Williams Manual of Pregnancy Complications, 23 ed.

CHAPTER 69. Hemoglobinopathies

Sickle-cell anemia (SS disease), sickle-cell hemoglobin C disease (SC disease), and sickle-cell β-thalassemia disease (S-β-thalassemia disease) are the most common of the sickle hemoglobinopathies. Maternal morbidity and mortality, abortion, and perinatal mortality are all increased with these hemoglobinopathies.

SICKLE-CELL TRAIT

The inheritance of the gene for hemoglobin S from one parent and for hemoglobin A from the other results in sickle-cell trait. Sickle-cell trait does not influence the frequency of abortion, perinatal mortality, low birth weight, or pregnancy-induced hypertension. Urinary infection, however, is about twice as common in this group.

HEMOGLOBIN C

Hemoglobin C trait does not cause anemia, nor does it predispose to adverse pregnancy outcomes. When coinherited with sickle-cell trait, however, the resultant hemoglobin SC causes the problems to be discussed in this chapter.

THALASSEMIAS

The genetically determined hemoglobinopathies termed thalassemias are characterized by impaired production of one or more of the normal globin peptide chains. Abnormal synthesis rates may result in ineffective erythropoiesis, hemolysis, and varying degrees of anemia. The different forms of thalassemia are classified according to the globin chain that is deficient in amount compared with its partner chain. The two major forms involve either impaired production of α-peptide chains, causing α-thalassemia, or of β-chains, causing β-thalassemia. The incidence of these traits during pregnancy for all races is probably 1 in 300 to 500.

DIAGNOSIS

According to the American College of Obstetricians and Gynecologists (The use of hormonal contraception in women with coexisting medical conditions, Practice Bulletin No. 18, July 2000), when sickle screening is indicated a hemoglobin electrophoresis is the primary test. In those patients at increased risk for α- or β-thalassemia, screening begins with an evaluation of the red blood cell indices. If the mean corpuscular volume (MCV) is low (less than 80 fL) and iron-deficiency anemia has been ruled out, hemoglobin electrophoresis testing should follow. Elevated hemoglobin A2 level (more than 3.5 percent) or elevated hemoglobin F level (1 to 10 percent) suggests the presence of the β-thalassemia gene. If the MCV is low, iron deficiency is not present, and the hemoglobin electrophoresis is not consistent with β-thalassemia trait, then DNA-based testing is in order to detect α-globin gene deletions that are characteristic of α-thalassemia.

MANAGEMENT

Adequate management of pregnant women with sickle-cell anemia or other sickle-cell hemoglobinopathies necessitates close observation with careful evaluation of all symptoms, physical findings, and laboratory studies. The folic acid requirements are considerable, and supplementary folic acid of 4 mg/day is given.

There are special circumstances during pregnancy that increase appreciably the morbidity of these women. Covert bacteriuria and acute pyelonephritis are increased substantively, and careful surveillance for bacteriuria and its eradication are important to prevent symptomatic urinary tract infections. Pneumonia, especially due to Streptococcus pneumoniae, is common. Polyvalent pneumococcal vaccine is recommended for these women. Influenza vaccine should be given annually.

Women with sickle-cell anemia rarely die of heart disease, but almost all of these women eventually have some degree of cardiac dysfunction. Chronic hypertension will worsen this. Although most of these women tolerate changes of pregnancy without problems, when complications such as severe preeclampsia or serious infections develop, ventricular failure may ensue. Heart failure caused by pulmonary hypertension must also be considered. Shown in Table 69-1 are maternal complications associated with sickle-cell syndromes.

TABLE 69-1. Increased Rates for Maternal Complications of Pregnancies Complicated by Sickle-Cell Syndromes

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Sickle-Cell Crisis

Red blood cells with hemoglobin S undergo sickling when they are deoxygenated and the hemoglobin aggregates. Clinically, the hallmark of sickling episodes is periods during which there is ischemia and infarction within various organs. These changes produce clinical symptoms, predominately pain, and are called “sickle crisis.” Relief of pain from intravascular sickling is not afforded by heparinization or dextran. To maintain blood volume, intravenous hydration is given, along with meperidine or morphine administered parenterally for severe pain. Many of these women frequently are dehydrated due to diminished oral intake secondary to pain and they often have fever, which exacerbates their hypovolemia. Oxygen given via nasal cannula may increase oxygen tension and decrease the intensity of sickling at the capillary level. We have found that red blood cell transfusions after the onset of severe pain do not dramatically improve the intensity of the pain and may not shorten its duration. Conversely, prophylactic red blood cell transfusions almost always eliminate pain episodes by preventing vasoocclusive crises.

One rather common danger is that the symptomatic woman may categorically be considered to be suffering from a sickle-cell crisis. As a result, ectopic pregnancy, placental abruption, pyelonephritis, appendicitis, cholecystitis, or other serious obstetrical or medical problems that cause pain, anemia, or both, may be overlooked. The term “sickle-cell crisis” should be applied only after all other possible causes of pain or fever or reduction in hemoglobin concentration have been excluded.

As many as 40 percent of patients suffer from a serious and frequent complication known as acute chest syndrome. It is characterized by pleuritic chest pain, fever, cough, lung infiltrates, and hypoxia.

Assessment of Fetal Health

Because of the high incidence of fetal growth restriction and perinatal mortality, serial fetal assessment is necessary. The American College of Obstetricians and Gynecologists: Hemoglobinopathies in pregnancy. Practice Bulletin No. 78, January 2007 recommends weekly antepartum fetal surveillance beginning at 32 to 34 weeks. Serial ultrasonography is usually done to monitor fetal growth and amnionic fluid volume. At Parkland Hospital, we serially assess these women with ultrasound to determine amnionic fluid volume and follow fetal growth. Nonstress or contraction stress tests are not done routinely unless fetal movement is reported to be diminished or other significant complications develop that prompt admission.

Delivery

Labor and delivery in women with hemoglobin SS disease should be managed the same way as for women with cardiac disease (see Chapter 48). Epidural analgesia is ideally suited for labor and delivery. Compatible blood should be available. If a difficult vaginal or cesarean delivery is contemplated, and the hematocrit is less than 20 percent, the hemoglobin concentration should be increased by packed erythrocyte transfusions. At the same time, care must be taken to prevent circulatory overload from ventricular failure and pulmonary edema.

Prophylactic Red Blood Cell Transfusions

There currently is a controversy over the use of prophylactic transfusions during pregnancy for women with sickle-cell syndromes. The incidence of painful sickle-cell crises and complications is decreased in women transfused prophylactically. Current consensus is that either prophylactic transfusions or transfusions only when indicated may be appropriate for a particular woman. Some clinicians choose prophylactic transfusions in women with a history of multiple vaso-occlusive episodes and poor obstetrical outcomes.

Contraception and Sterilization

In women with sickle-cell trait, combination oral contraceptives (OCs) may be used. In patients who have a sickle hemoglobinopathy, clinical judgment and informed consent are warranted. The consensus is that pregnancy carries a greater risk than combination OCs in these high-risk women; however, recommendations regarding OC use vary widely. Many authors do not recommend their use because of potential adverse vascular and thrombotic effects. Depo medroxyprogesterone acetate may be an appropriate contraceptive for these women because it has been shown to reduce the incidence of painful crises and improve anemia. Intrauterine devices are probably contraindicated because of the increased risk of infection. Unfortunately, the safest contraceptives available are also the ones with the highest failure rates (condoms, foam, diaphragms). Permanent sterilization may be offered to parous women.


For further reading in Williams Obstetrics, 23rd ed.,

see Chapter 51, “Hematological Disorders.”