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Anemia, Sickle Cell (SCD)

Description:
- Hereditary hemoglobinopathy with chronic hemolytic anemia, acute painful crises, infection risk.
- Heterozygous HbAS (sickle cell trait) usually asymptomatic.
- Synonyms: sickle cell disease (SCD), HbSS disease.

Pediatric Considerations

  • Sequestration crises and hand-foot syndrome typically in infants/young children.
  • Stroke mainly in childhood.
  • Adolescence/young adulthood: increasing complications and organ damage.
  • Psychological issues: body image, interrupted schooling, activity restrictions, stigma, low self-esteem.

Pregnancy Considerations

  • Complicated, especially 3rd trimester and delivery.
  • Fetal mortality 35-40%, survival >90% if reaching 3rd trimester.
  • 6x higher maternal mortality.
  • Risks: thrombosis, preterm delivery, pain, toxemia, infection, pulmonary infarction, phlebitis.
  • Partial exchange transfusion in 3rd trimester may reduce morbidity but controversial.
  • Chronic transfusions reduce pain episodes but risk alloimmunization.

Epidemiology

  • ~100,000 Americans with SCA; ~3 million with sickle cell trait.
  • Mainly affects African descent; also Hispanic, Middle Eastern, Asian Indian, Mediterranean ancestry.

Etiology and Pathophysiology

  • HbS: valine replaces glutamic acid in β-globin chain → polymerization under deoxygenation.
  • Sickled RBCs: increased adhesion, inflexible, cause vasoocclusion → ischemia.
  • Crises types:
  • Vaso-occlusive: tissue ischemia, necrosis, organ damage.
  • Hand-foot syndrome: small vessel occlusion in extremities.
  • Aplastic crisis: suppressed RBC production, often viral.
  • Hyperhemolytic crisis: accelerated hemolysis, reticulocytosis.
  • Sequestration crisis: splenic blood pooling in young children.
  • Infection susceptibility due to impaired splenic function and complement defects.

Genetics

  • Autosomal recessive: homozygous HbSS; heterozygous HbAS.
  • Compound heterozygous states: HbSC, Sβ+ thalassemia (mild), Sβ thalassemia (severe).

Risk Factors for Crises

  • Vaso-occlusive: hypoxia, dehydration, high altitude, stress, fever, infection, acidosis, cold, anesthesia, strenuous exercise, alcohol, smoking.
  • Aplastic: infections (parvovirus B19), folic acid deficiency.
  • Hyperhemolytic: bacterial infections, oxidant exposure.

General Prevention

  • Avoid hypoxia, dehydration, cold, infection, fever, acidosis, anesthesia.
  • Promptly manage fever, infections, and pain.
  • Avoid alcohol, smoking, high altitude.
  • Use aseptic technique to minimize trauma.

Diagnosis

History

  • Usually asymptomatic in early infancy (due to fetal Hb).
  • After 6 months: irritability, painful swelling (hand-foot), infections (pneumococcal sepsis), severe anemia, splenic enlargement.
  • Older children: anemia, recurrent pain, aplastic crisis, acute chest syndrome, splenic sequestration, cholelithiasis.
  • Pain crises common hospital admission cause.
  • Acute chest syndrome: tachycardia, fever, bilateral pulmonary infiltrates.

Diagnostic Tests

  • Screening: Sickledex, hemoglobin electrophoresis (diagnostic).
  • SCA (FS pattern): 80-100% HbS, variable HbF, no HbA1.
  • Trait (FS pattern): 30-45% HbS, 50-70% HbA1, minimal HbF.
  • Labs: Hgb 5-10 g/dL; normal/increased MCV; increased MCHC; reticulocytes 3-15%.
  • Peripheral smear: sickled RBCs, nucleated RBCs, Howell-Jolly bodies.
  • Elevated bilirubin (2-4 mg/dL), ferritin (multiple transfusions), LDH.
  • Haptoglobin absent/low.
  • Urinalysis: hemoglobinuria, hematuria (trait may have painless hematuria), albuminuria monitoring.
  • Imaging: bone scan (rule out osteomyelitis), CT/MRI brain (CVA), chest x-ray (enlarged heart, infiltrates), transcranial Doppler (stroke risk), ECG, echocardiogram.

Treatment

General Measures

  • Hydration, analgesia for pain crises; oxygen irrespective of hypoxia.
  • Retinal screening from school age.
  • Occupational, cognitive, behavioral therapies; support groups.
  • Standard childhood vaccines + special vaccines (influenza, pneumococcal, meningococcal per schedule).

Medication

FDA-Approved:

  • Hydroxyurea (≥9 months): reduces pain & acute chest syndrome; initial 20 mg/kg daily; max 2,500 mg/day.
  • L-glutamine (≥5 years): reduces vaso-occlusive episodes; dose weight-based.
  • Crizanlizumab (≥16 years): reduces vaso-occlusive events; IV dosing schedule.
  • Voxelotor (≥4 years): increases Hgb; weight-based dosing.

Antibiotics:
- Prophylactic penicillin from 2 months to age 5 (or alternative amoxicillin).

Pain management:
- Mild crises: nonopioids (ibuprofen).
- Severe crises: parenteral opioids, PCA pump, careful monitoring.

Acute chest syndrome:
- Oxygen, analgesics, antibiotics, simple/exchange transfusion.

Second Line

  • Folic acid supplementation by age.

Additional Therapies

  • Transfusion for acute episodes and complications.
  • Chelation (deferasirox) for multiple transfusions.
  • Red cell exchange to reduce HbS <30% and prevent iron overload.

Surgery/Other

  • Hematopoietic stem cell transplant (curative).
  • Emerging therapies: endothelin-1 antagonists, monoclonal antibodies (P-selectin).

Admission Criteria

  • Severe pain, suspected infection/sepsis, acute chest syndrome.

Ongoing Care

Follow-Up

  • Early infection treatment; fever ≥101°F requires urgent care.
  • Monitor hepatitis C, hemosiderosis in chronically transfused.
  • Eye exams from age 10 (proliferative retinopathy).
  • Biannual hepatic, renal, pulmonary function exams.
  • Stroke risk: transcranial Doppler 2-16 years.
  • Pulmonary evaluation, echocardiography, right heart cath as indicated.
  • Annual albuminuria screening; ACE/ARB therapy if positive.
  • Shared decision on VTE prophylaxis.

Diet

  • Avoid alcohol (dehydration risk).
  • Maintain hydration.
  • Multivitamin without iron (risk of iron overload).
  • Vitamin D deficiency and bone marrow density concerns.

Prognosis

  • Onset in infancy; crises begin at 1-2 years.
  • Adult median death age: 42 years (men), 48 years (women).

Complications

  • Alloimmunization, bone infarcts, osteomyelitis, avascular necrosis.
  • Cerebral strokes, impaired mental development.
  • Cholelithiasis, liver dysfunction.
  • Chronic leg ulcers, poor wound healing.
  • Impotence, priapism, renal complications.
  • Retinopathy, splenic infarction by age 10.
  • Acute chest syndrome leading to chronic pulmonary disease.
  • Infection-related morbidity and mortality.
  • Hemosiderosis (transfusion related).
  • Opioid tolerance and substance abuse risk.

References

  1. Kavanagh PL, Fasipe TA, Wun T. Sickle cell disease: a review. JAMA. 2022;328(1):57-68.
  2. Brandow AM, Liem RI. Advances in diagnosis and treatment of sickle cell disease. J Hematol Oncol. 2022;15(1):20.
  3. Parikh T, Goti A, Yashi K, et al. Pediatric sickle cell disease and stroke: literature review. Cureus. 2023;15(1):e34003.

See Also

  • Algorithm: Anemia

ICD10 Codes

  • D57.212 Sickle-cell/Hb-C disease with splenic sequestration
  • D57.211 Sickle-cell/Hb-C disease with acute chest syndrome
  • D57.21 Sickle-cell/Hb-C disease with crisis

Clinical Pearls

  • Use 1/2 normal saline as NS may increase sickling risk.
  • Pain crises cause 90% of hospital admissions.
  • Pain management should be individualized and protocol-driven.