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71 Survival in Sickle Cell Disease: Data from a Well-Resourced, National Health System Setting

Hemoglobinopathies, Excluding Thalassemia – Clinical
Program: Oral and Poster Abstracts
Type: Oral
Session: 114. Hemoglobinopathies, Excluding Thalassemia – Clinical: Novel Insights into Pathophysiology in Sickle Cell Disease
Saturday, December 5, 2015: 1:00 PM
W340, Level 3 (Orange County Convention Center)

Kate Gardner, MA MBBS MRCP1,2, Abdel Douiri, PhD3*, Marlene Allman2*, Emma Drasar, MBBS, PhD, MRCP, FRCPath1,2*, Moji Awogbade1 and Swee Lay Thein, MD, DSc2,4

1Department of Haematology, King's College Hospital, London, United Kingdom
2Molecular Haematology, Division of Cancer Studies, King's College London, London, United Kingdom
3Primary Care and Public Health Sciences, King's College London, London, United Kingdom
4National Heart, Lung and Blood Institute, Sickle Cell Branch, National Institutes of Health, Bethesda, MD

Background: In well-resourced countries, early mortality in sickle cell disease (SCD) is no longer a major feature, thus the burden of SCD mortality has shifted to adults. Recent data on patients with SCD in USA confirmed continuing improvement in adult survival, attributed to better preventative care. Health economics may play a key role in clinical outcome in SCD; we hypothesise that survival would be longer in a system which is not insurance based. King's College Hospital, London, UK has a large SCD cohort in a well-resourced setting within a national health service framework.

Methods: 712 adult (≥18 years) SCD patients were observed over 10 years (2004-13 inclusive) to identify mortality outcome (total 5268 patient-years of observation with median 8 years of observation per patient, over median 9 total hospital visits). Demographic data, sickle and alpha genotype were documented. Laboratory data were also collected (list in table): outpatient laboratory values were averaged over the 10 year period to create a “steady state” value for each patient. Mean number of hospital admissions with a sickle pain crisis was calculated (total admissions/number of observed years per patient).

IBM SPSS Statistics 22 was used for Kaplan Meier survival analysis and then regression analysis was undertaken, based on the Cox proportional hazards model, to identify variables which were associated with mortality, and produce hazard ratios for putative predictors (demographic, laboratory and admission data).

Results: 43 patients (6.0%) died during the study at a median age of 42 years (IQR: 31-48). Kaplan Meier analysis showed an estimated median survival of 77 years (95% CI: 68-85) for all sickle genotypes. Sub-analysis by sickle genotype showed: HbSS/HbSβ0 thalassaemia together (33 deaths in 450 patients) with estimated median survival 67 years; and HbSC (8 deaths in 229 patients) with significantly higher estimated median survival 82 years (p<0.001), see figure 1. For both genotypes, there was no gender difference on sub-analysis. For HbSS/HbSβ0, there was a significant difference by hospitalisation rate with survival: median survival in those with ≤0.5 admissions/year was 67 years, significantly higher than 60 years (CI: 43-77) for high admission rates (p=0.001), see figure 2.

Cox regression analysis was conducted for HbSS/HbSβ0 patients (demographic, laboratory and admission data), see table. Risk of death is increased: 2.5-fold if ferritin is high (>1000ug/L), 6% for every extra 10umol/L total bilirubin, 20% for every extra 100 IU/L LDH, 18% for every extra 1 x109/L WBC (all steady state values). Hospitalisation rates were analysed two ways: using the continuous variable, risk of death is increased by 37% for every admission accrued in an individual's mean admission/year statistic; and using a dichotomous variable (high versus low admissions), those with high admission rates have a hazard ratio over 3-fold that of those with low admission rates.

Conclusions: These data indicate that adult survival in SCD in our institution is high; estimated median survival of 67 years for HbSS/Sβ0 and 82 years for HbSC. This is markedly longer than those recently quoted from the USA, which may be due to disparities in health economics. Cox regression sub-analysis for the HbSS/Sβ0 group reveals multiple “predictors” of increased mortality risk including classical laboratory markers of SCD severity - iron loading (likely correlated with disease severity via transfusion rate), inflammatory and haemolytic parameters - as well as confirming hospitalisation rate as a simple but strong predictor of survival in SCD.

Table: Cox regression analysis for HbSS/HbSβ0 thalassaemia


HbSS/HbSβ0 thalassaemia

(n=450, 33 deaths)

Hazard ratio (CI)

p value


Alpha Thalassaemia*

1.342 (0.666-2.706)


Sex* (M=default)

0.674 (0.339-1.340)



Total bilirubin umol/L

1.006 (1.004-1.008)


C-reactive protein (CRP) mg/L

1.019 (0.998-1.042)


High Ferritin >1000ug/L*

2.518 (1.212-5.232)


Lactate dehydrogenase (LDH) IU/L

1.002 (1.000-1.004)


WBC x109/L

1.181 (1.037-1.345)


Hb g/L

0.979 (0.956-1.002)


Reticulocytes x109/L

1.002 (0.999-1.005)



Mean number admissions / year

1.374 (1.159-1.630)


High admission rate (>0.5/year)

3.131 (1.567-6.259)


*Dichotomous variables

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH