IDENTIFICATION AND CHARACTERISATION OF FACTOR V LEIDEN MUTATION IN PREGNANT WOMEN IN SOUTHWESTERN NIGERIA.

ABSTRACT

Factor V Leiden (FV_Leiden) is an hereditary coagulation disorder which results in activated protein C (APC) resistance in the regulation of the coagulation cascade. It is characterized by a poor anticoagulant response to activated protein C (APC) with an increased risk for venous thromboembolism (VTE) and found in 5% Caucasian and about 1.2% African-American. Manifestation of factor V Leiden mutation in thrombotic disorder often require the presence of risk factors such as malignancy, pregnancy, trauma, surgery, the use of oral contraceptives, the presence of an antiphospholipid antibody. This study aimed to identify and characterize the Factor V_Leiden mutation in pregnant women in southwestern Nigeria. Four hundred and fifty (450) subjects comprising three hundred pregnant (300) and one hundred and fifty (150), apparently healthy, non-pregnant women who served as controls were recruited, across the six states of southwestern Nigeria, for this study. The parameters assessed include packed cell volume (PCV); Platelet count (Mindray analyser); haemoglobin electrophoresis by alkaline electrophoresis; Prothrombin time (PT) and activated partial thromboplastin time (APTT) tests (Diagen Ltd); D-dimer (Tina Quant Gen II, Roche Cobas CII analyser) and Activated Protein C resistance assays (Chromogenix Coatest,Diapharma); and the real time Polymerase chain reaction (RT-PCR) analysis (Biorad CFX76 Real Time System). The results showed a significantly increased         D-dimer (0.87±1.00) in the subjects while other coagulation markers were significantly reduced (p<0.05). The prevalence of APC-V ratio <2.0 among the studied population is 1.1% (5 subjects) with 1.3 % among subjects and 0.7% among controls while the prevalence of FV_leiden mutation was estimated as 0.7% (3 subjects) among the studied population and the genes were analyzed and displayed as heterozygous pattern. These 3 subjects with the FV_leiden mutation were assessed to possess reduced PT (<11secs) and APTT (<25secs); increased D-dimer (>0.50ugFEU/ml); reduced APC-V ratio <2.0 and HbAS /HbAA and recurrent thrombosis associated symptoms. Also, it was observed that some subjects without APCr and FV_Leiden mutation possess reduced and increased levels of   PT/APTT and increased D-dimer simultaneously. This study concludes that APC resistance and FV_Leiden exist (0.7%) in its heterozygous state in this region with the manifestation observed in the assays. Furthermore, this study has revealed that the FV_Leiden mutation is not related or dependent on the haemoglobin genotype of an individual and revealed likelihood of detecting some other coagulation disorders that could result in maternal mortality.