Sickle cell disease is a hemoglobinopathy caused by a substitution of glutamic acid by valine at the 6th position of the hemoglobin molecule. This leads to rigid, spiny red blood cells that can obstruct blood vessels. Manifestations include painful episodes, acute chest syndrome, infections, strokes, and organ damage to bones, lungs, kidneys, and spleen. Treatment focuses on hydration, pain management, antibiotics, transfusions, and hydroxyurea or bone marrow transplant in severe cases.
Sickle cell disease is a hemoglobinopathy caused by a substitution of glutamic acid by valine at the 6th position of the hemoglobin molecule. This leads to rigid, spiny red blood cells that can obstruct blood vessels. Manifestations include painful episodes, acute chest syndrome, infections, strokes, and organ damage to bones, lungs, kidneys, and spleen. Treatment focuses on hydration, pain management, antibiotics, transfusions, and hydroxyurea or bone marrow transplant in severe cases.
Sickle cell disease is a hemoglobinopathy caused by a substitution of glutamic acid by valine at the 6th position of the hemoglobin molecule. This leads to rigid, spiny red blood cells that can obstruct blood vessels. Manifestations include painful episodes, acute chest syndrome, infections, strokes, and organ damage to bones, lungs, kidneys, and spleen. Treatment focuses on hydration, pain management, antibiotics, transfusions, and hydroxyurea or bone marrow transplant in severe cases.
PGY I Combined Internal Medicine/Pediatrics Outline • What is sickle cell disease? • Epidemiology • Manifestations • Approach • Treatment 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 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 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 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 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 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 Manifestations • Infarcts – Stroke – Kidney • Impaired renal function • Hyposthenuria • Priapism • Avascular necrosis Manifestations • Acute Chest Syndrome – Fever – Tachypnea – Chest pain – Hypoxia – Hypotension – X-ray findings 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 Manifestations • Cardiomegaly • Gallstones • Body habitus – Underweight – Delayed puberty 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 Approach • History – Pain symptoms • Recognition of specific processes – Acute chest syndrome – Cholecystitis – Splenic seqestration – Priapism – Neurological changes Approach • Physical examination – General: fussiness, irritability, poor feeding – Vital signs – Neurological – HEENT: icterus, pallor, maxillary hyperplasia – Cardiac: murmur – Respiratory: assymetry of breath sounds Approach • Physical examination – Abdomen: assess for spleen, Murphy’s sign – GU: priapism – Extremities: edema, infllammation 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 Treatment • Hydration- 1.5 times maintenance • Analgesia – ibuprofen – Acetaminophen +/- codeine – Ketorolac – Opiates Treatment • For respiratory distress – Antibiotic coverage – Supplemental oxygen – Partial exchange transfusion • For splenic sequestration – Repletion of intravascular volume – Severe anemia, transfuse Treatment • For suspicion of stroke – Exchange transfusion • For priapism – Analgesia, hydration – Partial exchange transfusion Treatment • Outpatient – Vaccinations • Pneumococcal, meningococcal, influenza vaccines – Penicillin prophylaxis – ? Folic acid therapy – Hydroxyurea for severe symptoms • Consideration for BMT for severe cases References • Nelson’s • eMedicine • 6 West Handbook