A descriptive study of the characteristics of older adults with sickle cell disease
Authors: Anjum B. Khan, Rachel Kesse‐Adu, Cormac Breen, Patrick B. Murphy, John Chambers, Paul Holmes, Joanna Howard
Journal: American Journal of Hematology (2017)

Life expectancy in patients with sickle cell disease (SCD) has been steadily improving over the last 30 years. There are little published data on the clinical outcomes in older patients with SCD, although previous series have suggested decreasing hemoglobin and worsening renal function with increasing age.1, 2 We identified 204 patients with SCD aged ≥40 years on July 1, 2013. Patient data were extracted from electronic patient records and analyzed to describe clinical phenotype and rates of chronic disease. A significant positive skewing of the age distribution seen in both HbSS and HbSC patients was more marked in the HbSS cohort (median age 46 vs. 50 in the HbSC cohort, P < .001). Only 10% of our cohort were ≥60 years (7% HbSS, 16% HbSC). 26% HbSS and 12.5% HbSC patients had experienced a severe vaso-occlusive crisis (VOC) requiring hospital admission within the previous two years (range 1–7), suggesting admission rates for patients >40 are low compared with younger SCD patients. This is in keeping with other studies and may reflect experience in self-management and/or a survival advantage for patients with a milder phenotype. Patients with HbSS had significantly lower hemoglobin and higher bilirubin, LDH, reticulocyte values compared with HbSC patients. White cell, platelet counts, ferritin, HbF, and red cell alloimmunization levels were higher in HbSS patients (see Table 1). In contrast to previous studies, we saw no correlation between age and hematopoietic reserve as a continuous variable or on comparison of 2 discrete cohorts (age 40–45 vs. ≥50 years) and found no changes with age in markers of hemolysis or HbF levels. Reticulocyte counts and LDH were reduced in HbSS patients over 60 versus age 40–49, consistent with less severe phenotypes in the elderly. The effect of age on hemoglobin requires longitudinal investigation. Increasing age was strongly correlated with hypertension and declining renal function for both HbSS and HbSC patients (Spearman's rho 0.23 and 0.30, respectively, see Table 1). The decline in eGFR persisted when controlling for systolic blood pressure, supporting previous studies.1 21% (25/117) of HbSS and only 1% (1/88) HbSC were proteinuric (urine PCR > 50 mg/mmol). There was no evidence of increasing proteinuria with age although this has been previously described.3 Our results confirm a high prevalence of vitamin D deficiency in adults with SCD and Vitamin D levels are significantly lower in older HbSS adults compared with HbSC (see Table 1, P = .015). Recent studies suggest that children's pain scores improve with high-dose supplementation and this approach merits exploration in older adults, particularly those with levels below 30 nmol/L who are at risk of chronic bone and cardiovascular pathology.4 Pulmonary function testing showed that almost all patients had normal FEV1/FVC ratios, however 79% of HbSS and 83% of HbSC patients had impaired transfer factors of which 45% of HbSS and 29.7% of HbSC showed moderate to severe reductions (<60%). Of 29 patients (25 HbSS) who underwent overnight sleep studies for assessment of obstructive sleep apnoea (OSA) and nocturnal hypoxia, 3 HbSS patients had OSA (4% oxygen desaturation index ≥ 10), 2 patients fitted criteria for nocturnal hypoxia (SpO2 <90% for >30% of total sleep time) and 4 patients had evidence of both. Two HbSC patients had evidence of OSA. A subset of 46 HbSS and 32 HbSC patients underwent MRI/MRA brain imaging for investigation of neurological symptoms. The majority (70%, 32/46) of HbSS patients had abnormalities including ectatic or narrowed arteries with small aneurysms, small vessel ischemic change, border zone ischemia and large infarcts, while only 44% (14/32) of HbSC exhibited these changes (P = .023). There was a significant association between MRI changes and age for HbSC patients (HR = 10.4 for age > 50 vs. <50, P = .04). At this time, all patients in our service were being offered routine echocardiography. Older HbSS patients were significantly more likely to have dilatation of both left and right atrial chambers than HbSC although left ventricular dimensions and ejection fraction were similar. Left atrial diameter correlated with increasing age in HbSC patients. Of those patients in whom peak tricuspid regurgitant jet velocity (TRVmax) was present or measurable, TRVmax was ≥2.5m/s in 11/36 (31%) HbSS and 3/13 (23%) HbSC patients. Two patients in both groups had a TRVmax ≥ 2.9 m/s. Eight patients with HbSS and seven with HbSC had additional markers of pulmonary hypertension such as reduced pulmonary artery acceleration time, tricuspid annular plane systolic excursion or tissue Doppler imaging systolic myocardial velocity (TDI S').5 Twenty-one percent of HbSS patients over 40 had been prescribed hydroxycarbamide compared with only 3% of HbSC patients, and age did not affect likelihood of receiving hydroxycarbamide. Prior deleterious patient phenotype was reflected in higher peak urine PCRs (87 vs. 41), ferritin levels (312 vs. 124), and proportions of alloimmunised patients (38% vs. 15%) or those receiving renin-angiotensin axis inhibitors (42% vs. 13%). Relatively small numbers of patients receiving hydroxycarbamide, despite the association with reduced mortality, indicate the importance of exploring current barriers to use. 15% (17/116) of HbSS and 1% (1/88) of HbSC patients were receiving regular transfusion therapy. Our data are limited by very few patients aged over 60 years and although we did see disease correlations with increasing age longitudinal trends cannot be inferred from a cross-sectional study. This work provides detailed baseline population data to inform future trial design. As the SCD population ages it is essential we gain a more robust understanding of the older SCD clinical phenotype. This will allow us, and our patients, to make more informed decisions about disease-modifying or newer experimental therapies. We echo previous calls for a national database and longitudinal studies with systematic prospective data collection to enable us to understand the magnitude of age-related comorbidities and to predict long-term outcomes.6 Previous authors have noted that sickle patients are often not managed for medical comorbidities and were not up-to-date on age-appropriate health screening.6 Clear evidence-based guidelines aimed at primary and secondary health care professionals would assist in this goal and would be aided by further research into interventions and outcomes in this older age group. The authors declare that there is no conflict of interest regarding the publication of this article.