PROGRESS IN THE NATURAL HISTORY STUDIES OF THE CLINICAL SEVERITY OF SICKLE CELL DISEASE: EPIDEMIOLOGIC ASPECTS

Abstract

A prerequisite for the evaluation of any therapeutic modality is a clear understanding of the natural history of the disorder so that an appropriate choice of the high risk patient to treat can be made. In the study of sickle cell anemia, we have chosen hospital admissions as the most consistent measure of illness. Cohort analysis with age stratification does have validity but depends on large numbers of cases observed for many person years. This provides one measure of clinical severity and includes risk and frequency indices. Among the epidemiologic problems encountered in the Los Angeles Natural History Study of Sickle Cell Disease are (a) delineation of the specific characteristics that define clinical severity, and (b) the data retrieval requirements for a cohort analysis because insufficient numbers of patients have been followed since birth. Despite these constraints, our data support the following conclusions: Age and hemoglobinopathy diagnosis are the only consistent variables that predict clinical manifestations. In a population with HbS as the major component and without HbA, our preliminary results show that levels of F, A 2 , MCV, MCH or hemoglobin concentration do not influence the morbidity of sickle cell disease. No predicting factors can reproducibly identify that patient who will manifest pneumococcal septicemia, cerebral vascular accidents, or death. We conclude that the severity of the clinical illness in any given patient is more affected by specific organ damage than by any biochemical or hematologic factor.