Sickle Cell Disease

Basics

Description

  • Inherited as autosomal recessive hemoglobinopathy characterized by abnormal hemoglobin (HbS) which polymerizes under stress and deforms RBCs, resulting hemolysis, vaso-occlusion, and subsequent tissue ischemia
  • HbS production secondary to a base substitution in β-globin gene resulting in change of a single amino acid in hemoglobin gene
  • Highest occurrence in Africa, specifically regions where malaria is endemic
  • Occurs in people of African, Mediterranean, Middle Eastern, and Asian descent with varying severity
  • Genotypes and severity in African Americans:
    • HbSS, severe
    • HbSC, mild-to-moderate severity
    • HbSβ-thalassemia, mild-to-moderate severity
    • HbAS, sickle cell trait:
      • No manifestation of disease
      • At risk for sudden death with extreme physical exertion, severe hypoxia, severe dehydration, or maternal labor
  • Increased risk of serious pneumococcal bacterial infections as splenic infarction leads to organ dysfunction and inability to fight encapsulated organisms
  • Sepsis secondary to bacteremia, meningitis, and osteomyelitis are the leading cause of death, with most common pathogens including: S. pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Escherichia coli, and Salmonella
  • Clinical hallmark is acute, episodic pain crises leading to organ damage
  • Acute vaso-occlusive pain crisis start as microinfarcts in microvasculature resulting in macroinfarcts and organ infarction
  • Pain crisis usually follows preceding viral/bacterial infection and localizes to abdomen, chest, back, or joints
  • Acute chest syndrome is a pulmonary vaso-occlusive crisis; leading cause of death in children and adults with HbSS:
    • Acute chest pain, pulmonary infiltrates, and arterial hypoxemia
    • Possible trigger includes fat emboli from infarcted bone marrow
  • Neurologic: 25% develop central neurologic complication during lifetime:
    • Secondary to abnormal cerebral blood flow and vaso-occlusive strokes
    • 11% of patients with SCD have an ischemic stroke before age of 20
    • Older adults prone to hemorrhagic strokes
    • Children have a 300-fold increased risk of CVA/TIA, most occurring before the age of 10
  • Cardiopulmonary: Impaired pulmonary function with intrapulmonary arterial-venous shunting leading to pulmonary HTN, cor pulmonale, and LVEF dysfunction
  • Hepatobiliary: Prone to develop gallstones and have baseline abnormal liver function secondary to hepatic vaso-occlusion, hepatitis from blood transfusions, and iron overload
  • Musculoskeletal: Vaso-occlusion within bony matrix leads to aseptic necrosis, often in hips and shoulders:
    • Long bones, ribs, sternum, spine, and pelvis common site for acute pain crisis
  • Dermal: Chronic and refractory ulcerations of lower extremities from combination of minor trauma, local infection, and compromised circulation due to vaso-occlusion
  • Ocular: Leading cause of monocular blindness among people of African ancestry is SCD. Retinal damage from arterial occlusion, hemorrhage, and proliferation of blood vessels secondary to ischemia
  • Genitourinary: Prone to hyposthenuria (inability to concentrate urine), dehydration, painless hematuria, renal failure onset in 50–60s:
  • Males develop low-flow (ischemic) priapism – acute painful engorgement of penis due to vaso-occlusion of corpus cavernosum sinuses

Pediatric Considerations

  • Newborn screening mandatory in most states in US
  • Newborn do not become anemic or have signs/symptoms until at least 6 mo of age
  • Children 6–18 mo of age initially present with dactylitis (hand–foot syndrome) while older children with acute crisis have chest, back, or extremity pain
  • Prone to delayed growth and development
  • Splenic sequestration, aplastic crisis, and dactylitis more commonly observed in children
  • Splenic sequestration: Splenic sinusoids congested with sickled RBCs leading to obstructed outflow, rapidly enlarging spleen, splenic infarction, and precipitous drop in H/H resulting in circulatory collapse:
    • Estimated 6–17% of all SCD deaths
    • More common in children 6 mo–3 yr
  • Aplastic crisis: Self-limiting bone marrow suppression occurring secondary to viral infection, commonly Parvovirus B19. CBC indicates acute anemia with low reticulocyte count
  • Acute vaso-occlusive pain crisis is the most common complication of SCD in children presenting to the ED
  • Children <5 yr with SCD are 400x increased risk of pneumococcal infections due to dysfunctional spleen
  • Confirm immunization history specifically for pneumococcal and H. influenzae type b
  • Ask if child is receiving prophylactic penicillin, normally indicated in children 2 mo–5 yr

Pregnancy Considerations

  • Maternal mortality 10× higher than baseline, with largest majority of death associated at time of delivery
  • Pain and work of labor can precipitate crisis
  • Cardiac dysfunction, pulmonary hypertension, anemia and folate deficiency make it challenge to meet demands of blood volume expansion during pregnancy
  • Increased rates of severe anemia, preeclampsia, urinary tract infections, and pyelonephritis leading to septicemia
  • Increased risk of intrauterine fetal demise, antepartum bleeding, thromboembolic event, premature rupture of membranes, preterm labor, intrauterine growth restriction, and low birth weight

Etiology

Common crisis precipitants:

  • Infection (bacterial and viral)
  • Dehydration
  • Hypoxia
  • Acidosis
  • Stress: Emotional and physical (trauma/surgery)
  • Cold exposure
  • Pregnancy
  • Toxins

There's more to see -- the rest of this topic is available only to subscribers.