Diagnosis of Sickle Cell Disease

Virtually all states in the U.S. have instituted mandatory newborn screening program for sickle cell disease. Such programs identify newborns with the disease, provide prompt diagnosis and anticipatory guidance for the parents, and make possible the initiation of treatment with penicillin before 4 mo of age.

Newborn Screening:
The most commonly used procedures for newborn diagnosis include thin-layer/isoelectric focusing and high-performance liquid chromatography. A 2-step system is recommended, in which all initially abnormal screens are retested during the 1st clinical visit and again after 6 mo of age to determine the final hemoglobin phenotype.

A complete blood cell count as well as hemoglobin analysis is recommended on both parents to confirm the diagnosis and provide an opportunity for genetic counseling.

In affected patients, the red blood cell morphology after 3–6 mo of life is helpful for sickle cell disease and other hemoglobinopathies.

Newborn screening programs 1st report the hemoglobin with the greatest quantity, followed by the other hemoglobins in decreasing quantity. In newborns with a hemoglobin analysis consistent with a diagnosis of sickle cell disease, the FS pattern is supportive of Hb SS, Hb hereditary persistent fetal hemoglobin (Hb S/?0). The FSA pattern is supportive of the diagnosis of Hb S/?+. The diagnosis of Hb S/?+is confirmed if at least 50% of hemoglobin is Hb S, Hb A is present, and an elevated amount of Hb A2is present (typically >3.5%).

In newborns with a hemoglobin analysis of FSC, the pattern is supportive of a diagnosis of Hb SC. In newborns with a hemoglobin analysis of FAS, the pattern is supportive of a diagnosis of Hb AS (sickle cell trait). A newborn with a hemoglobin analysis of AFS may have been transfused with red blood cells before the laboratory test because the amount of Hb A is greater than the amount of Hb F, or an error was made. The patient may have either sickle cell disease (Hb SS, or Hb S/?+) or sickle cell trait, and should be given penicillin prophylaxis until the final diagnosis can be determined.

Given the implications of a diagnosis of either sickle cell disease or sickle cell trait in a newborn, the importance of repeating the hemoglobin analysis in the patient, as well obtaining the hemoglobin analysis and complete blood counts for evaluation of the smear and red blood cell parameters in the parents for genetic counseling, cannot be overemphasized. Mistakes do occur in state newborn screening programs. Newborns who had the initial phenotype of Hb FS, but whose final true phenotype included Hb S/?+, have been described as one of the more common errors identified in the newborn screening hemoglobinopathy programs.