Causes of death in sickle cell disease: an autopsy study

Abstract BACKGROUND: In the early 1990’s, the Cooperative Study of Sickle Cell Disease (CSSCD) estimated a median life expectancy of 42 years for males, and 48 years for females with sickle cell anemia. We used death certificate data from the late 1990’s and early 2000’s to examine age at death and contributing causes of death for persons with sickle cell disease (SCD). METHODS: We used the National Center for Health Statistics Multiple Cause of Death (MCOD) files to examine age at death and contributing causes of death for persons in the U.S. with SCD during the years 1999 to 2004. The MCOD files contain data from all death certificates filed in the U.S. Each observation in the data has listed an underlying (primary) cause of death, as well as up to 20 conditions thought to contribute to the death. We used ICD-10 codes D570-D578 to identify all deaths attributed to SCD during the time period under study. Records with the ICD-10 code for sickle cell trait (D573) were excluded from further analyses. We used the Clinical Classification Software provided by the Healthcare Cost and Utilization Project to collapse all listed ICD-10 codes into smaller categories. Analyses of age at death were conducted using t-tests, median tests, ANOVA, and multiple linear regression as appropriate. RESULTS: From 1999 to 2004, there were 4553 deaths in the U.S. attributed to SCD (mean = 759/yr, sd = 42.6). SCD was listed as the primary cause in 65% of the deaths. 95% of the deaths were attributed to HbSS disease, and approximately 1% of the deaths were attributed to double heterozygous sickle cell disorders (SC/SD/SE/Thal). 50.4% of the deaths were among males. 64% of the decedents had a high school education or less. 54% of the decedents lived in the South. 68% of the decedents died as inpatients in a hospital. The mean age at death for the time period was 38.2 years (sd = 15.6). There was no change in the mean age at death during the time period. Females were older than males at death (39.4 vs. 36.9, p < 0.0001). Those with HbSS were younger than those with a double heterozygous disorder (38 vs. 47, p < 0.02). Having SCD listed as the primary cause of death was associated with younger age at death (36.8 vs. 40.7, p < 0.0001). Decedents with at least some college education were older at death than those with high school educations or less (40.9 vs. 37.0 p < 0.0001). There were no regional differences in mean age at death. In a multivariate model of age at death with the predictors gender, region, education, and whether or not SCD was listed as the primary cause of death, being female and having some college education remained associated with older age at death, while having SCD listed as the primary cause of death remained associated with younger age at death. Septicemia, pulmonary heart disease, liver disease and renal failure were among the top contributing causes of death for adults, while septicemia, acute cerebrovascular disease and pneumonia were among the top contributing causes of death for kids. CONCLUSIONS: Persons dying from SCD during 1999 to 2004 experienced ages at death that are not improved over those reported by the CSSCD, suggesting the continued need for societal efforts aimed at improving the quality of care for SCD, especially among adults with the condition. Educational attainment is associated with age at death among the SCD population, though it is not possible from the cross-sectional nature of this data to determine the causal directionality of this association.

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47 CAUSES OF DEATH IN ADULT SICKLE CELL DISEASE PATIENTS AT HOWARD UNIVERSITY

Journal of Investigative Medicine ◽

10.2310/6650.2005.00205.46 ◽

2005 ◽

Vol 53 (2) ◽

pp. S395.2-S395

Author(s):

D. S. Darbari ◽

J. Kwagyan ◽

S. Rana ◽

V. R. Gordeuk ◽

O. Castro

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Causes Of Death ◽

Cell Disease ◽

Howard University

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Hematological and Clinical Findings Predictive of Mortality in Italian Patients with Sickle-Cell Disease: A Case-Control Study.

Blood ◽

10.1182/blood.v108.11.3780.3780 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3780-3780

Author(s):

Aurelio Maggio ◽

Veronica Di Salvo ◽

Paolo Rigano ◽

Antonino Giangreco ◽

Maria Concetta Renda ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Causes Of Death ◽

