1. Sickle Cell Disease Paolo Aquino, M.D., M.P.H., PGY I Combined Internal Medicine/Pediatrics

2. Outline What is sickle cell disease? Epidemiology Manifestations Approach Treatment

3. 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 6 th position –Negatively charged amino acid replaced by neutral amino acid

4. 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

5. 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

6. Manifestations Generally, no symptoms are seen in the 1 st 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

7. 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

8. 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

9. Manifestations Infarcts –Stroke –Kidney Impaired renal function Hyposthenuria Priapism Avascular necrosis

10. Manifestations Acute Chest Syndrome –Fever –Tachypnea –Chest pain –Hypoxia –Hypotension –X-ray findings

11. 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

12. Manifestations Cardiomegaly Gallstones Body habitus –Underweight –Delayed puberty

13. 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

14. Approach History –Pain symptoms Recognition of specific processes –Acute chest syndrome –Cholecystitis –Splenic seqestration –Priapism –Neurological changes

15. Approach Physical examination –General: fussiness, irritability, poor feeding –Vital signs –Neurological –HEENT: icterus, pallor, maxillary hyperplasia –Cardiac: murmur –Respiratory: assymetry of breath sounds

16. Approach Physical examination –Abdomen: assess for spleen, Murphy’s sign –GU: priapism –Extremities: edema, infllammation

17. 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

18. Treatment Hydration- 1.5 times maintenance Analgesia –ibuprofen –Acetaminophen +/- codeine –Ketorolac –Opiates

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

20. Treatment For suspicion of stroke –Exchange transfusion For priapism –Analgesia, hydration –Partial exchange transfusion

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

22. References Nelson’s eMedicine 6 West Handbook