++
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.
++
++
As a result of physiologic changes in pregnancy, VTE occurs at a rate that is 4-fold higher compared to the nonpregnant state.4 The postpartum period is even more thrombogenic, with VTE twice as likely as a given 6-week period during pregnancy. That VTE does not occur more often is remarkable, given the paradoxical challenges presented to the hemostatic system during pregnancy.
++
During early placentation, syncytiotrophoblasts penetrate maternal uterine vessels to establish the primordial uteroplacental circulation. Subsequently, endovascular extravillous cytotrophoblasts invade decidual and superficial myometrial spiral arteries, orchestrating a morphologic conversion of these vessels to achieve high-volume, low-resistance blood flow into the intervillous space. Fetal survival requires that these processes occur in the absence of either significant decidual hemorrhage (ie, abruption) or intervillous thrombosis. To ensure maternal survival, decidual hemorrhage must be avoided throughout pregnancy.
++
The most profound hemostatic challenge is faced by mothers during the third stage of labor. Following separation of the placenta from the uterine wall after delivery of the infant, hemostasis must be rapidly achieved in 140 remodeled spiral arteries to avoid potentially catastrophic hemorrhage. While local factors such as high decidual tissue factor (aka thromboplastin) expression contribute to this placental site hemostasis, dramatic changes in the mother’s expression of clotting and anticlotting factors are also required to meet this hemostatic challenge.
++
In addition to an innate hypercoagulability, venous stasis and vascular trauma complete Virchow classic triad5 (Fig. 7-2). Venous stasis is present as a result of mechanical impedance of the lower extremity vasculature by the gravid uterus, and estrogen-mediated vascular dilation.6 Endothelial damage is often present during the puerperium, especially with operative delivery, hypertensive disease, tobacco use, and infections.
++
++
In a review of International Classification of Disease-9 (ICD-9) codes from over 9 million pregnancy admissions and over 73,000 postpartum admissions in the United States National Inpatient Sample (NIS), a list of medical and obstetric risk factors for VTE was identified. See Tables 7-1 and 7-2 for a listing of common risk factors in the development of VTE.
++
++
++
Patients with underlying hypercoagulable states are at even higher risk for VTE and other obstetric adverse outcomes. These thrombophilic states can be divided into inheritable mutations and acquired disorders.
+++
Inheritable Thrombophilia
++
The most common significant inherited thrombophilias include heterozygosity for the factor V Leiden (FVL) mutation heterozygosity, and prothrombin G20210A (PGM) gene mutations. Rarer causes of inherited thrombophilias include antithrombin (AT) deficiency, protein S deficiency, and protein C deficiency. See Table 7-3 for a summary of these thrombophilias, their respective inheritance patterns, and risks of thromboses.
++
+++
Acquired Thrombophilia
++
The most common acquired thrombophilia is antiphospholipid antibody syndrome (APAS). Approximately 2% of APAS patients will experience a VTE in pregnancy, accounting for approximately 14% of VTE events in pregnancy. Diagnosis of APAS requires one clinical criterion and one laboratory criterion, as defined at the international consensus conference in 2006.8 (See Table 7-4).
++
++
APAS is a thrombogenic disorder that arises from autoimmune targeting of proteins binding to exteriorized anionic phospholipids on endothelial cell membranes, such as cardiolipin and phosphatidylserine. In more than half of APAS patients, the responsible antibodies arise as a result of underlying disorders such as systemic lupus erythematosus (SLE). Diseases such as SLE induce endothelial compromise, which expose the anionic phospholipids that bind to specialized proteins, creating neoantigens recognized by the immune system. The antiphospholipid antibodies increase the thrombogenic potential by inhibiting anionic phospholipid-binding endogenous anticoagulants (such as β2-glycoprotein-I, annexin V, antithrombin, thrombomodulin, proteins C and S) and inducing procoagulants (such as tissue factor, plasminogen activator inhibitor-1, von Willebrand factor, and activation of complement).
++
The type and concentration of antiphospholipid antibody predict its pathogenicity. Low-positive anticardiolipin IgG and IgM are seldom associated with medical complications. Medium or high titers of anticardiolipin and presence of lupus anticoagulant are associated with 4-fold higher rates of thrombosis.
+++
Screening for Thrombophilias in Pregnancy
++
The utility of screening for thrombophilia in pregnancy remains highly debated. The American College of Obstetricians and Gynecologists currently recommend screening in cases where results will affect management decisions such as duration and dosage of treatment.9 Screening may be considered in the following clinical settings:
A personal history of VTE that was associated with a nonrecurrent risk factor (eg, fractures, surgery, prolonged immobilization)
A first-degree relative (eg, parent or sibling) with known high-risk thrombophilia or VTE before age 50 years in the absence of other risk factors
++
Routine screening for inheritable thrombophilias is not recommended in other situations, such as a history of adverse pregnancy outcomes, fetal loss, preeclampsia, fetal growth restriction, and placental abruption. However, screening for acquired thrombophilias, such as antiphospholipid antibodies, may be appropriate in patients with such a history.