Case Control Study ◽

Case Control ◽

Clinical Findings ◽

Cell Disease ◽

Previous Stroke ◽

Wbc Count ◽

Control Study

Abstract Background: the number of cases with Sickle-Cell Disease (SCD) registered in Italy at 2000 was 928. Six-hundred-twenty-two (67%) of these were with Sickle-Cell/βthalassemia. Moreover, while the main causes of death in Afro-American patients with SCD is well known, we do not have many informations in Italian subjects. For this reason, we carried ahead a case-control study in this group of patients. Aim of the study: the evaluation of the main hematological and clinical parameters predictive of mortality. Materials and Methods: clinical and hematological findings of 14 SCD died patients were compared with a SCD alive control population homogeneous for age, sex, phenotype and number of painful crises per year. Two alive control subjects were studied for each died patient. Results: the main causes of death were: Acute Chest Syndromes (ACS) (n°6), Cardiovascular Diseases (n°3),Hepatic Failure (n°1),Hodgkin Lymphoma (n°1), Stroke (n°1), Lung Cancer (n°1), Surgery Complication (n°1). The main correlated hematological findings with mortality were Hb (gr/dl) levels (p=<.05), WBC count (103 / ml) (p= <.05), ferritin levels (ng/ml) (p=<.01). The main correlated clinical features were: the number of crises >3/year (Odd Ratio= 1.64; p= <.01), previous stroke (Odd Ratio= 1.53; p= <.01), HU treatment (Odd Ratio=<.01; p=<.01), leg ulcers (Odd Ratio=1.46;p=<.01). Conclusions: these data suggest that the main causes of death in Italian patients with SCD are similar to those reported for Afro-American subjects (M.H. Steinberg, JAMA, April 2, Vol. 289, N°13, 1645–1651). Particularly, the lack of HU treatment, anemia, high ferritin levels, number of crises per year and previous stroke are the most important predictive factors of mortality.

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Mortality and causes of death in children with sickle cell disease in the Netherlands, before the introduction of neonatal screening

British Journal of Haematology ◽

10.1111/j.1365-2141.2011.08806.x ◽

2011 ◽

Vol 155 (1) ◽

pp. 106-110 ◽

Cited By ~ 16

Author(s):

Evelyn M. van der Plas ◽

Xandra W. van den Tweel ◽

Ronald B. Geskus ◽

Harriët Heijboer ◽

Bart J. Biemond ◽

...

Keyword(s):

Sickle Cell Disease ◽

The Netherlands ◽

Sickle Cell ◽

Neonatal Screening ◽

Causes Of Death ◽

Cell Disease

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Etiology of and Associations with Early Death in Adult Patients with Sickle Cell Disease At a Single Referral Institution.

Blood ◽

10.1182/blood.v120.21.2117.2117 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2117-2117

Author(s):

Courtney Fitzhugh ◽

Darlene Allen ◽

Wynona Coles ◽

Cassie Seamon ◽

Xiongce Zhao ◽

...

Keyword(s):

Sickle Cell Disease ◽

Cause Of Death ◽

Sickle Cell ◽

Causes Of Death ◽

Conflicts Of Interest ◽

Organ Damage ◽

Death Certificates ◽

Cell Disease ◽

Organ Function ◽

Significant Difference

Abstract Abstract 2117 Sickle cell disease (SCD) causes significant morbidity and early mortality. The largest study to date reported in 1994 a median survival of 42 years for men and 48 years for women with homozygous SCD1. One third died during a vaso-occlusive crisis, and 18% died of acute organ failure. Circumstances of death were unknown in 18% of patients. With improved patient care in the current era including hydroxyurea (HU) therapy, we sought to identify age and causes of death and associated clinical variables in adults with SCD at a single referral institution. We first reviewed death certificates and assigned one or more causes of death based on all listed data. We studied autopsy reports and medical records and communicated with medical providers when available to identify further causes of death. We then performed a cross sectional analysis of clinical features obtained at initial enrollment and compared those variables in patients who are now living versus deceased using univariate t-test or Chi-squared analysis in order to determine which factors may be associated with death. 528 patients with SCD evaluated at the National Institutes of Health between 2001 and 2010 were included. Out of 511 patients with known genotypes, 391 patients had homozygous SCD. 85 of 528 (16%) died at a median age of 43 years for men and 44 years for women. Death certificates were available for 55 (65%) patients. SCD and infection were the most common listed cause of death (12% each), followed by pulmonary hypertension and/or cor pulmonale (9%), cardiac etiology (8%), narcotic toxicity (7%), and other (31%). Cause of death was unavailable in 18 (21%) cases. Deceased patients were significantly older at the time of first enrollment compared to living patients (41.5 vs. 34.1 years, p<0.0001). There was no significant gender difference between groups. There was also no significant difference in the reported use of HU or fetal hemoglobin levels. Enrollment laboratories suggesting renal insufficiency in deceased patients included a higher creatinine, phosphorus, and uric acid (p<0.02). Hepatic dysfunction was also more prevalent in the deceased group as evidenced by significantly higher direct bilirubin and alkaline phosphatase and lower albumin (p<0.005). There was no difference in alanine transaminase levels. Lactate dehydrogenase (LDH) was significantly higher in deceased patients (p=0.01). As there was no significant difference in hemoglobin, indirect bilirubin, or absolute reticulocyte counts between groups, higher LDH in deceased patients suggests a non-erythrocytic source. Ferritin levels and percent saturation of transferrin were significantly higher and transferrin significantly lower (p<0.004) suggesting more iron overload in deceased patients. Lastly, brain natriuretic peptide levels (reported only in patients with creatinine <1mg/dL) and tricuspid regurgitant velocity were also significantly increased (p<0.0001), suggesting higher prevalence of cardiopulmonary disease in deceased patients. In summary, the most common listed cause of death was nonspecific and unrevealing, reported as SCD. Surprisingly, another common cause of death was infection. This may be due to the combination of poor organ function reserve and functional asplenia. Deceased subjects were older and more likely to have organ impairment at initial evaluation. These data suggest that while contemporary management of patients with SCD may decrease acute manifestations, end organ damage still occurs. Lastly, markers of organ function should be closely monitored as patients increase in age, and organ-specific and definitive disease-specific therapy should be considered before irreversible organ damage ensues. 1 Platt OS et al. NEJM, 1994. 330(23): 1639–1644. Disclosures: No relevant conflicts of interest to declare.

