Sickle Cell Disease

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Sickle Cell Disease

• Paolo Aquino, M.D., M.P.H.,
• PGY I
• Combined Internal Medicine/Pediatrics

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Outline

• What is sickle cell disease?
• Epidemiology
• Manifestations
• Approach
• Treatment

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What is it?

• Sickle cell disease is one form of
  hemoglobinopathy- a structural abnormality in
  hemoglobin molecule
• Substitution of glutamic acid by valine at the
  6th position
• Negatively charged amino acid replaced by neutral
  amino acid

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What is it?

• Hgb S maintains normal function in oxygenated
  state
• In de-oxygenated state- induced change in
  configuration allows valine to interact
  irregularly
• Formation of highly ordered polymers
• Polymers aggregate to rigid rods
• Spiny brittle RBCs
• Within vessels, thrombosis/obstruction

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Frequency

• 8-10 of African Americans in the U.S. are
  carriers of Hgb S gene
• Hgb SS disease occurs in 0.15 of African
  American newborns

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Manifestations

• Generally, no symptoms are seen in the 1st 6
  moths of life due to circulating fetal hemoglobin
• Dactylitis (aka hand-foot syndrome)
• Painful, symmetric swelling of hands and feet
• Due to ischemic necrosis of small bones of hands
  and feet
• ? Due to rapidly expanding bone marrow, choking
  of blood supply

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Manifestations

• Acute pain episodes
• Young children- extremities
• Older patients- head, chest, abdomen, back
• Recurrence of pain tends to occur in same sites
  within a particular individual
• Exacerbated by fever, hypoxia, acidosis- promote
  deoxygenation of Hgb S

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Manifestations

• Infarctions
• Bone/bone marrow
• Osteomyelitis- concern of salmonella infection
• Autosplenectomy
• Increased susceptibility to encapsulated
  organisms
• Esp. pneumococcus H. influenzae
• Associated with reduction in serum opsonins
• Pulmonary infarcts
• Pneumonitis
• Fat emboli

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Manifestations

• Infarcts
• Stroke
• Kidney
• Impaired renal function
• Hyposthenuria
• Priapism
• Avascular necrosis

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Manifestations

• Acute Chest Syndrome
• Fever
• Tachypnea
• Chest pain
• Hypoxia
• Hypotension
• X-ray findings

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Manifestations

• Splenic seqestration
• Large amounts of blood pools in spleen
• Splenic enlargement
• Criculatory collapse
• Reason unknown
• May follow febrile illness
• Aplastic episodes- may follow infection with
  parvovirus B 19

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Manifestations

• Cardiomegaly
• Gallstones
• Body habitus
• Underweight
• Delayed puberty

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Manifestations

• Laboratory
• Normocytic anemia- Hgb 5-9 mg/dL
• Peripheral smear
• Target cells
• Poikilocytes
• Sickled cells
• Howell Jolly bodies
• Leukocytosis with neutrophil predominance
• Thrombocytosis
• X-ray- expanded marrow spaces, osteoporosis

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Approach

• History
• Pain symptoms
• Recognition of specific processes
• Acute chest syndrome
• Cholecystitis
• Splenic seqestration
• Priapism
• Neurological changes

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Approach

• Physical examination
• General fussiness, irritability, poor feeding
• Vital signs
• Neurological
• HEENT icterus, pallor, maxillary hyperplasia
• Cardiac murmur
• Respiratory assymetry of breath sounds

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Approach

• Physical examination
• Abdomen assess for spleen, Murphys sign
• GU priapism
• Extremities edema, infllammation

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Approach

• Work-up
• Newborn screen
• CBC, reticulocytes, peripheral smear
• If febrile, blood culture
• If lung findings, chest x-ray, blood gas
• If abdominal pain, liver enzymes, UA, abdominal
  u.trasound
• Consider x-ray of extremities
• Head CT if neurological changes

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Treatment

• Hydration- 1.5 times maintenance
• Analgesia
• ibuprofen
• Acetaminophen /- codeine
• Ketorolac
• Opiates

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Treatment

• For respiratory distress
• Antibiotic coverage
• Supplemental oxygen
• Partial exchange transfusion
• For splenic sequestration
• Repletion of intravascular volume
• Severe anemia, transfuse

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Treatment

• For suspicion of stroke
• Exchange transfusion
• For priapism
• Analgesia, hydration
• Partial exchange transfusion

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Treatment

• Outpatient
• Vaccinations
• Pneumococcal, meningococcal, influenza vaccines
• Penicillin prophylaxis
• ? Folic acid therapy
• Hydroxyurea for severe symptoms
• Consideration for BMT for severe cases

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References

• Nelsons
• eMedicine
• 6 West Handbook