Causes of death in sickle cell disease: an autopsy study.

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 72.6% and by gastroenteritis in 13.7%. 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 9.8%, therapy complications 7.0%, splenic sequestration 6.6%, pulmonary emboli/thrombi 4.9%, renal failure 4.1%, pulmonary hypertension 2.9%, hepatic failure 0.8%, massive haemolysis/red cell aplasia 0.4% and left ventricular failure 0.4%. Death was frequently sudden and unexpected (40.8%) or occurred within 24 h after presentation (28.4%), and was usually associated with acute events (63.3%). 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.

Perivascular fibrosis in the bone marrow in sickle cell disease.

CONTEXT: Magnetic resonance imaging of bone marrow in homozygous sickle cell disease (hemoglobin [Hb] SS) shows nonhomogeneous, mottled signals that increase with age and number of crises. The pattern of these signals is reminiscent of the underlying vascular architecture, but histopathology of this tissue has not been adequately studied. OBJECTIVE: To elucidate the histopathology of blood vessels in the bone marrow in sickle cell disease. DESIGN: Retrospective histochemical morphometric study of bone marrow arteries by point counting in HbSS (13 cases) and sickle cell Hb C (HbSC) (8 cases) compared to nonanemic normal controls (HbAA) (10 cases). All patients were nondiabetic, normotensive, younger than 37 years, and matched for age group. RESULTS: The mean point count for perivascular fibrous tissue was significantly greater in the HbSS group (P <.001) in both small (P <.001) and medium-sized (P =.002) vessels, and in both age groups (pediatric, P <.001; adult, P =.005) compared with the HbAA group. Additional analysis showed the difference was significant in HbSS pediatric small vessels (P <.001) and in pediatric and adult medium vessels (P =.045 and P =.03, respectively). Ratios of fibrous tissue to muscle showed proportionately greater fibrous tissue in HbSS pediatric small (P <.001) and medium-sized vessels (P =.02), and in adult large vessels (P =.03). Mean point counts for muscle were significantly decreased in HbSS small vessels when all ages were compared as a group (P =.02), but when compared by age groups, counts were significantly increased in adult HbSS medium-sized vessels (P =.01). Overall mean point counts for muscle and fibrous tissue in the HbSC group were intermediate between those of the HbSS and HbAA groups, but were not significantly different from counts in the HbAA group (P =.78 and P =.35, respectively). CONCLUSION: In sickle cell disease, arterial vessels in the bone marrow show significantly increased fibrous connective tissue and changes in muscle that vary with age and vessel size.