Screening for Multiple Organ Damage in Indian Sickle Cell Disease Cohort- a Step Towards Comprehensive Care
Authors: Shinde Nikhil Sharad , Nadkarni Anita HARISH , Madkaikar Manisha R , Gupta Kalpna , Kamble Amit , Rajurkar Sourabh B , Pophali Snehal ANIL , Umare Vinod DHANRAJ 
Published: December 2023

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) &gt;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.