Sickle cell disease in Sri Lanka: clinical and molecular basis and the unanswered questions about disease severity

Abstract

Background: Though case reports and limited case series of Sickle cell disease in Sri Lanka have been reported previously, no attempt has been made hitherto to undertake a comprehensive genotypic-phenotypic analysis of this "rare" group of patients. Results: All accessible Sickle cell disease patients, totaling 60, including, 51 Sickle β-thalassaemia and 9 homozygous sickle patients were enrolled from seven thalassaemia treatment centres between December 2016-March 2019. The majority of patients were of Sinhalese ethnicity (n = 52, 86.67%). Geographically, two prominent clusters were identified and the distribution of Sickle haemoglobin in the island contrasted markedly with the other haemoglobinopathies. 3/ 9 homozygous sickle patients and 3/ 51 Sickle β-thalassaemia patients were receiving regular transfusion. Joint pain was the commonest clinical symptom among all sickle cell disease patients (n = 39, 65.0%). Dactylitis was significantly more common in homozygous sickle patients compared with the Sickle β-thalassaemia groups (p 0.027). Two genetic backgrounds sickle mutation were identified namely, Arab Indian and Benin. Among the regulators of Foetal hemoglobin in Sickle patients of the present study rs1427407 G > T seemed to be the most prominent modifier, with a significant association with Foetal haemoglobin levels (p 0.04). Conclusions: Overall, the clinical course of the Asian version of Sickle cell disease in Sri Lanka appears to be milder than that described in India.

Hydroxyurea and blood transfusion therapy for Sickle cell disease in South Asia: inconsistent treatment of a neglected disease

“…Projected requirement of blood in 2026 was 9.24 million units Widespread efficient and effective preventive strategies are urgently required to cope with the sharply increasing demand of blood Jain et al [ 59 ] A prospective cohort comparison study involving Hb SS patients from Nagpur, India 26 (33%) Hb SS patients received 74 transfusions (mean 2.8 episodes/patient) Pre-transfusion Hb was below 6 g/dl in 67% of patients. Only 4 out of 103 Hb SS patients were treated with HU Usage of HU was surprisingly lower among Hb SS patients from Nagpur cohort Darshana et al [ 21 ] A descriptive cross-sectional study involving patients with SCD from Sri Lanka 33% (3) of Hb SS patients and 5.9% (3) Hb S-β thalassaemia patients were on regular transfusions (> 8 transfusions/year). 26 (43.3%) patients were on HU therapy Usage of HU was not consistent and the practice of transfusions was very variable among Sri Lankan patients with SCD Barma et al [ 60 ] A prospective cohort study involving SCD children from Odisha, India HU treatment significantly reduced the requirement of blood transfusion (5.4 U/Y to 2.4 U/Y and VOC ( p < 0.001).…”

“…Moreover, the usage of HU for infants and children age 9 months or older who are asymptomatic or having infrequent pain episode has not adequately analysed among Indian patients. Therapeutic usage of HU for SCD have also been noted in couple of case reports from Pakistan, Bangladesh, Nepal and one descriptive cross-sectional study from Sri Lanka [21,22,26,28]. However, particulars of different dosing regimens in practice, toxicities and detailed response to HU therapy is largely unknown.…”

“…In their recent review Jain and Mohanty described that the poor compliance with HU among Indian patients may be due to physician’s concerns of potential long-term mutagenic effects and lack of familiarity of primary attending medical staff with HU therapy [ 54 ]. Inconsistency in adherence with HU therapy owing to the lack of familiarity of primary care medical staff has also been noted in a recent Sri Lankan study in which authors recommended the development of national guidelines for management of patients with SCD [ 21 ]. Socio-economic status and the financial capabilities of the sickle patients largely influence the affordability of standard care including HU in economically disadvantaged settings in the Indian sub-continent.…”

“…A study from Gujarat reported numerous transfusions for sickle patients with no clear diagnosis and justification [ 36 ]. Discrepancies and inconsistencies in transfusion practice for SCD has also been noted in Sri Lanka in which authors highlighted the disadvantage of not having a clear guideline [ 21 ]. Demand of blood for SCD transfusions is increasing in India by 0.99 million units per year.…”

“…Preliminary literature assessment suggested that the management of SCD in South Asian countries appears to vary and is not consistent with the generally practiced guidelines for SCD [ 20 , 21 ]. We decided to conduct this review on the two main modalities of SCD treatment, namely blood transfusion and HU therapy across the different countries in South Asia to see how its applied in this region.…”