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Evaluation of role of FV, FVIII and APLAs in the pathogenesis of APCR in FV Leiden negative DVT patients: a study in India

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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.

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Acknowledgements

Authors would like to thank Indian Council of Medical Research (ICMR) for providing funds in the lab and Senior Research Fellowship to AS.

Author contributions

RS was the principal investigator of the work. AS designed the study, performed experimental studies, compiled the data, and contributed to writing. KS reviewed the manuscript, contributed to writing and provide valuable clinical input. AB and RR drafted the manuscript. KK, RK, HRP and VKK helped in shaping the manuscript. All the authors read and approved the final manuscript.

Funding

The study was funded by Indian council of Medical Research (ICMR).

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Authors and Affiliations

  1. Department of Haematology, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India

    Amit Sharma, Ravi Ranjan, Kamal Kishor, Ravi Kumar, Hareram Pandey & Renu Saxena

  2. Institute of Naval Medicine (INHS) Asvini, Mumbai, 400005, India

    Kanwaljeet Singh

  3. Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany

    Arijit Biswas

  4. Department of Biostatistics, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India

    Vineet Kumar Kamal

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  1. Amit Sharma
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  2. Kanwaljeet Singh
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  3. Arijit Biswas
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  4. Ravi Ranjan
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  5. Kamal Kishor
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  6. Ravi Kumar
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  7. Hareram Pandey
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  8. Vineet Kumar Kamal
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  9. Renu Saxena
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Correspondence to Renu Saxena.

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Research involving human rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institute Ethics Committee of All India Institute of Medical Sciences, New Delhi, India.

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Informed consent was obtained from all individual participants included in the study.

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Sharma, A., Singh, K., Biswas, A. et al. Evaluation of role of FV, FVIII and APLAs in the pathogenesis of APCR in FV Leiden negative DVT patients: a study in India. J Thromb Thrombolysis 43, 217–223 (2017). https://doi.org/10.1007/s11239-016-1469-6

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  • DOI: https://doi.org/10.1007/s11239-016-1469-6

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