PB2212: VARIANT HAEMOGLOBIN ASSESSMENT AND CORRELATION WITH PHENOTYPIC PRESENTATION AT DIAGNOSIS IN SICKLE CELL DISEASE: A SINGLE CENTRE RETROSPECTIVE ANALYSIS OF CENTRAL GUJARAT COHORT

Abstract

Background: Sickle cell disease (SCD) is caused by heritable point mutation at codon 6 of the human beta-globin gene widely distributed around the world. According to 2011 census, in India, there is a large tribal community of about 180 million. Among them18 million people carry the sickle cell trait and ~140,000 suffer from SCD. Gujarat State of India has a population of about 62 million, there are ~8.9 million tribal populations, among whom ~9, 00,000 people with Sickle cell Trait and ~70,000 people with SCD are expected. Though phenotypic heterogeneity of SCD is well known across the India, there is limited data on phenotypic presentation with variant haemoglobin correlation on large cohort from Central Gujarat. Aims: To correlate variant haemoglobin pattern with phenotypic presentation at diagnosis in SCD. Identify laboratory and clinical parameters to predict risk of complications in SCD. Methods: Five Hundred and seventy three patients registered at Haemato Oncology Care Centre (HOCC), Vadodara, Gujarat between August 2012 to December 2021, and diagnosed to have SCD were included in this study. This cohort represents tribal belt covering Bharuch,Narmada,Vadodara,Panchmahal,Dahod,Sabarkantha and Banaskantha districts of Central Gujarat. Diagnosis was based on clinical profile, complete blood counts (CBC) and peripheral smear evaluation along with variant haemoglobin assessment by High Performance Liquid chromatography / Capillary electrophoresis. Relevant Biochemistry investigations were done along with radiological assessment of hip joints in patients with specific symptoms.Osteonecrosis of Femur head (ONFH) was diagnosed according to Ficat and Arlet classification for ONFH. Recurrent Vaso occlusive episode(R-VOE) was labelled if there are >3 VOE/yr. Occasional VOE (O-VOE) labelled if <3 VOE/yr.Blood transfusion dependency was labelled if > 3 transfusion /yr required to maintain HB > 7 gm%.Splenomegaly was noted as palpable spleen below costal margin. Results: A total 573 SCD patients were evaluated. The median age was 20 years (range: 1-74) with 328 (57%) males and 245 (43%) females.HB was < 10 gm% in 378 (66%),HB <7 gm% in 78(14%),between7gm% to 10 gm% in 300(52.4%).315/378 (83%) had HBA <5%,Only 5/378 (1.32%)had Ferritin <20ng/ml.None had high indirect bilirubin with low HB. Transfusion dependency was found in 28(5%),HBA was 0%,<5%,6 to 10%,>10% in 12/28 (43%),7/28 (25%),6/28(21%),3/28(11%) respectively. R-VOE observed in 207 (36%),O-VOE in 259(45%),No VOE in 107(19%).Splenomegaly was found in 268(47%).HBF <10% in 86 (15%),10 to 20% in 258(45%)>20% in 229(40%).All Patients with no VOE 107(19%) had HBF >10% with palpable splenomegaly.ONFH was diagnosed on imaging in 108 (19%).101/108(93.5%) had HBF >10%.,25/108 (23%)had palpable splenomegaly. Summary/Conclusion: In our cohort High HBF with Splenomegaly was associated with no VOE. No protection for ONFH seen with high HBF or palpable spleen Regional increased prevalence of coinheritance of Thalassemia in SCD play important role in influencing clinical presentation and progression of complication like transfusion dependency and ONFH. In LMIC, Variant haemoglobin assessment with CBC, Retic count values can be used to predict probable coinheritance of Thalassemia; however DNA Mutation analysis on larger cohort can be done for validation. Region specific risk adapted optimization of treatment can modify natural history of disease