Purpose of Study To analyze causes of death among adults with sickle cell disease (SCD) at a single institution over a 25 year period.
Methods A single physician (OC) recorded causes of death among 141 adult SCD patients he treated and knew well from 1976 to 2001. Causes of death were determined by autopsy report and/or clinical assessment.
Results One hundred fourteen (80.9%) of the patients had SS phenotype and 66 (46.8%) were female. The mean ± SD age at death was 36 ± 11 years with a range of 18 to 80 years. The leading causes of death were pulmonary hypertension (PHT) (n = 37; 26.2%), sudden death (n = 33; 23.4%), renal failure (n = 32; 22.7%), sepsis (n = 26; 18.4%), thrombo-embolism (n = 21; 14.9%) and cirrhosis (n = 16; 11.4%). Most patients had more than one diagnosis contributing to death. When causes of death that occurred after 1990 (n = 80) were compared to those that occurred in 1990 or earlier (n = 61), fat embolism was significantly lower (2.5% vs 13.1%; p = 0.02) while the categories of sepsis (25.0% vs 9.8%; p = 0.028) and PHT (38.8% vs 9.8%; p<0.001) were significantly higher after 1990. When associations among various causes of death were explored, significant relations were found between PHT and thrombo-embolism and between cirrhosis and iron overload. Thrombo-embolism contributed to death in 8 (7.7%) of non PHT patients versus 13 (35.1%) of the PHT group (p<0.001). Iron overload contributed to death in 3 (2.4%) of the non-cirrhosis patients versus 7 (43.8%) of the cirrhosis group (p<0.001). Renal failure as a cause of death increased significantly with age (13.5% in patients 30 years and lower vs. 47.4% in patients over 40 years of age; p<0.001)
Conclusions Life expectancy in SCD remains low. The increased diagnosis of pulmonary hypertension as a cause of death since 1990 may be due to increased awareness of this condition and also to SCD individuals with severe disease living long enough to develop this complication. The decreased diagnosis of fat embolism as a cause of death in recent years may be explained by early and aggressive management of acute chest syndrome (ACS) with transfusions, for fat embolism often complicates ACS. The associations of renal disease as a cause of death with increasing age and the finding of a high convergence of iron overload and cirrhosis as causes of death are consistent with current clinical understanding of these conditions. Whether some of the sudden unexplained deaths are due to unrecognized pulmonary hypertension should be investigated in future studies.