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Sickle Cell Disease in Pregnancy

Basics

Description

- Hemoglobin has four heme molecules composed of two alpha and two beta polypeptide chains (1). - Sickle cell anemia (SCA) involves formation of abnormal hemoglobin S (Hb S) (1). - Sickle cell disease (SCD) is associated with increased maternal and fetal morbidity/mortality related to maternal hemolytic anemia and vaso-oclusive multiorgan dysfunction. Risks include: (1) - Spontaneous abortion and intrauterine fetal death (IUFD) - Preterm labor and delivery - Premature rupture of membranes - Need for antepartum hospitalization - Intrauterine growth restriction - Low birth weight - Maternal infection - Maternal vaso-oclusive crisis (Acute chest syndrome is most severe.)

- Growth and development (1) - Retarded growth - Skeletal changes - Decreased life span

- Cardiovascular manifestation of hyperdynamic circulation - Cardiomegaly - Systolic murmurs - Failure

- Pulmonary signs - Infection: pneumococcus, mycoplasma, Haemophilus, Salmonella - Vascular occlusion

- Bone and joint changes - Bone marrow infarction - Osteomyelitis: Salmonella - Arthritis

- Genitourinary signs - Hyposthenuria - Hematuria - Pyelonephritis

- Neurologic manifestations - Vascular occlusion - Convulsions - Hemorrhage - Visual disturbances

- Ocular manifestation - Conjunctival vessel change - Vitreous hemorrhage

  • Hemoglobin has four heme molecules composed of two alpha and two beta polypeptide chains (1).
  • Sickle cell anemia (SCA) involves formation of abnormal hemoglobin S (Hb S) (1).
  • Sickle cell disease (SCD) is associated with increased maternal and fetal morbidity/mortality related to maternal hemolytic anemia and vaso-oclusive multiorgan dysfunction. Risks include: (1)Spontaneous abortion and intrauterine fetal death (IUFD)Preterm labor and deliveryPremature rupture of membranesNeed for antepartum hospitalizationIntrauterine growth restrictionLow birth weightMaternal infectionMaternal vaso-oclusive crisis (Acute chest syndrome is most severe.)

Epidemiology

  • SCD is most common in people of African origin but may be seen in Greeks, Italians (Sicilian), Turks, Arabs, Southern Aranians, and Asian Indians in high frequency as well (1).
  • Sickle cell trait is found in 1 in 12 African Americans (1).
  • SCA is found in up to 1 in 600 African Americans (1).
  • Some form of SCD is identified in 1 in every 300 African American newborns in the United States (1).

Etiology and Pathophysiology

  • RBCs with Hb S are more prone to distortion (sickling) with decreased oxygenation.
  • Abnormal RBCs aggregate within organs and small blood vessels.
  • Abnormal RBCs result in increased viscosity, hemolysis, and shorter half-life.

Genetics

  • A single nucleotide substitution of thymine for adenine in the Ä ▓-globin gene results in a substitution of valine for glutamic acid in the #6 position of the Ä ▓-globin polypeptide (1).
  • Carrier has sickle cell trait with heterozygous Hb S, whereas homozygous Hb SS has SCA (1).
  • SCA is inherited in an autosomal recessive form (1).

Risk Factors

Cold temperature, physical exertion, dehydration, and low oxygen tension (high altitude or scuba diving) may precipitate greater sickling (1). é á

Commonly Associated Conditions

  • Growth and development (1)Retarded growthSkeletal changesDecreased life span
  • Sickle cell crisis (1)Painful vaso-occlusive episodes of bones, abdomen, chest, and back
  • Cardiovascular manifestation of hyperdynamic circulationCardiomegalySystolic murmursFailure
  • Pulmonary signsInfection: pneumococcus, mycoplasma, Haemophilus, SalmonellaVascular occlusion
  • Abdominal involvementPainful vaso-occlusive episodesHepatomegalyHepatitisCholecystitisSplenic infarction
  • Bone and joint changesBone marrow infarctionOsteomyelitis: SalmonellaArthritis
  • Genitourinary signsHyposthenuriaHematuriaPyelonephritis
  • Neurologic manifestationsVascular occlusionConvulsionsHemorrhageVisual disturbances
  • Ocular manifestationConjunctival vessel changeVitreous hemorrhage
  • In pregnancy, also related to various forms of gestational hypertension and fetal growth restriction (2)

Diagnosis

History

  • In those with SCA signs and symptoms related to hemolysis, vaso-occlusive disease, or increased susceptibility to infection
  • Description of "typical crisis " Ł and need for blood transfusions
  • SCA patients are usually functionally asplenic, but some have had splenectomy due to sequestration.
  • Determine status of vaccinations.
  • May also take family history to determine possibility of carrier state prior to testing

Physical Exam

  • Routine prenatal exam should be performed (1)[A].
  • Serial fetal ultrasound may be used to assess for growth restriction (1)[C].
  • If sickle cell crisis is suspected, exam should be targeted to areas of suspected damage due to vaso-occlusion (1)[A].
  • Fetal evaluation for well-being by antenatal testing should be done if maternal crisis suspected (1)[B].

