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LETTER TO THE EDITOR
Year : 2013  |  Volume : 19  |  Issue : 3  |  Page : 377-378
 

Possible impact of factor V Leiden genotype on warfarin induced bleeding


Department of Thrombosis and Haemostasis, National Institute of Immunohaematology, KEM Hospital, Parel, Mumbai, Maharashtra, India

Date of Web Publication30-Oct-2013

Correspondence Address:
Shrimati Shetty
Department of Thrombosis and Haemostasis, National Institute of Immunohaematology, 13th Floor, KEM Hospital, Parel, Mumbai - 400 012, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-6866.120807

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How to cite this article:
Gaikwad T, Ghosh K, Shetty S. Possible impact of factor V Leiden genotype on warfarin induced bleeding. Indian J Hum Genet 2013;19:377-8

How to cite this URL:
Gaikwad T, Ghosh K, Shetty S. Possible impact of factor V Leiden genotype on warfarin induced bleeding. Indian J Hum Genet [serial online] 2013 [cited 2016 May 24];19:377-8. Available from: http://www.ijhg.com/text.asp?2013/19/3/377/120807


Sir,

We read with interest the report, recently published by Nahar et al. [1] on the prevalence of warfarin sensitive alleles in factor V Leiden (FVL) mutation carriers. The study provides preliminary evidence for the need of pre-prescription genotyping of warfarin sensitive polymorphisms (CYP2C9*2, *3 and Vitamin-K epoxide reductase complex subunit1 [VKORC1]-1639G/A) in patients who are at risk of thrombosis (carriers of thrombophilic marker) and require anticoagulation therapy.

The authors have reported that 55.6% of the patients who carry FVL mutation also carry warfarin sensitive genotypes; thus, it is important that all patients with thrombophilia need warfarin genotyping prior to prescription with warfarin. The prevalence of these genotypes are however, not significantly different in few other studies including ours [Table 1], where the allele frequencies were studied in warfarin anticoagulated patients, as well as normal healthy controls. [2],[3] FVL mutation has however, not been studied in these cases.
Table 1: Genotype and allele frequencies of CYP2C9 and VKORC1 in few studies from India

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In our study, which included 145 warfarin treated patients (blinded to FVL or other thrombophilic marker carrier status), nearly 44.14% patients were found to be carriers for one or more variant genotype(CYP2C9*2, *3 and VKORC1-1639G/A). Out of these warfarin sensitive genotype carrier patients, 67.18% patients faced over anticoagulation (INR > 4) while on warfarin. Indicating that genotyping of warfarin sensitive markers will be beneficial in all the patients prior to the initiation of anticoagulation therapy. [3]

Another important aspect of coinheritance of thrombophilia is its impact on the bleeding phenotype. Several studies, both in vitro and case series have shown that FVL mutation modulates the clinical severity in hemophilia and other rare bleeding disorders. [4],[5] We therefore premise that FVL carrier patients should be at lower risk of over anticoagulation than the FVL non-carrier patients. This would be confirmed by undertaking studies in large series of anticoagulated patients with the long duration follow-up analysis for over anticoagulation and risk of bleeding in carriers of thrombophilia marker versus non-carriers.


   Acknowledgments Top


Authors are grateful to Indian Council of Medical Research (ICMR), Delhi, India for providing Research Fellowship to one of the authors (TG) (IRIS cell No. 2011-05540).

 
   References Top

1.Nahar R, Saxena R, Deb R, Verma IC. Pharmacogenetic typing for oral anti-coagulant response among factor V Leiden mutation carriers. Indian J Hum Genet 2012;18:326-31.  Back to cited text no. 1
  Medknow Journal  
2.Shalia KK, Doshi SM, Parikh S, Pawar PP, Divekar SS, Varma SP, et al. Prevalence of VKORC1 and CYP2C9 gene polymorphisms in Indian population and its effect on warfarin response. J Assoc Physicians India 2012;60:34-8.  Back to cited text no. 2
    
3.Gaikwad T, Ghosh K, Kulkarni B, Kulkarni V, Ross C, Shetty S. Influence of CYP2C9 and VKORC1 gene polymorphisms on warfarin dosage, over anticoagulation and other adverse outcomes in Indian population. Eur J Pharmacol 2013;710:80-4.  Back to cited text no. 3
    
4.Shetty S, Vora S, Kulkarni B, Mota L, Vijapurkar M, Quadros L, et al. Contribution of natural anticoagulant and fibrinolytic factors in modulating the clinical severity of haemophilia patients. Br J Haematol 2007;138:541-4.  Back to cited text no. 4
    
5.van 't Veer C, Golden NJ, Kalafatis M, Simioni P, Bertina RM, Mann KG. An in vitro analysis of the combination of hemophilia A and factor V (LEIDEN). Blood 1997;90:3067-72.  Back to cited text no. 5
    



 
 
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