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Factor V HR2 haplotype: a risk factor for venous thromboembolism in individuals with absence of Factor V Leiden

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Abstract

Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), occurs secondary to a number of hereditary and acquired disorders of hemostasis. A recently recognized polymorphism in Factor V (FV) gene H1299R (also named HR2) has been reported to be a possible risk factor for the development of VTE. The aim of this study is to evaluate the role of HR2 polymorphism in VTE in a group of Lebanese patients. Seventy-three VTE patients and 125 healthy subjects were examined for HR2. The average ages for the patients and controls were 45.0 ± 19.1 years and 35.4 ± 18.6 years, respectively. Sixty patients (82.2%) had DVT, eight patients (11%) had PE, and five patients (6.8%) had both. There was significant association between FV Leiden and VTE (p < 0.001). HR2 haplotype had a prevalence of 16.4% in patients. VTE patients with normal FV were 2.7 times more likely to have the HR2 haplotype as compared to controls with normal FV (p = 0.036, 95% CI = 1.04–7.06). We conclude that the FV HR2 haplotype significantly affects the risk of VTE in subjects with normal FV. This finding entails that screening for the HR2 haplotype should be done in VTE patients with normal FV Leiden results.

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References

  1. Kniffin WD Jr, Baron JA, Barrett J, Birkmeyer JD, Anderson FA Jr (1994) The epidemiology of diagnosed pulmonary embolism and deep venous thrombosis in the elderly. Arch Intern Med 154:861–866 doi:10.1001/archinte.154.8.861

    Article  PubMed  Google Scholar 

  2. White RH (2003) The epidemiology of venous thromboembolism. Circulation 107(23):I4–I8 doi:10.1161/01.CIR.0000078468.11849.66

    PubMed  Google Scholar 

  3. Simioni P, Tormene D, Spiezia L, Tognin G, Rossetto V, Radu C et al (2006) Inherited thrombophilia and venous thromboembolism. Semin Thromb Hemost 32:700–708 doi:10.1055/s-2006-951298

    Article  PubMed  CAS  Google Scholar 

  4. Pymar HC, Creinin MD (2001) The risks of oral contraceptive pills. Semin Reprod Med 19:305–312 doi:10.1055/s-2001-18638

    Article  PubMed  CAS  Google Scholar 

  5. Koeleman BP, Reitsma PH, Bertina RM (1997) Familial thrombophilia: a complex genetic disorder. Semin Hematol 34:256–264

    PubMed  CAS  Google Scholar 

  6. Rosing J, Tans G, Govers-Riemslag JW, Zwaal RF, Hemker HC (1980) The role of phospholipids and factor Va in the prothrombinase complex. J Biol Chem 255:274–283

    PubMed  CAS  Google Scholar 

  7. Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H et al (1994) Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 369:64–67 doi:10.1038/369064a0

    Article  PubMed  CAS  Google Scholar 

  8. Bertina RM, Reitsma PH, Rosendaal FR, Vandenbroucke JP (1995) Resistance to activated protein C and factor V Leiden as risk factors for venous thrombosis. Thromb Haemost 74:449–453

    PubMed  CAS  Google Scholar 

  9. Lunghi B, Iacoviello L, Gemmati D, Dilasio MG, Castoldi E, Pinotti M et al (1996) Detection of new polymorphic markers in the factor V gene: association with factor V levels in plasma. Thromb Haemost 75:45–48 doi:10.1159/000134455

    Article  PubMed  CAS  Google Scholar 

  10. Bernardi F, Faioni EM, Castoldi E, Lunghi B, Castaman G, Sacchi E et al (1997) A factor V genetic component differing from factor V R506Q contributes to the activated protein C resistance phenotype. Blood 90:1552–1557

    PubMed  CAS  Google Scholar 

  11. Castoldi E, Rosing J, Girelli D, Hoekema L, Lunghi B, Mingozzi F et al (2000) Mutations in the R2 FV gene affect the ratio between the two FV isoforms in plasma. Thromb Haemost 83:362–365

    PubMed  CAS  Google Scholar 

  12. Alhenc-Gelas M, Nicaud V, Gandrille S, van Dreden P, Amiral J, Aubry ML et al (1999) The factor V gene A4070G mutation and the risk of venous thrombosis. Thromb Haemost 81:193–197

