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Thromboembolic disease is a major contributor to both perinatal and maternal morbidity and mortality worldwide, accounting for 14.9% of maternal deaths in 2006, according to the World Health Organization (WHO).1 In developed countries, thromboembolism has risen above hemorrhage and hypertension as the leading cause of maternal mortality.2 Venous thromboembolic diseases (VTE)—such as deep venous thrombosis (DVT), pulmonary embolism (PE), septic pelvic thrombophlebitis (SPT), and ovarian vein thrombosis (OVT)—complicate 0.76 to 1.72 per 1000 pregnancies.3 The cornerstones of VTE management lie in prevention, accurate diagnosis, and prompt treatment. This chapter will review the etiology, diagnosis, treatment, and prevention of VTE.




A detailed discussion of the clotting system, the anticoagulant system, and the fibrinolytic system is beyond the scope of this manual and can be found elsewhere in more comprehensive textbooks. A practical and user-friendly version of the complex regulatory pathways of hemostasis and fibrinolysis is presented in Fig. 7-1.


Hemostatic and fibrinolytic pathways. The primary initiator of coagulation is tissue factor (TF) which is not normally expressed by cells in contact with the circulation (ie, endothelial cells). Following vascular disruption, perivascular, cell membrane–bound TF complexes with plasma-derived factor VII or its more active form (VIIa) to directly convert factor X to Xa. TF/VIIa can also indirectly generate Xa by converting factor IX to IXa, which, in turn, complexes with factor VIIIa to convert X to Xa. Factor Xa, once generated, complexes with its cofactor, Va, to convert prothrombin (factor II) to thrombin (IIa). Thrombin activates platelets and cleaves fibrinogen to generate fibrin monomers, which spontaneously polymerize and are cross-linked by thrombin-activated factor XIIIa to form a stable clot. Clotting is restrained by a series of anticoagulant proteins. The initial anticoagulant response is by TF pathway inhibitor (TFPI) that binds to the TF/VIIa/Xa complex to rapidly stop TF-mediated clotting. However, thrombin-activated factor XIa maintains clotting by serving as an alternative activator of factor IX on the surface of platelets. Thus, effective inhibition of the clotting cascade requires prevention of factor IXa- and Xa-mediated clotting. Activated protein C and protein S (APC/S) complex serve this function by inactivating factors VIIIa and Va, respectively. However, the most crucial endogenous anticoagulant system involves antithrombin (AT) inactivation of thrombin and Xa directly. Finally, fibrinolysis breaks down the fibrin clot. Fibrinolysis is mediated by tissue-type plasminogen activator (tPA) that binds to fibrin where it activates plasmin. Plasmin, in turn, degrades fibrin but can be inactivated by α2-antiplasmin embedded in the fibrin clot. Fibrinolysis is primarily inhibited by type-1 plasminogen activator inhibitor (PAI-1), the fast inactivator of tPA. Thrombin activatable fibrinolytic inhibitor (TAFI) is an alternative antifibrinolytic protein.

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As a result of physiologic changes in pregnancy, VTE occurs at a rate that is 4-fold higher compared to the nonpregnant state....

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