Sickle Cell Disease

1. Sickle Cell Disease Joshua Falto PAs-IV

2. PATHOPHYSIOLOGY A single DNA base change leads to an amino acid substitution of valine for glutamine in the sixth position on the B-globin chain. The rate of sickling is influenced by a number of factors, most importantly by the concentration of hemoglobin S in the individual red blood cells (RBCs). RBCs, normally biconcave take on a sickle shape spontaneously or when exposed to infections, dehydration or hypoxic conditions cause painful vaso-occlusive episodes. A drop in temperature, an increase in vasoconstriction can cause sickling of the RBCs as well. EPIDEMIOLOGY Most often found in African-American descent 8-10% of African-Americans carry the trait 0.2% have sickle cell disease A chronic hemoglobinopathy transmitted genetically through an autosomal recessive gene leading to chronic hemolytic anemia. Affects males and females equally General Considerations

3. Chief ComplaintPatient may present with: • Pallor • Symmetric, painful swelling of hands and feet, called hand-foot syndrome • Painful crises in bones, joints, abdomen and back • Scleral icterus (hyper bilirubinemia) • Increased susceptibility to infections

4. Hepatomegaly Splenomegaly Enlarged heart with a hyperdynamic precordium and systolic murmurs. Symmetric, painful swelling of hands and feet Painful crises in bones, joints, abdomen and back Jaundice Nonhealing ulcers of the lower leg Tachycardia during crisis Retinal vessel obstruction Dactylitis on dorsum of hands and feet PHYSICAL EXAM EXPECTED FINDINGS

5. Hemoglobin electrophoresis,(HbS predominates) Screening by Sickledex test or sodium metabisulfite reduction test. Reticulocytes = 10-20% Peripheral blood smear- few sickled RBCS, nucleated RBCs and polychromasia. Elevated bilirubin, Low AST, Elevated Lactate dehydrogenase. Haptoglobin is absent. Bone scans to rule out osteomyelitis. CT and MRI to rule out cerebrovascular accident. LABORATORY TESTS

6. MANAGEMENT PLAN • Treat infections with appropriate antibiotics (early) • Hydration to reduce painful crises as well as adequate analgesia. Twice the normal dose of maintenance fluids (assuming no renal problems). • Chronic maintenance with folic acid supplementation • Hospitalize and Exchange transfusion with vaso-occlusive crises. • Give regular immunizations for pneumococcal pathogens. • Hydroxyurea?

7. Case Patient • 35 yo AA male presents to the ER with complaint of pain in his abdomen, lower back and knee pain (worse in the left leg) for the past 2 days. Patient has a past medical history significant for sickle cell disease with B-thalassemia. • V/s: P106 BP 150/110 T98.6° R24 WT118kg

8. Assessment and Plan • Pain Management: continue analgesics for breakthrough. Demerol 75mg IM q 2°, Visteril 25mg IM q 4°. • Redraw CBC and check WBCs count- possible sepsis work-up needed. • Start IV hydration with Normal saline at 100ml per hr. • Get follow-up chest and abdomen x-rays: possible lower lobe infection of the lungs.

9. Differentials and Provisional Diagnosis • Sickle cell Thalassemia with crisis

10. Have milder form of hemolysis because of the slower rate of sickling Spleen is usually not infarcted MCV is usually low-in contrast to nL of MCV in sickle cell anemia Smear reveals usually fewer irreversible sickle cells Two types: Sickle B° thalassemia is similar to homozygous SS disease and Sickle B+thalassemia (milder crises) Hemoglobin electrophoresis shows absence of Hb- A or increases in Hb-A2 Sickle Thalassemia

11. Which one has sickle cells?