Clinical Phenotypes in a Cohort of Nigerian Patients with Sickle Cell Anaemia: Relationship to Serum Lactate Dehydrogenase

Abstract

Background: Distinct  phenotypes  based  on  serum  lactate dehydrogenase (LDH) levels have been described  in  sickle  cell  anaemia  (SCA)  in studies mainly conducted in high-income countries. We aimed to characterise the phenotypes  of  Nigerian  patients  with  SCA based  on  serum  LDH  distribution  and  pain episodes.

Materials and Methods: This was a descriptive cross-sectional study of 200 male and female patients with SCA, aged 2-43  years,  who  were  in  the  steady-state. Medical history was obtained through structured questionnaire and review of clinical notes. Haematological and biochemical investigations included full blood count, reticulocyte count, Hb F quantification, serum LDH and total and direct bilirubin. Data were analysed using Stata v15. Patients were categorised into phenotypes based on quartile distribution  of  LDH  and  annual  pain  rates. Subgroup analyses were conducted within the upper and lower quartile groups to elucidate their subtle characteristics.

Results: There was moderate, but significant correlation  between  serum  LDH  and  other haemolytic  markers.  The  mean  haematocrit, Hb F level, total white blood cell, platelet and reticulocyte counts were statistically different between  the  upper  and  lower  LDH  quartiles (p<0.05), while the annual pain rates were not different (p=0.1117). Within the upper quartile of LDH distribution (i.e. hyperhaemolysis group, n=52), 11(5.5%) had concomitant high pain rate (painful events ≥ 3/annum) suggestive of a mixed haemolytic/ vasoocclusive phenotype. Similarly, within the lower quartile (viscosity/vasooclussive group, n=50), 47(23.5%) had associated low pain rate (painful  events  <  3/annum)  suggestive  of  a clinically silent phenotype. Patients with LDH levels in the interquartile range had pain rate ranging from high to low, suggesting a variable phenotype.

Conclusions: Clinical  phenotypes  of  patients  with  SCA  in Northern Nigeria are potentially more complex than those described outside the African setting. A 'Venn diagram' model is proposed to depict these phenotypes.