During pregnancy, an increase in plasma volume occurs that is greater than the increase in erythrocyte mass, resulting in a physiologic decrease in measured hemoglobin level, although it typically remains greater than 10.5 g/dL (105 g/L). If the hemoglobin level decreases further, additional evaluation of the anemia is warranted. Iron, vitamin B12, and folate levels should be tested.
The physiologic stresses of pregnancy are especially challenging for women with sickle cell disease (SCD). Patients are unable to produce the expected increase in erythrocyte mass, and folate requirements increase because of the rapid turnover of erythrocytes, requiring additional folate supplementation. Iron and vitamin B12 stores must also be monitored. Although expert opinion is not uniform, recent guidelines from the National Institutes of Health did not recommend prophylactic transfusions in pregnancy for women with sickle cell anemia. Other experts disagree, suggesting prophylactic transfusion in pregnant women during the third trimester to achieve a hemoglobin level of 9 g/dL (90 g/L) or reserving such transfusions for women with previous fetal loss, more severe anemia, frequent acute painful events, or history of acute chest syndrome. However, frequent transfusions may lead to alloimmunization, increasing the risk of hemolytic disease of the newborn. Although routine use of prophylactic transfusion is debatable, pregnant women with more severe and symptomatic anemia should be transfused as should any woman with acute chest syndrome or stroke. Pregnant women with SCD should be monitored closely with monthly complete blood counts in collaboration with a hematologist.
In women with SCD, pregnancy affects multiple organ systems in addition to causing anemia. The risk of venous thromboembolism is increased, and prophylactic anticoagulation should be administered in hospitalized patients. The increased cardiopulmonary demands of pregnancy increase the risk of pulmonary hypertension, with an associated 16% mortality risk. Suggestive clinical features should be evaluated by echocardiography.
Medications used to control SCD, such as hydroxyurea and chelating agents, must be discontinued during pregnancy. Painful vaso-occlusive crises increase during pregnancy; pain should be managed with narcotic analgesics, and NSAIDs should be avoided after the 30th week of gestation.
Pregnant patients with SCD are also at increased risk for complications of the pregnancy itself, including intrauterine growth restriction, eclampsia, preterm labor, placental abruption, and stillbirth.
Gestational thrombocytopenia affects approximately 5% of pregnant women. The cause is uncertain, but it may be a milder form of immune thrombocytopenic purpura. Most patients are asymptomatic, with platelet counts greater than 100,000/µL (100 × 109/L), although platelet counts may reach a nadir of 70,000/µL (70 × 109/L). Patients with gestational thrombocytopenia have no history of thrombocytopenia, and the platelet count does not decrease until late in gestation. The fetus is unaffected, intervention is unnecessary, and platelet counts spontaneously return to normal after delivery.
Immune thrombocytopenic purpura (ITP) (see Platelet Disorders) can occur in women of childbearing age and may present during pregnancy. Differentiating ITP from gestational thrombocytopenia may be difficult, but features suggesting ITP include earlier presentation (first trimester), lower platelet count nadir (<70,000/µL [70 × 109/L]), and history of thrombocytopenia before pregnancy (even if it was only mild). If the platelet count remains greater than 30,000/µL (30 × 109/L), the pregnancy is not at risk. Patients should receive intravenous immune globulin or glucocorticoids at any time during pregnancy if the platelet count decreases below 30,000/µL (30 × 109/L). The target platelet count for delivery (vaginal or cesarean section) is 50,000/µL (50 × 109/L), and therapy should begin approximately 1 week before the expected delivery date to achieve that goal. Neuraxial anesthesia requires a platelet count greater than approximately 80,000/µL (80 × 109/L).
ITP autoantibodies can cross the placenta and affect the fetus; 20% to 30% of neonates are reported to have platelet counts less than 50,000/µL (50 × 109/L) (especially if an older sibling was born with thrombocytopenia). Fetal platelet counts can continue to decrease for 2 to 5 days after delivery. Fetal thrombocytopenia is not influenced by maternal treatment with either glucocorticoids or intravenous immune globulin. Despite the increased likelihood of neonatal thrombocytopenia, the risk of intracerebral hemorrhage is less than 1% and is unaffected by delivery by cesarean section.
The thrombotic microangiopathies of pregnancy encompass a spectrum of disorders presenting with clinical features of microangiopathic hemolytic anemia and thrombocytopenia. The differentiating features of these disorders are noted in Table 35.
The distinction between HELLP (Hemolysis, Elevated Liver enzymes, Low Platelets) syndrome, pre-eclampsia, and acute fatty liver of pregnancy may be difficult but is not crucial because management for all of these is supportive and focused on early delivery. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome (see Platelet Disorders) can also occur during pregnancy (see Table 35) and may require additional therapy, including plasma exchange or the anticomplement agent eculizumab.
The risk of venous thromboembolism (VTE) in pregnancy is higher than in the general population, but the absolute risk is still low (<1%). Nevertheless, pulmonary emboli account for about 9% of maternal deaths. The increased risk is a result of venous stasis caused by uterine compression and increased venous capacitance, increased circulating procoagulant factors, and decreased circulating protein S. VTE risk increases further in the postpartum period after endothelial injury during delivery and an additional increase in the procoagulant factors. Factors that further increase VTE risk include multiple births, advanced maternal age, obesity, smoking, cesarean section, and varicose veins.
The possibility of VTE is increased in patients with inherited thrombophilias. However, testing for these disorders in pregnancy is complicated and is not routinely recommended. Deep venous thrombosis most often occurs in the left lower extremity.
Patients with a history of an idiopathic VTE, VTE associated with pregnancy or oral contraceptives, or a hereditary thrombophilia require antenatal and postpartum anticoagulation continuing for 6 weeks following delivery. Low-molecular-weight heparin (LMWH) should be used in the antenatal setting because warfarin is teratogenic and the non–vitamin K antagonist oral anticoagulants have not been studied in pregnancy. LMWH can be transitioned to unfractionated heparin (for its shorter duration of action) around the time of delivery.
Diagnosing a deep venous thrombosis requires evaluation by Doppler ultrasonography. Pulmonary embolism diagnosis in pregnancy presents a challenge because concerns about fetal radiation exposure may limit use of CT angiography, which is the definitive diagnostic test. Although D-dimer levels rise during pregnancy, patients at low risk (Wells score ≤4) who have a normal D-dimer level do not require further evaluation (see Thrombotic Disorders). In women for whom the risk remains moderate or high, a ventilation-perfusion lung scan should be performed. If the ventilation-perfusion scan result is normal, pulmonary embolism is ruled out, and if marked perfusion defects unmatched by ventilation abnormalities are noted, the diagnosis is likely. If the ventilation-perfusion scan result remains indeterminate, the patient should undergo CT angiographic imaging.
LMWH is the treatment of choice for pregnant women with VTE. Therapy should begin with the standard recommended dose and then be titrated to the anti-Xa level because weight-based dosing algorithms that customarily eliminate the need for anti-Xa monitoring may not be reliable during pregnancy. Warfarin is teratogenic and must be avoided in the first trimester, but it is safe to resume after delivery and with breastfeeding. The non–vitamin K antagonist oral anticoagulants have not been evaluated in this setting, so they cannot be recommended. Thrombolytic therapy raises the risk of maternal hemorrhage and should be reserved for life-threatening situations. LMWH must be interrupted at least 24 hours before delivery; unfractionated heparin can be used instead and discontinued as labor progresses or several hours before cesarean section. Postpartum treatment is begun as soon as hemostasis is achieved. Postpartum anticoagulation should continue for at least 6 weeks. The goal is for a total anticoagulation period of 3 to 6 months.