Screening for Multiple Organ Damage in Indian Sickle Cell Disease Cohort- a Step Towards Comprehensive Care

Introduction:

Sickle cell disease (SCD) is the most common hereditary monogenic disorder and is a major health burden in India. Meagre information is available on multiple organ damage among Indian SCD population. The present study attempts to understand the spectrum of organ damage in a group of Indian SCD cohorts.

Objectives:

• To investigate the spectrum of early organ dysfunction and chronic organ damage among SCD patients at different age groups.

• To study the association of haematological and biochemical parameters with organ dysfunction or chronic organ damage.

• To understand the implication of genetic modifies with clinical profiles of SCD patients.

Methodology:

• Clinical investigations of SCD individuals such as MRI of brain, ultrasonography of abdomen, spirometry of lung, 2 D echo of heart and ophthalmology.

• Laboratory investigations of SCD individuals such as haematological parameters by cell counter (Sysmax XP100), HbF & HbS fractionization by HPLC method (Biorad Variant 2), liver function test and kidney function test by automated biochemistry analyser (Roche Cobas C111).

• Co-inheritance of α-thalassemia and Xmn-1 polymorphism by multiplex PCR and PCR-RFLP respectively.

100 SCD individuals were recruited with informed consent by a consecutive sampling for the study at ICMR-Centre for Research Management and Control of Haemoglobinopathies (ICMR-CRMCH), Chandrapur. SCD individuals at non-crisis, steady state; with no blood transfusion history prior 3 months or not admitted in hospital for vaso-occlusive crisis prior 1 month were enrolled in the period Jan'2021-Jan'2022.

Result:

One hundred SCD individuals (44 males: 56 females) were enrolled. The median age of individuals was 18 years (Interquartile range (IQR): 13-29 years). Individuals were categorized into two groups based on their ages. Children and adolescents group (6-17 years): 46 individuals, and Adults (18-52 years): 54 individuals. Out of 100, 65 were drug hydroxyurea (HU) are on HU, while remaining 35 were not taking HU. The median dosage of at 11.9 mg/kg/day (IQR: 9.17-13.5 mg/kg/day).

The current study reports the spectrum of organ damage involving onset of organ dysfunction to end organ damage such as ischemia/sclerosis/atrophy 12/58 (20.7%) to stroke 2/58 (3.4%), mild restriction/obstruction 55/96 (57.3%) to mixed blockage lung disease 6/96 (6.2%), cholelithiasis 24/100 (24%) to chronic cholecystitis/cholecystectomy 6/100 (6%), shrunken spleen 16/100 (16%) to autosplenoctomy 24/100 (24%). No pulmonary hypertension determined by tricuspid valve regurgitation (TRV) >2.5 m/s was observed among 100 SCD individuals. No case of proliferative sickle retinopathy was detected in the cohort.

Laboratory investigations: The mean ± standard deviation (S.D.) hemoglobin and HbF% levels among 100 SCD individuals were found to be 9.7±1.6 gm/dl and 21.2±6.6% respectively. Hematological and biochemical parameters showed association with liver and splenic dysfunction. Four out of 76 (5.3%) individuals were tested positive for microalbuminuria. No individual showed higher levels of estimated glomerular filtration rate.

Molecular investigations: Ninety three HbS homozygous and 7 HbS-β thalassemia compound heterozygous were identified by ARMS-PCR method. The co-inheritance of α-gene mutations was observed in 45/94 (47.9%) SCD individuals, while the remaining 49/94 (52.3%) were normal. The Xmn1 polymorphism present in the Gγ globin promoter region -158 C→T (HBG2 c.-211 C→T) position, showed 88 as homozygous for mutant allele [+/+], while 12 as heterozygous[ +/-]. No association of α-thalassemia and Xmn1 polymorphism with organ dysfunction was observed.

Conclusion:

Though, vaso-occlusive crisis is the main clinical manifestation in SCD, sickle related organ damage is an important determinant for clinical severity of the disease. The progression of organ dysfunction/damage is evident as the age progresses. The comprehensive check-up at regular interval is required for the identification of early organ dysfunction and to prevent the chronic organ damage in SCD individuals.