title: Evaluation of role of FV, FVIII and APLAs in the pathogenesis of APCR in FV Leiden negative DVT patients: a study in India.
abstract: Resistance to APC (APCR) is a very important cause of thrombophilia and most frequently caused by the Leiden mutation. APCR is also seen in the absence of FV Leiden and associated with elevated levels of factor V (FV), factor VIII (FVIII) and antiphospholipid antibodies (APLAs). The aim of this prospective case control study was to find out the frequency and role of FV, FVIII and APLAs in the pathogenesis of APCR in FV Leiden negative deep vein thrombosis (DVT) patients in India. A total 30 APCR positive and FV Leiden negative patients with DVT and similar number of age and sex matched healthy controls were recruited. Significantly higher mean FVIII levels were observed in patients as compared to controls [patients: 132.3 ± 30.7 IU/ml, controls: 117.5 ± 17.7 IU/ml, p = 0.025]. A significant negative correlation was also observed between FVIII and APC ratio (Pearson correlation = 0.368, p = <0.001). Mean FV levels in patients [107.1 ± 13.1 IU/ml] and controls [102 ± 11.9 IU/ml] were not statistically significant (p = 0.119). Anti β2 glycoprotein I (Anti-β2-GPI, IgG) showed significant association with APCR phenotype (p = 0.050), unlike other factors such as protein C, protein S, lupus anticoagulant and anticardiolipin antibodies. The strong association of FVIII and anti-β2 GPI (IgG) antibodies with APCR phenotype is suggestive of incorporation of these factors in APCR positive DVT patients in the absence of FV Leiden mutation in India. However more studies in large sample size are required for setting up the proper investigation protocol in these patients.
authors.affiliation: Department of Haematology, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Institute of Naval Medicine (INHS) Asvini, Mumbai, 400005, India.
authors.forename: Kanwaljeet
authors.initials: K
authors.lastname: Singh
authors.affiliation: Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany.
authors.forename: Arijit
authors.initials: A
authors.lastname: Biswas
authors.affiliation: Department of Haematology, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India.
authors.forename: Ravi
authors.initials: R
authors.lastname: Ranjan
authors.affiliation: Department of Haematology, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India.
authors.forename: Kamal
authors.initials: K
authors.lastname: Kishor
authors.affiliation: Department of Haematology, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India.
authors.forename: Ravi
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Haematology, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India.
authors.forename: Hareram
authors.initials: H
authors.lastname: Pandey
authors.affiliation: Department of Biostatistics, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India.
authors.forename: Vineet Kumar
authors.initials: VK
authors.lastname: Kamal
authors.affiliation: Department of Haematology, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India. renusaxena@outlook.com.
authors.forename: Renu
authors.initials: R
authors.lastname: Saxena
mesh_terms: D020016:Activated Protein C Resistance / Q000209:etiology*; D000328:Adult; D017152:Antibodies, Antiphospholipid / Q000097:blood*; D016022:Case-Control Studies; D005165:Factor V / Q000032:analysis / Q000235:genetics*; D005169:Factor VIII / Q000032:analysis*; D005260:Female; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020246:Venous Thrombosis / Q000209:etiology*
chemical_list: D017152:Antibodies, Antiphospholipid; C095381:factor V Leiden; C078147:F8 protein, human; D005165:Factor V; D005169:Factor VIII
keywords: Activated protein C resistance; Antiphospholipid antibodies; Deep vein thrombosis; Factor VIII