Thrombophilias refers to a group of conditions that is associated with (mostly venous) thromboembolism. Venous thromboembolism (VTE) is a leading cause of death in women and is among the top three causes of maternal death in wealthy nations. Moreover, pregnancy and the puerperium are associated with about a 10-fold increase in the risk for VTE with an incidence of approximately one in 1500.1 This increases another threefold to fivefold with cesarean delivery. The hormonal milieu (thought to be primarily due to increased estrogen) of pregnancy leads to a relative increase in procoagulant proteins and a decrease in anticoagulant proteins. It is this delicate balance between procoagulant and anticoagulant proteins that allows for clot formation if there is a cut or injury to a blood vessel, but prevents excessive clot formation so that flow is not impeded. Imbalances in this system may lead to thromboembolism (or bleeding). A list of clotting factors that are altered during normal pregnancy is shown in Table 25-1. In addition, pregnancy is associated with an increased risk for venous stasis and tissue damage (perineal trauma and cesarean delivery). Thus, pregnancy is associated with all of Virchow triad of risk factors for thromboembolism.
TABLE 25-1Changes in the Normal Functioning of the Coagulation System During Pregnancy |Favorite Table|Download (.pdf) TABLE 25-1 Changes in the Normal Functioning of the Coagulation System During Pregnancy
|Coagulant Factors ||Change in Pregnancy |
|Fibrinogen ||Increased |
|Factor VII ||Increased |
|Factor VIII ||Increased |
|Factor X ||Increased |
|Von Willebrand factor ||Increased |
|Plasminogen activator inhibitor-1 ||Increased |
|Plasminogen activator inhibitor-2 ||Increased |
|Factor II ||No change |
|Factor V ||No change |
|Factor IX ||No change |
|Free Protein S ||Decreased |
|Protein C ||No change |
|Antithrombin III ||No change |
Basic schemes of coagulant and anticoagulant pathways are shown in Figures 25-1 and 25-2. Many of the heritable thrombophilias involve the protein C pathway. They typically involve a deficiency, abnormality, or both in anticoagulant proteins, leading to a procoagulant state. However, some thrombophilias, such as the prothrombin G20210A mutation lead to an increase in procoagulant proteins, also increasing the risk for thrombosis. Most thrombophilias are considered to be hereditary. These are usually associated with genetic mutations leading to the abnormalities in anticoagulant or procoagulant proteins. Others are acquired over time, often due to the onset or flare of an autoimmune condition. The acquired thrombophilia that is most common and relevant to obstetricians is an antiphospholipid syndrome (APS). A considerable proportion of thromboses associated with pregnancy occur in women with thrombophilias. Consequently, it is critical for obstetric providers to become familiar with them so as to optimally treat and prevent thromboembolism during pregnancy in women with thrombophilias.
Fibrin plug formation. A, After vascular disruption, factor VII (a) binds to tissue factor (TF) ...
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