that the women who are over 35 and pregnant have a 1.38-fold increased risk of having a clotting event during CGP 65015 the peripartum period [8]. Women who have had spontaneous clotting events in the past have an increased risk of developing a second event with an estimated rate of recurrence of 10.9% during pregnancy [9]. Overall, both the physiologic and anatomic changes of pregnancy take several weeks to resolve after delivery, and the risk of thrombosis remains elevated (and indeed even elevated compared to pregnancy) until approximately 6 weeks postpartum [1]. == 3. CGP 65015 Acquired and Inherited Thrombophilias == == 3.1. Acquired Disorders == The main acquired thrombophilia leading to increased risk of VTE in pregnancy is the antiphospholipid antibody syndrome. A number of criteria must be met in order to make a diagnosis of antiphospholipid antibody syndrome. This includes one or more episodes of document thrombosis, and/or recurrent (3 or more) early miscarriages occurring in the first 10 weeks of gestation, 1 or more fetal losses occurring after 10 weeks or preterm delivery at 34 weeks for preeclampsia or placental insufficiency. These clinical scenarios must also be accompanied by defined laboratory criteria. Lupus anticoagulant (LAC) must be present in the plasma on 2 separate occasions at least 12 weeks apart and/or anticardiolipin (aCL) antibody of either the IgG or IgM isotype (or both) present in plasma at medium to high titers (>40), or the presence of anti-beta2-glycoprotein (anti-b2GPI) of IgG or IgM isotype must be present on 2 or more occasions again at least 12 weeks apart [10]. Antiphospholipid antibody syndrome has been associated with an odds ratio of 15.8 for clotting risk.