    PubMed  CAS  Google Scholar 

  13. Faioni EM, Franchi F, Bucciarelli P, Margaglione M, De Stefano V, Castaman G et al (1999) Coinheritance of the HR2 haplotype in the factor V gene confers an increased risk of venous thromboembolism to carriers of factor V R506Q (factor V Leiden). Blood 94:3062–3066

    PubMed  CAS  Google Scholar 

  14. Luddington R, Jackson A, Pannerselvam S, Brown K, Baglin T (2000) The factor V R2 allele: risk of venous thromboembolism, factor V levels and resistance to activated protein C. Thromb Haemost 83:204–208

    PubMed  CAS  Google Scholar 

  15. Benson JM, Ellingsen D, El-Jamil M, Jenkins M, Miller CH, Dilley A et al (2001) Factor V Leiden and factor V R2 allele: high-throughput analysis and association with venous thromboembolism. Thromb Haemost 86:1188–1192

    PubMed  CAS  Google Scholar 

  16. Kostka H, Schwarz T, Schellong S, Mix C, Kuhlisch E, Temelkova-Kurktschiev T et al (2003) Coagulation factor V G allele and HR2 haplotype: factor V activity, activated protein C resistance and risk of venous thrombosis. Blood Coagul Fibrinolysis 14:49–56 doi:10.1097/00001721-200301000-00009

    Article  PubMed  CAS  Google Scholar 

  17. Jadaon MM, Dashti AA (2005) HR2 haplotype in Arab population and patients with venous thrombosis in Kuwait. J Thromb Haemost 3:1467–1471 doi:10.1111/j.1538-7836.2005.01326.x

    Article  PubMed  CAS  Google Scholar 

  18. Zaatari GS, Otrock ZK, Sabbagh AS, Mahfouz RA (2006) Prevalence of factor V R2 (H1299R) polymorphism in the Lebanese population. Pathology 38:442–444 doi:10.1080/00313020600922934

    Article  PubMed  CAS  Google Scholar 

  19. De Stefano V, Finazzi G, Mannucci PM (1996) Inherited thrombophilia: pathogenesis, clinical syndromes, and management. Blood 87:3531–3544

    PubMed  Google Scholar 

  20. Margaglione M, Bossone A, Coalizzo D, D’Andrea G, Brancaccio V, Ciampa A et al (2002) FV HR2 haplotype as additional inherited risk factor for deep vein thrombosis in individuals with a high-risk profile. Thromb Haemost 87:32–36

    PubMed  CAS  Google Scholar 

  21. Castaman G, Lunghi B, Missiaglia E, Bernardi F, Rodeghiero F (1997) Phenotypic homozygous activated protein C resistance associated with compound heterozygosity for Arg506Gln (factor V Leiden) and His1299Arg substitutions in factor V. Br J Haematol 99:257–261 doi:10.1046/j.1365-2141.1997.3993213.x

    Article  PubMed  CAS  Google Scholar 

  22. Faioni EM, Castaman G, Asti D, Lussana F, Rodeghiero F (2004) Association of factor V deficiency with factor V HR2. Haematologica 89:195–200

    PubMed  CAS  Google Scholar 

  23. Castaman G, Faioni EM, Tosetto A, Bernardi F (2003) The factor V HR2 haplotype and the risk of venous thrombosis: a meta-analysis. Haematologica 88:1182–1189

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, P. O. Box 11-0236, Riad El Solh 1107 2020, Beirut, Lebanon

    Zaher K. Otrock, Ghazi Zaatari & Rami A. Mahfouz

  2. Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon

    Ali T. Taher, Wael A. Shamseddeen & Ali Bazarbachi

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  1. Zaher K. Otrock
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  2. Ali T. Taher
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  3. Wael A. Shamseddeen
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  4. Ghazi Zaatari
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  5. Ali Bazarbachi
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  6. Rami A. Mahfouz
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Correspondence to Rami A. Mahfouz.

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Otrock, Z.K., Taher, A.T., Shamseddeen, W.A. et al. Factor V HR2 haplotype: a risk factor for venous thromboembolism in individuals with absence of Factor V Leiden. Ann Hematol 87, 1013–1016 (2008). https://doi.org/10.1007/s00277-008-0543-3

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  • DOI: https://doi.org/10.1007/s00277-008-0543-3

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