To determine the natural history of sickle cell disease from birth to death in order to identify those factors contributing to the morbidity and mortality of the disease.

BACKGROUND:

Sickle cell anemia (Hb SS) and related hemoglobinopathies involving sickle hemoglobin (HbS) had been recognized for many years and numerous clinical and laboratory manifestations had been described. However, the clinical course of sickle cell disease was poorly documented. The ability to establish concrete interrelationships among signs, symptoms and laboratory test results was complicated by the complexity of the interaction of basic disease processes with other health related events.

Comprehensive evaluations of the clinical status of patients were usually carried out only during hospitalizations for 'crises' or other acute illnesses. Because of this inconsistent nature of the doctor/patient relationships, methods of periodic recording of the patient's status needed to be established. Further, the obtaining of comprehensive laboratory data was necessary during periods of apparent clinical remissions as well as hospitalizations. A well designed, statistically valid, longitudinal study could make a significant contribution to a better understanding of sickle cell disease. Information was particularly lacking on the clinical course starting at birth. Criteria needed to be formulated that could establish classifications of organ involvement and severity of the disease processes. Such classifications could ultimately be used in establishing the need for and evaluating the efficacy of proposed therapies.

The source of the idea for the study dates back to 1971 when the Hematology Study Section recommended in a position paper a study on the natural history of sickle cell disease. The Hemolytic Disease Study Group of the Division of Blood Diseases and Resources developed a detailed protocol in 1973. The National Sickle Cell Disease Advisory Committee endorsed the idea in 1975. In April 1976, the Red Cell Working Group of the Blood Diseases and Resources Advisory Committee recommended initiating the study. The National Heart, Lung, and Blood Advisory Council approved the initiative in December 1976.

Phase I, the Planning Phase, began in 1977. The protocols and Manual of Operations were developed in this phase. Phase II, the Enrollment Phase, began in March 1979 and ended in March 1981, except for infants younger than 6 months of age, who continued to be enrolled after March 1981. In 1983 the study was extended for an additional five years through 1988. Beginning in 1989, as a separate initiative, the study follows selected patient groups from the original study for an additional five years. The selected groups include the newborn cohort and patients surviving beyond age 35.

In 1981, the NHLBI offered a special competition for the evaluation of cardiac function in sickle cell disease patients who were enrolled in the cooperative study of sickle cell disease. The original general study protocol required assessment of the lungs, spleen, kidneys, eyes, and liver but not the heart. The cardiac function study objectives were: to determine cardiac function in a cross-section of sickle cell patients participating in the larger study; to determine the incidence, prevalence, and onset of cardiac impairment; and to assess changes in cardiac function and correlate the observed changes with other clinical data. A total of 300 patients had an entry cardiac evaluation in the third year of the study (June 1, 1981 through November 30, 1981) and an exit cardiac evaluation two years later in the fifth year of the study which was conducted at four centers.

Twelve cooperative study of sickle cell disease centers and eleven other clinical institutions initiated the Penicillin Prophylaxis in Sickle Cell Disease (PROPS I) clinical trial in August 1983. The objective of the trial was to determine whether the regular daily administration of oral penicillin would reduce the incidence of documented infection due to Streptococcus pneumoniae in children aged 3 months to 3 years with sickle cell anemia. The trial was scheduled to end in February 1986 but was terminated eight months early, after an average of 15 months of follow-up, when an 84 percent reduction in the incidence of infection was observed in the penicillin group as compared to the placebo group.

DESIGN NARRATIVE:

Baseline data were collected, including demographic and past medical history and clinical and laboratory information. Stabilized patients were re-examined every six months. Newborns and young infants were re-examined every two to three months. Organ damage to the lungs, spleen, kidneys, eyes, and liver was measured at specific entry and exit points to provide longitudinal data. Data was also gathered on all acute and chronic complications related to sickle cell disease to provide cross-sectional evaluation.

Black males and females with sickle cell disease