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Mortality and Causes of Death in Children with Sickle Cell Disease in the Netherlands.

Blood ◽

10.1182/blood.v114.22.1519.1519 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1519-1519

Author(s):

Evelyn M. van der Plas ◽

Xandra W. van den Tweel ◽

Harriët Heijboer ◽

Ronald B. Geskus ◽

B. J. Biemond ◽

...

Keyword(s):

Sickle Cell Disease ◽

Mortality Rate ◽

The Netherlands ◽

Sickle Cell ◽

Neonatal Screening ◽

Causes Of Death ◽

Screening Program ◽

Similar Proportion ◽

Cell Disease ◽

The Usa

Abstract Abstract 1519 Poster Board I-542 Introduction Despite the increasing incidence of sickle cell disease (SCD) in the Netherlands, mortality among this patient group has never been investigated. Studies on mortality in patients with SCD from the USA demonstrated that survival at the age of 20 years has improved from 79% for those born before 1975 to 89% in patients born after 1975. A recent study in the USA (2004) reflects the benefits of modern comprehensive care for SCD patients as survival increased to 94% by 18 years of age. The aim of this study was to collect information on the mortality rate and causes of death of children with SCD living in the Netherlands that were born before nationwide neonatal screening was implemented in 2007. This information is essential to provide a baseline for monitoring the effect of health care interventions, such as the introduction of nationwide neonatal screening. Causes of death may provide insight in areas where further improvement in the healthcare for SCD patients should be implemented. Patients and Methods All patients that were diagnosed with sickle cell disease (HbSS, HBSC, HbS-beta0, HbS-beta+) before the age of 18 years at the laboratory of the Academic Medical Center (AMC) in Amsterdam in 1985-2006 were included in the study. The AMC is one of the two large comprehensive care centers in the Netherlands, providing care to 30-40% of all Dutch SCD patients. Patients were followed from the time point of diagnosis onwards. Vital status at the end of study was determined by the last hospital visit or personal contact between January 2007 and March 2008. The causes of death were derived from hospital records. Survival estimates were obtained using the Kaplan-Meier estimator. Results In this time period we identified 298 pediatric patients with SCD. Homozygous sickle cell disease (HbSS) was present in 189 (63%) patients. The total time of follow-up was 2621 patient years. Twenty four patients (8%) were lost to follow up. The median age of the patients at the end of the observation period was 14.5 years (IQR 8.7-21.0 years). Twelve patients had died and all deaths were SCD related. Stroke (3 patients; 25%) and sepsis/meningitis (3 patients; 25%) were the most common causes of death. Four children (33%) died under 3 years of age. In two of them, death coincided or occurred shortly after the diagnosis of SCD. Three patients (25%) were between 3-18 years and 5 patients (42%) were older than 18 years at the time of death. A similar proportion of patients with the HbSS and HbSC genotype died (respectively 4.2% (95% CI: 1.9-7.9%) and 4.2% (95% CI: 1.0-10.8%)). The overall mortality rate was 0.46 deaths (95% CI: 0.25-0.77) per 100 patient years. The estimated survival rate of children with SCD at the age of three years was 93% (95% CI: 87-100%). At the age of 18 the survival was 91% (95% CI: 84 -99%). Discussion The fact that a similar proportion of patients with the HbSS and HbSC genotype died is striking, as HbSC generally has a milder phenotype than HbSS. In the absence of a neonatal screening program, early death from severe infection may have contributed to a relatively high mortality in HbSC patients. Although the estimated survival at the age of 18 years is comparable to recent findings in a neonatally screened cohort from the USA, the mortality rate of 0.46 deaths per 100 patient years is high in comparison to the mortality rate of 0.13 per 100 patient years in an East London cohort of SCD patients. This may partly be explained by a younger age of this East London cohort (median 7.8 years). However, the benefits of a longer standing neonatal screening program within the UK is likely to contribute to the low mortality rate in the East London cohort as well.Conclusions: In children with SCD living in the Netherlands, born before nationwide neonatal screening was implemented in 2007, 91% survives until the age of 18. Infection and stroke are the most common causes of death. Further study of children with SCD born after 2007, when neonatal screening was implemented, will elucidate whether neonatal screening for SCD has improved survival in these patients. Disclosures No relevant conflicts of interest to declare.

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