Description

• Sickle cell disease (SCD) is an inherited hematologic disorder that results in the deformation of red blood cells (RBCs) into distorted (sickled), rigid shapes that can block or damage blood vessels, leading to hemolysis-mediated endotheliopathy, ischemic tissue injury, and multiorgan damage (1).
• SCD is associated with increased maternal and fetal morbidity/mortality related to maternal hemolytic anemia and vaso-occlusive multiorgan dysfunction during pregnancy (2).

Epidemiology

• SCD is most common in people of African origin but may be seen in Greeks, Italians (Sicilian), Turks, Arabs, and Asian Indians in high frequency as well (2).
• SCD is found in up to 1 in 600 African Americans (2).
• Some form of SCD is identified in 1 in every 300 African American newborns in the United States (2).
• SCD associated with 4 times increased risk of fetal mortality and 6 times increased risk of maternal mortality (3)

Etiology and Pathophysiology

• SCD is an inherited disorder caused by a homozygous mutation resulting in the formation of hemoglobin S (Hb S) (2).
• RBCs with Hb S are more prone to distortion (sickling) with decreased oxygenation.
• Abnormal RBCs aggregate within organs and small blood vessels.
• Abnormal RBCs lead to increased viscosity, hemolysis, and a shorter half-life.

Genetics

• SCD is inherited in an autosomal recessive form (2).
• Hb has four heme molecules composed of two α-polypeptide and two β-polypeptide chains (2).
• A single nucleotide substitution of thymine for adenine in the β-globin gene results in a substitution of valine for glutamic acid in the number 6 position of the β-globin polypeptide (2).
• Individuals with heterozygous Hb S are considered sickle cell trait carriers. People who are carriers generally do not suffer from the medical complications associated with homozygous Hb SS (2). It is unclear whether pregnant women with sickle cell trait are at greater risk of pregnancy complications and fetal loss (1).
• Sickle cell trait is found in 1 in 12 African Americans (2).
• There are three additional subtypes of SCD, and the disease course is dependent on the SCD genotype. Those with Hb SS and Hb S/β⁰ thalassemia tend to experience greater disease complications and severity than in Hb SC and Hb S/β+ thalassemia carriers, although adverse events have been observed in all subtypes (1).

Risk Factors

Common triggers that may precipitate sickling include cold temperature, physical exertion, dehydration, and low oxygen (O₂) tension (high altitude or scuba diving) (2).

Commonly Associated Conditions

• SCD:
  • Growth and development (2)
    • Retarded growth
    • Skeletal changes
    • Decreased lifespan
  • Sickle cell crisis (2)
    • Painful vaso-occlusive episodes of bones, abdomen, chest, and back
  • Cardiovascular manifestation of hyperdynamic circulation
    • Cardiomegaly
    • Systolic murmurs
    • Heart failure
  • Pulmonary signs
    • Infection: pneumococcus, mycoplasma, Haemophilus, Salmonella
    • Vascular occlusion
  • Abdominal involvement
    • Painful vaso-occlusive episodes
    • Hepatomegaly
    • Hepatitis
    • Cholecystitis
    • Splenic infarction
  • 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
  • Overall, increased risk of infection due to splenectomy due to chronic infarctions (4)
• Sickle cell in pregnancy:
  • SCD in pregnancy is associated with increased maternal and fetal morbidity/mortality related to maternal hemolytic anemia and vaso-occlusive multiorgan dysfunction. The sickling effect of RBCs further increases maternal risk for venothromboembolism (4).
  • One of the common insults to pregnancy is placental insufficiency secondary to chronic hypoxia and placental infarctions due to vaso-occlusion and maternal anemia (4).
  • Patients with homozygous sickle cell and related sickle Hb variants are at high obstetric risk. Consider consult, if available, to obstetricians/perinatologists/hematologists to decrease maternal–fetal morbidity and mortality (2)[C].
  • Risks include (2,3,4,5):
    • Spontaneous abortion and intrauterine fetal death (IUFD) (0 to 20/100 births)
    • Preterm labor and delivery (25.9%)
    • Premature rupture of membranes (0–13%)
    • Intrauterine growth restriction
    • Low birth weight/SGA (16.2%)
    • Fetal anomaly (14.0%)
    • Placental abruption (1.7%)
    • Oligohydramnios (4.4%)
    • Maternal infection (sepsis, pneumonia, UTI)
    • Maternal vaso-occlusive crisis (acute chest syndrome is most severe) (20–50%)
    • Thrombosis (DVT, cerebral vein)
    • Gestational hypertension (HTN), preeclampsia (10.2%), eclampsia
  • Ensure complications of pregnancy are ruled out prior to assuming sickle cells crisis (2)[C].