High Risk Obstetrics Sickle Cell Disease Case File

High Risk Obstetrics Sickle Cell Disease Case File

Eugene C. Toy, MD, Edward Yeomans, MD, Linda Fonseca, MD, Joseph M. Ernest, MD

Case 31

A 28-year-old African American woman, G2P0101, with sickle cell anemia presented at 21 weeks of gestation with back and hip pain, typical symptoms of her acute painful episodes. She was admitted to the hospital for management. Laboratory studies revealed a hematocrit of 18%, reticulocyte count 27%, total bilirubin 8.2 mg/dL, and direct bilirubin 2.8 mg/dL.

On hospital day 2 the patient developed left-sided chest pain, tachypnea, and progressively worsening hypoxemia. Her oral temperature was 38.8°C and her respiratory rate was 24 per minute. Chest x-ray showed a left lower lobe infiltrate. Repeat hematocrit was 16%.

➤ What is the most likely diagnosis?

➤ What is your next step?

➤ What are potential complications of this patient’s disorder?

ANSWERS TO CASE 31:

Sickle Cell Disease

Summary: This is a 28-year-old African American female, G2P0101, with sickle cell anemia admitted at 21 weeks of gestation with symptoms of an acute vaso-occlusive episode. She developed worsening hypoxemia and her chest x-ray showed a left lower lobe infiltrate.

➤ Most likely diagnosis: Acute chest syndrome.

➤ Next steps: Transfer to ICU or OB critical care unit, supplemental oxygen and respiratory support, transfusion, antibiotics.

➤ Potential complications: Early mortality, restrictive and obstructive lung disease, interstitial fibrosis, pulmonary hypertension, fetal hypoxemia.

ANALYSIS

Objectives

1. Understand the utility and necessity of hemoglobin electrophoresis in the diagnosis of the various sickle hemoglobinopathies.
2. Be able to diagnose and manage the acute chest syndrome.
3. Learn how to provide optimal prenatal care to women with sickle cell anemia.

Considerations

The acute chest syndrome is the second most common cause of hospitalization and the leading cause of admission to an intensive care unit and of premature death among patients with sickle cell disease (SCD). It is generally defined as development of a new pulmonary infiltrate involving at least one complete lung segment, not due to atelectasis, in a patient with SCD.1 Chest pain, fever, tachypnea, wheezing, and cough are usually present in addition to the imaging findings. The syndrome typically develops 24 to 72 hours after the onset of a vaso-occlusive episode, and is often preceded by a drop in hemoglobin level and/or platelet count. Three major causes have been proposed: pulmonary infection, fat embolism, and pulmonary infarction due to intravascular sickling and occlusion.1 A recent case report describes a woman in the third trimester of pregnancy who developed acute chest syndrome precipitated by a lower respiratory infection.2 Surprisingly, this was her first ever manifestation of her underlying sickle cell disease.

Treatment is primarily supportive. Supplemental oxygen and, if needed, mechanical ventilation to maintain a PaO2 of at least 70 mm Hg are essential to prevent further sickling and avoid fetal hypoxemia. Inhaled bronchodilators should be given if there is evidence of bronchospasm. Antibiotic coverage for community-acquired organisms should be administered. Simple or exchange transfusion to increase the hematocrit and reduce the hemoglobin S level often leads to clinical improvement. Opioid analgesics and intravenous hydration should be administered with caution because they may lead to respiratory depression and pulmonary edema.

APPROACH TO

Sickle Cell Disease With Acute Vaso-Occlusive Episode and Acute Chest Syndrome

DEFINITIONS

SICKLE CELL DISEASE (SCD): A group of inherited structural hemoglobinopathies caused by a change in the normal amino acid content of hemoglobin.

ACUTE PAINFUL EPISODE: An episode of acute pain caused by vaso-occlusion in a patient with SCD, previously called sickle cell crisis.

ACUTE CHEST SYNDROME: Development of a new pulmonary infiltrate involving at least one complete lung segment, not due to atelectasis, in a patient with SCD, often accompanied by chest pain, fever, tachypnea, wheezing, and cough.

CLINICAL APPROACH

Etiology

Sickle cell disease refers to a group of inherited structural hemoglobinopathies caused by a change in the normal amino acid content of hemoglobin. Normal adult hemoglobin A is a tetramer composed of two α chains and two β chains. The substitution of valine or lysine for glutamic acid at the sixth position in the β chain produces the two most common structurally abnormal hemoglobins, S and C, respectively. Thalassemia refers to decreased synthesis of normal hemoglobin. Thalassemia syndromes are named by the type of chain that is inadequately produced; for example, in β thalassemia the beta-globin chain is underproduced.

