Summary. More precise analysis of causes of death is needed to focus research efforts and improve morbidity and mortality in sickle cell disease. In this study, the morphological evidence of the cause of death was studied in 306 autopsies of sickle cell disease, which were accrued between 1929 and 1996. The most common cause of death for all sickle variants and for all age groups was infection (33-48%). The terminal infection was heralded by upper respiratory tract syndromes in 72AE6% and by gastroenteritis in 13AE7%. The most frequent portal of entry in children was the respiratory tract but, in adults, a site of severe chronic organ injury. Other causes of death included stroke 9AE8%, therapy complications 7AE0%, splenic sequestration 6AE6%, pulmonary emboli/thrombi 4AE9%, renal failure 4AE1%, pulmonary hypertension 2AE9%, hepatic failure 0AE8%, massive haemolysis/red cell aplasia 0AE4% and left ventricular failure 0AE4%. Death was frequently sudden and unexpected (40AE8%) or occurred within 24 h after presentation (28AE4%), and was usually associated with acute events (63AE3%). This study shows that the first 24 h after presentation for medical care is an especially perilous time for patients with sickle cell disease and an acute event. Close monitoring and prompt aggressive treatment are warranted.

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The human erythroleukaemic cell line K562, in response to various chemical agents, undergoes differentiation and exhibits exclusive production of fetal and embryonic haemoglobins. In this study we have compared the efficiency of natural growth factors interleukin-3 and erythropoietin and three chemical inducers such as dimethyl sulfoxide (DMSO, 1.9%), phorbol-12-myristate-13-acetate (PMA, 50 ng/ml) and hemin (25 microM) on growth and differentiation of these cells. Erythropoietin significantly stimulated the growth of K562 cells (P<0.0001), while interleukin-3 did not (P = 0.2783). However, neither of these growth factors individually or together induced differentiation of K562 cells. Hemin appears to be more efficient than DMSO or PMA in differentiation of K562 cells as measured by benzidine positive cells (70% or more). The differentiation of K562 cells by hemin occurs independently of protein kinase-C activation and the arrest of DNA synthesis. In contrast, hemin significantly stimulated RNA and protein synthesis (P<0.0001) as measured by [3H]-uridine and [3H]-leucine incorporation respectively. Analysis of hemin-treated K562 nuclear extract on sodium dodecylsulphate gel electrophoresis showed that one protein band of molecular weight 70 kDa decreased after 48 h of incubation in the presence of 25 microM hemin. The disappearance of this protein can be prevented by cycloheximide (100 microg/ml) and actinomycin D (0.1 microg/ml) and thus indicating that the removal of 70 kDa protein seems to be dependent on RNA and protein synthesis. The regulatory role of 70 kDa protein in hemin-induced differentiation of K562 cells is discussed.

Coexistence of sickle cell trait and hereditary spherocytosis (HS) is unusual, and only 16 cases have been reported in the literature. These patients have the same clinical and hematological features as individuals having HS alone. We report a serious complication, acute splenic sequestration crisis (ASSC), occurring in two patients with sickle cell trait and HS. One patient experienced four episodes of ASSC during an 11-year span, while the other had two episodes of this complication during a 4-year period. Red blood cell studies and membrane protein analysis confirmed the diagnosis of HS as a consequence of spectrin deficiency. Splenectomy resulted in marked clinical and hematological improvement in both patients. Histological examination of spleens following splenectomy confirmed that significant erythrostasis and sickling had indeed occurred. ASSC can occur in patients with coexistence of sickle cell trait and HS, and this potentially life-threatening complication should be considered in this condition.

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