Systematic Evaluation of Sickle Cell-Related Organ Damage and Complications: Implications for Sickle Cell Disease Management.
Authors: van Eduard J. Beers , Van Der Anna Giessen , Van Charlotte F.J. Tuijn , Schnog John-john , Biemond Bart J. 
Published: October 2019

Sickle cell disease (SCD) is characterised by acute complications such as the painful vaso-occlusive crisis, acute chest syndrome and stroke. Although these acute complications are well known and mostly easy recognised, the impact of sickle cell-related chronic end-organ damage on outcome may well be underappreciated. In fact, often SCD severity is assessed. by the frequency of acute vaso-occlusive crises. However, accumulating chronic organ damage (such as renal failure and pulmonary hypertension) is nowadays recognized as an important determinant of disease morbidity as well. The aim of this study is to evaluate the prevalence of sickle cell-related complications and organ damage and their relation to SCD genotype and to established laboratory parameters of SCD morbidity in a tertiary teaching hospital. Furthermore, relations between complications and different forms of organ damage will also be determined. Sickle cell patients were consecutively and systematically screened for manifestations of chronic organ damage and their history of complications related to SCD and/or SCD-related treatment was retrospectively studied from their medical records. Organ damage and the history of sickle cell-related complications were expressed as a cumulative disease morbidity score (DMS). Every form of organ damage or complication scores 1 point and is divided by the number of screened items resulting in a maximal DMS of 1. Correlations were analysed with the Chi-Square test. All adult sickle cell patients (HbSS, HbSβ and HbSC) were included in our study (n=99). Six patients were excluded from analysis because of incomplete data (less than 7 of the 12 items).

Prevalence of specific organ damage and complications Total HbSS HbSβ HbSC P value Numbers are percentages or medians (iqr). * Two-sided Chi-square tests **Two sided Kruskal-Wallis test N 93 49 16 28 Age (year) 28 (22–39) 27 (21–41) 35 (25–41) 28 (20–34) 0.324** Female (%) 65 62 56 71 0.567 Disease Morbidity Score 0.11 (0–0.25) 0.18 (0.09–0.33) 0.09 (0–0.19 0.10 (0–0.17 0.010** Organ damage/ complications (%) Microalbuminuria 22 33 0 15 0.063 Renal failure 10 15 0 7 0.201 Pulmonary hypertension 25 40 0 7 0.006 Retinopathy 41 28 30 65 0.016 Perceptive hearing loss 12 9 27 6 0.205 Iron overload 10 17 0 4 0.063 Cholelithiasis 51 66 43 27 0.009 Avascular osteonecrosis 12 17 13 4 0.242 Leg ulcers 5 11 0 0 0.089 Acute chest syndrome 24 31 25 11 0.128 Frequent vaso-occlusive crises (>2/yr) 14 17 19 4 0.374 Stroke 6 13 0 0 0.053

The DMS correlated significantly with c-reactive protein (R= 0.27, P=0.013), blood urea nitrogen (R=0.422, P>0.001) and hemoglobin (R= −0.326, P=0.003). No statistically significant correlation with leukocyte counts or HbF% was demonstrated. These data underscore the importance of systematic evaluation of all patients with SCD in the outpatient setting since many of the sickle cell-related complications may otherwise go unnoticed, thereby delaying the institution of potential therapeutic measures. Importantly, the lack of any significant association between the frequency of vaso-occlusive crises and manifest sickle cell-related organ damage illustrates its limited value as a marker of disease severity.