The most common sickle cell diseases, sickle cell anemia (hemoglobin SS disease), hemoglobin SC disease, and hemoglobin S-β thalassemia, are all characterized by chronic hemolytic anemia and vaso-occlusive phenomena. Hemoglobin S polymerizes when oxygen saturation is low, causing erythrocytes to become rigid and distorted in shape, which then leads to structural damage to the cell membrane.3 These changes and other functional red cell alterations lead to impaired blood flow in small vessels, vaso-occlusion, and hemolysis.

Clinical Presentation

The chronic hemolysis of SCD produces a mild to moderate anemia with high-normal or elevated mean corpuscular volume (MCV), reticulocytosis, unconjugated hyperbilirubinemia, elevated LDH, and low serum haptoglobin. Peripheral blood smear usually shows normochromic erythrocytes. Sickled red cells, polychromasia, and Howell-Jolly bodies reflecting hyposplenia may be seen. The characteristic clinical picture in patients with SCD is acute and chronic multisystem organ failure due to repeated episodes of vaso-occlusion. The most common acute event is the acute painful episode, formerly called sickle cell crisis. Patients present with acute pain, most frequently in the back, extremities, joints, and abdomen. Fever and worsening anemia may also be present. Standard laboratory tests cannot distinguish an acute vaso-occlusive episode from the baseline condition. Other causes of pain, fever, and worsening anemia must be excluded. Acute chest syndrome is the second most common acute event, the clinical presentation of which has been discussed previously. Patients with SCD are at increased risk for infection due to splenic dysfunction, especially from encapsulated organisms such as Streptococcus pneumoniae and Haemophilus influenzae. Vaccines against both of these infectious agents are recommended.4 Urinary tract infections are common, particularly in pregnant patients.

Pregnant patients are at increased risk for maternal complications5 because of increased metabolic demands, hypercoagulable state, and venous stasis, and for fetal complications related to compromised placental blood flow. Maternal and fetal complications of SCD are listed in Table 31–1.

Diagnosis

SCD is inherited in a straightforward autosomal recessive pattern. Cellulose acetate gel hemoglobin electrophoresis is the definitive test to identify carriers and those affected with SCD. Individuals of African, African American, Mediterranean, Middle eastern, and Asian Indian descent should be offered this testing because of increased carrier frequencies in these populations. Solubility tests such as Sickledex are not appropriate for screening6 because they will fail to identify carriers of β thalassemia and abnormal hemoglobins other than hemoglobin S. Prenatal diagnosis is available for couples at risk for fetal hemoglobinopathy by analysis of fetal DNA from chorionic villi or amniotic fluid.

Table 31–1 MATERNAL AND FETAL COMPLICATIONS OF SICKLE CELL DISEASE IN PREGNANCY
MATERNAL	FETAL
Acute chest syndrome	Intrauterine growth restriction
Infection	Prematurity
Thrombosis/thromboembolism	Perinatal death
Preeclampsia/eclampsia
PROM/preterm labor
Placental abruption
Death

PROM = premature rupture of membranes. 

Treatment

All patients with SCD should be seen regularly for health care maintenance. For pregnant women, meticulous prenatal care with attention to known complications of SCD may improve outcome. A team approach is optimal, including obstetrics/maternal-fetal medicine, hematology, pain management, and social services. Baseline physical findings and laboratory values should be established. Patients should be immunized against S pneumoniae, H influenzae type B, hepatitis B virus, and influenza. Folic acid requirements are increased due to intense hematopoiesis; a dose of 4 mg/d is recommended.6 Iron stores are increased in most women with SCD due to chronic hemolysis and/or blood transfusions; however, iron deficiency may be present in up to 20%. Accordingly, iron supplementation should be reserved for patients with low plasma iron or serum ferritin. Frequent screening for and treatment of bacteriuria are essential to prevent pyelonephritis, which may precipitate a vaso-occlusive episode.

Pregnant women with SCD are at increased risk for fetal growth restriction, preterm labor, and perinatal mortality. Serial sonograms to monitor fetal growth are recommended. Antepartum testing should be initiated if complications develop; the benefit of routine fetal surveillance in patients with SCD has not been established. The signs and symptoms of preterm labor should be reviewed with the patient at each prenatal visit.

The value of prophylactic blood transfusion in pregnancy is debated. Transfusion has been shown to reduce the incidence of acute painful episodes, but a randomized trial showed no improvement in perinatal outcome.7 Risks include hemolytic transfusion reactions, alloimmunization, and hepatitis.

In most centers management is individualized, with transfusion reserved for patients with prior poor obstetrical outcome or frequent vaso-occlusive episodes.

