PB1402 - Evaluate the role of Factor V Leiden G1691A, Prothrombin G20210A and MTHFR C677T polymorphism on Indian sickle cell disease patients: A tertiary care experience

Tuesday, June 25, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

HP

HARERAM PANDEY

Post doctoral fellow
All India Institutes of Medical Science New Delhi
NEW DELHI, Delhi, India

Co-Author(s)

Ravi Ranjan, MSc PhD

Scientist
All India Institute of Medical Sciences
New Delhi, Delhi, India
JD

Jasmita Dass, MD, DM

Associate Professor of Hematopathology
All India Institute of Medical Sciences, New Delhi
New Delhi, Delhi, India
MA

Mukul Aggarwal

Assistant Professor
All India Institute of Medical Sciences, New Delhi
Delhi, Delhi, India
GV

Ganesh Kumar Viswanathan

Associate Professor
All India Institute of Medical Sciences, New Delhi
New Delhi, Delhi, India
rD

rishi Dhawan

Assistant professor
All India Institutes of Medical Science,new delhi
Delhi, Delhi, India
PK

Pradeep Kumar

Associate Professor
All India Institute of Medical Sciences, New Delhi
New Delhi, Delhi, India
TS

Tulika Seth

Professor
All India Institute of Medical Sciences, New Delhi
New Delhi, Delhi, India
MM

Manoranjan Mahapatra

Professor and Head
All India institute of Medical Sciences, New Delhi
New Delhi, Delhi, India

Background: It is well known that sickle cell disease (SCD) patients show activation of blood coagulation, fibrinolytic system and increased platelet activity during vaso-occlusive crises. A number of genetic polymorphisms associated with thrombophilia have been studied as potential genetic modifiers of SCD.

Aims: Investigate the role of thrombotic gene polymorphism in the development of vascular complications in SCD.

Methods: This study involved 65 sickle cell anaemia (Hb SS) patients and 70 healthy controls. Five mille litres of venous blood were collected after obtaining the signed informed consent form. Study was approved by the institutional ethic committee. Total genomic DNA was isolated from peripheral blood leukocytes by the kit (Bioserve) method. All three mutations; V Leiden, prothrombin, and MTHFR were screened by PCR RFLP methods using endonuclease MnlI, Hind III, and Hinf I, respectively. Statistical analysis was performed using GraphPad statistics software. P Values < 0.05 were considered significant.

Results: The mean age of SCD patients was 15.4 (±7.3SD) years and 18.5 (±5.8SD) years for controls. The prevalence of MTHFR heterozygous variant (C/T) and homozygous variant (T/T) was 27.3% and 13.5% respectively. The incidence of factor V Leiden heterozygous (G/A) was 14% but no homozygous mutants (A/A) was found in patients as well as in controls. The carrier prevalence of MTHFR and FVL was found significantly high in patients than controls (C/T; p= < 0.0001, OR 3.9, 95% CI 1.9-8.0, G/A; p= < 0.0001, OR 51.9, 95% CI 3.13-876.0). Prothrombin G20210A mutation was absent in all subjects. Patients with mutant variants of MTHFR and FVL had higher frequencies of joint pain, splenomegaly, chest pain, fever, frequent blood transfusion and early manifestation of clinical symptoms.

Conclusion(s): Our findings suggest that MTHFR and factor V Leiden polymorphism pose risk factor for vascular complications in Indian SCD.