Diagnostic Tests & Interpretation

  • Hemoglobin electrophoresis to diagnose Hb S status of patients at recognized risk by ethnicity or family history (1)[A].
  • Avoid use of solubility screens to evaluate for SCA or other hemoglobinopathies (1)[A].
  • Serial complete blood counts to determine degree of anemia throughout pregnancy if SCA (1)[A]
  • Urinalysis +/ ó ł ĺ urine culture should be performed due to increased risk of UTI and pyelonephritis (1)[A].
  • Serial ultrasonography for fetal growth (1)[B]
  • Antenatal testing at the discretion of the physicians (1)[B]

Treatment

General Measures

  • Symptomatic treatment focused on pain control, identification and treatment of infection, and restoration of tissue oxygenation (1)[A]
  • Hydration, oxygen therapy to maintain O2 sat >95% by pulse oximetry, pain management with opiates, and blood transfusion if needed (1)[A]
  • Antibiotics for UTI and pulmonary infections
  • Transfusion therapy if necessary; optimal hematocrit value to guide need for transfusion, and use of prophylactic transfusions still remains controversial and management should be individualized (1)[A].
  • Anemia is common: Do not prescribe iron supplementation without confirmed iron deficiency by serum iron studies.
  • Increased hemolysis and unnecessary iron supplementation may result in iron overload.

Pregnancy Considerations

  • Women with SCD should seek preconception care (3)[B].
  • Prenatal folic acid supplementation with 4 mg/day needed to support rapid turnover of RBCs (1)[A]
  • Ensure complications of pregnancy are ruled out prior to assuming sickle cells crisis (1)[A].
  • Offer testing for father of the baby to determine inheritance risk to the fetus and referral for genetic counseling if the father is an identified carrier (1)[A].
  • Patients with homozygous sickle cell and related sickle hemoglobin variants are at high obstetric risk and require management by obstetricians/perinatologists familiar with this disease working collaboratively with hematologists (1)[C].
  • Management in laborRoutine cesarean delivery not indicated for SCA alone and should only be performed for obstetric indications (1)[A].Epidural analgesia is reasonable with avoidance of hypotension and hypoxemia (1)[B].Prenatal care and delivery should be at a center with resources to support SCA and pregnancy-related complications (3,4)[A].

Medication

First Line

Hydroxyurea é á

  • May increase hemoglobin F production and lead to fewer painful crisis episodes in patients with severe SCA
  • Limited data in pregnancy but known teratogenic in animals. Currently not recommended in pregnancy (1)[A].

Issues for Referral

Should consider referral to obstetrician or maternal " ôfetal medicine specialist due to risk of complications during pregnancy (1)[A] é á

Ongoing Care

Follow-up Recommendations

  • Following resolution of pregnancy, important to discuss contraception and option of sterilization due to the chronic complications associated with SCD and pregnancy
  • Progesterone-only methods have been suggested to prevent painful sickle cell crises.

Patient Monitoring

  • Regular screening for asymptomatic bacteriuria
  • May become anemic: confirm iron deficiency prior to supplementation (1)[A]
  • Serial ultrasounds to monitor normal fetal growth (1)[B]
  • Prenatal vitamins with addition of folic acid (1)[A]

Patient Education

Patients should be encouraged to avoid precipitating factors of painful crisis including (1)[A]: é á

  • Cold environment
  • Heavy physical activity
  • Dehydration
  • Stress

References

1.American College of Obstetricians and é áGynecologists. ACOG practice bulletin no. 78: hemoglobinopathies in pregnancy. Obstet Gynecol. 2007;109(1):229 " ô237. é á

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2.Alayed, é áN, Kezouh é áA, Oddy é áL, et al. Sickle cell disease and pregnancy outcomes: population-based study on 8.8 million births. J Perinat Med. 2014;42(4):487 " ô492. é á

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3.Barfield é áWD, Barradas é áDT, Manning é áSE, et al. Sickle cell disease and pregnancy outcomes: women of African descent. Am J Prev Med. 2014;38(4)(Suppl):S542 " ôS549. é á

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4.Sun é áPM, Wilburn é áW, Raynor é áBD, et al. Sickle cell disease in pregnancy: twenty years of experience at Grady Memorial Hospital, Atlanta, Georgia. Am J Obstet Gynecol. 2001;184(6):1127 " ô1130. é á

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Codes

ICD09

  • 648.20 Anemia of mother, unspecified as to episode of care or not applicable
  • 282.60 Sickle-cell disease, unspecified
  • 282.5 Sickle-cell trait

ICD10

  • O99.019 Anemia complicating pregnancy, unspecified trimester
  • D57.1 Sickle-cell disease without crisis
  • D57.3 Sickle-cell trait

SNOMED

  • 27342004 Anemia of pregnancy (disorder)
  • 127040003 Hereditary hemoglobinopathy disorder homozygous for hemoglobin S (disorder)
  • 16402000 Sickle cell trait (disorder)