Acute painful episodes may have no identifiable cause or may be precipitated by infection, dehydration, stress, or weather conditions. Episodes usually last for 2 to 7 days. The mainstays of treatment are exclusion of causes other than vaso-occlusion, hydration, and aggressive opiate pain relief. Supplemental oxygen may reduce sickling in small vessels. Nonsteroidal antiinflammatory drugs, hydroxyurea, and 5-azacytidine, which are commonly used in nonpregnant patients, may have adverse fetal effects and should be avoided. Fetal assessment may demonstrate a nonreactive non-stress test, which will often become reactive with resolution of the painful episode.

Spontaneous labor at term and vaginal delivery are preferred. The patient should have adequate pain relief, oxygenation, and hydration. Epidural analgesia is recommended. Compatible blood should be available and consideration given to preoperative transfusion for severely anemic patients when cesarean section is contemplated. A cord blood sample collected at delivery is useful to screen for hemoglobinopathy in the newborn. Breast-feeding is not contraindicated unless the patient is taking medications that would make it inadvisable. Combined oral contraceptives do not affect the course of SCD, but some recommend against their use because of the potential for thrombosis related to the estrogen component. Intrauterine devices should not be used routinely because of increased risk of infection. Progesterone-only pills, contraceptive implants, and intramuscular medroxyprogesterone may be the best contraceptive options for women with SCD because progesterone has been shown to decrease the incidence of painful episodes.4

Comprehension Questions

31.1 In the sickle mutation of the beta-globin gene, what amnio acid is substituted for glutamic acid?

A. Glycine

B. Valine

C. Lysine

D. Arginine

31.2 Which species of Streptococcus is an encapsulated organism?

A. S pyogenes

B. S agalactiae

C. S pneumoniae

D. S fecalis

31.3 Which of the following methods of contraception is the best option for women with sickle cell disease?

A. Estrogen-containing oral contraceptives

B. Intrauterine device

C. Nuva ring (etonogestrel/ethinyl estradiol vaginal ring)

D. Implanon (etonogestrel) implant

ANSWERS

31.1 B. Valine is substituted for glutamic acid in the sixth position of the beta-globin chain.

31.2 C. S pneumoniae, also known as the pneumococcus, is an encapsulated organism that affects asplenic patients preferentially. Individuals with homozygous SS sickle cell anemia most often suffer auto-infarction of the spleen at an early age.

31.3 D. Preferred contraceptives for women with sickle cell disease are progesterone-only methods: IM medroxyprogesterone, the progesterone-only mini-pill, and implants such as Implanon.

Clinical Pearls

See US Preventive Services Task Force Study Quality levels of evidence in Case 1

➤ Hemoglobin electrophoresis is the recommended test to identify carriers of abnormal hemoglobin and those affected with SCD. Solubility tests such as Sickledex are not appropriate for screening (Level II-3).

➤ Pregnant patients with SCD are at increased risk for maternal and fetal complications including infection, thrombosis, preeclampsia, abruption, preterm labor, fetal growth restriction, and perinatal mortality (Level II-2).

➤ The most common acute events in patients with SCD are painful episodes and acute chest syndrome.The mainstays of treatment of an acute painful episode are oxygen administration, hydration, aggressive opiate pain relief, and exclusion of causes other than vaso-occlusion (Level II-2).

➤ Pregnant patients with SCD should receive folic acid supplementation of 4 mg/d. Iron supplementation should be reserved for those with evidence of iron deficiency (Level III).

➤ Progesterone-only contraceptive pills, implants, and intramuscular medroxyprogesterone may be the best contraceptive options for women with SCD (Level II-3).

REFERENCES

1. Gladwin MT, Vichinsky E. Pulmonary complications of sickle cell disease. N Engl J Med. 2008;359(21):2254-2265. 

2. Campbell K, Ali U, Bahtiyar M. Acute chest syndrome during pregnancy as initial presentation of sickle cell disease: A case report. Am J Perinatol 2008;25:547-550. 

3. Stuart MJ, Nagel RL. Sickle-cell disease. Lancet. 2004;364:1343-60. 

4. Dauphin-McKenzie N, Gilles JM, Jacques E, Harrington T. Sickle cell anemia in the female patient. Obstet Gynecol Surv. 2006;61(5):343-352. 

5. Villers MS, Jamison MG, De Castro LM, James AH. Morbidity associated with sickle cell disease in pregnancy. Am J Obstet Gynecol. 2008;199(2):125.e1-125.e5. 

6. ACOG Practice Bulletin No. 78. Hemoglobinopathies in pregnancy. Obstet Gynecol. 2007;109(1):229-237. 

7. Koshy M, Burd L, Wallace D, Moawad A, Baron J. Prophylactic red-cell transfusions in pregnant patients with sickle cell disease: a randomized cooperative study. N Engl J Med. 1988;319(22):1447-1452.

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