hematology and oncology
Sickle Cell Disease
Diagnosis of Sickle Cell Disease
DNA testing (prenatal diagnosis) Peripheral smear Solubility testing Hemoglobin electrophoresis (or thin-layer isoelectric focusing) The type of testing done depends on the age of the patient. DNA testing can be used for prenatal diagnosis or to confirm a diagnosis of the sickle cell genotype. Screening of neonates is available in most US states and involves hemoglobin electrophoresis. Screening and diagnosis in children and adults involve examination of the peripheral smear, hemoglobin solubility testing, and hemoglobin electrophoresis. The sensitivity of prenatal diagnosis has been greatly improved with the availability of PCR (polymerase chain reaction) technology. It is recommended for families at risk for sickle cell (eg, couples with medical or family histories of anemia or of suggestive ethnic background). DNA samples can be obtained by Chorionic Villus Sampling at 10 to 12 weeks' gestation. Amniotic fluid can also be tested at 14 to 16 weeks. Diagnosis is important for genetic counseling. Universal testing is currently recommended and is frequently one of a battery of newborn screening tests. To distinguish between hemoglobin (Hb) F, S, A, and C, the recommended tests are hemoglobin electrophoresis using cellulose acetate or acid citrate agar, thin-layer isoelectric focusing, or hemoglobin fractionation by high performance liquid chromatography (HPLC). Repeat testing at age 3 to 6 months may be necessary for confirmation. Solubility testing for Hb S is unreliable during the first few months of life. Patients with a family history of sickle cell disease or trait should be screened with peripheral smear, hemoglobin (Hb) solubility testing, and hemoglobin electrophoresis. Patients with symptoms or signs suggesting the disorder or its complications (eg, poor growth, acute and unexplained bone pain, particularly in the fingers, aseptic necrosis of the femoral head, unexplained hematuria), and patients with African ancestry with normocytic anemia (particularly if hemolysis is present) require laboratory tests for Autoimmune Hemolytic Anemia , hemoglobin electrophoresis, and examination of RBCs for sickling. If sickle cell disease is present, the red blood cell count is usually between 2 and 3 million/microL (2 and 3 x 10 The homozygous state is differentiated from other sickle hemoglobinopathies by electrophoresis showing only Hb S with a variable amount of Hb F. The heterozygote is differentiated by the presence of more Hb A than Hb S on electrophoresis. Hb S must be distinguished from other hemoglobin types with a similar electrophoretic pattern by showing the pathognomonic RBC morphology. Bone marrow examination is not used for diagnosis. If it is done to differentiate other anemias, it shows hyperplasia, with normoblasts predominating; bone marrow may become aplastic during sickling or severe infections. The erythrocyte sedimentation rate, if done to exclude other disorders (eg, juvenile rheumatoid arthritis causing hand and foot pain), is low. Incidental findings on skeletal x-rays may include widening of the diploic spaces of the skull and a sun-ray appearance of the diploic trabeculations. The long bones often show cortical thinning, irregular densities, and new bone formation within the medullary canal. Unexplained hematuria, even among patients not suspected of having sickle cell disease, should prompt consideration of sickle cell trait. If patients with known sickle cell disease have acute exacerbations, including pain, fever, or other symptoms of infection, aplastic crisis is considered and a complete blood count and reticulocyte count are done. A reticulocyte count<1% suggests aplastic crisis, particularly when hemoglobin decreases below the patient’s usual level. In a painful crisis without aplasia, the white blood cell count rises, often with a shift to the left, particularly during bacterial infection. The platelet count is usually increased but can fall with the acute chest syndrome. If measured, serum bilirubin is usually elevated (eg, 2 to 4 mg/dL [34 to 68 micromol/L]), and urine may contain urobilinogen. In patients with chest pain or difficulty breathing, acute chest syndrome and Pulmonary Embolism (PE) are considered; chest x-ray and pulse oximetry are necessary. Because acute chest syndrome is the leading cause of death in sickle cell disease, early recognition and treatment are critical. Hypoxemia or pulmonary parenchymal infiltrates on chest x-ray suggest acute chest syndrome or In patients with fever, infection and acute chest syndrome are considered; cultures, chest x-ray, and other appropriate diagnostic tests are done. 