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Study of 18 functional hemostatic polymorphisms in mucocutaneous bleeding disorders

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Abstract

Hereditary disorders of primary hemostasis, characterized by mucocutaneous bleeding (MCB), are highly prevalent in children. Few cases are clearly monogenic, but the overwhelming majority are classified as mild bleeding disorders, with wide clinical and laboratory heterogeneity suggestive of complex polygenic diseases. In this framework, and by homology with venous thrombosis, some functional polymorphisms affecting the hemostatic system should be considered. We evaluated the role of 18 common hemostatic polymorphisms on the occurrence and severity of MCB in a case–control study including 269 patients and 286 matched controls consecutively recruited. FV Leiden was associated with milder bleeding severity, assessed by a standardized bleeding score (p = 0.013). Multivariate analysis revealed that three additional polymorphisms protected against MCB (F13 Leu34, OR = 0.66; 95% CI, 0.47–0.94; p = 0.024; VKORC1 1173T, OR = 0.59; 95% CI, 0.40–0.87; p = 0.009; and non-O blood group alleles, OR = 0.59; 95% CI, 0.41–0.86; p = 0.006). When combined, these polymorphisms showed an additive protection (OR = 0.24; 95% CI, 0.11–0.52), supporting the polygenic nature of MCB. Our data suggest that some common polymorphisms affecting hemostasis-related genes could protect from bleeding.

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Acknowledgements

We are grateful to C. Martínez, J. Rivera, M.L. Lozano, and L. Navarro-Núñez for help discussions.

Funding

This work was partially supported by 04515/GERM/06 from Fundación Séneca, SAF2006-06212 (MCYT & FEDER), RETICS (RECAVA) from ISCIII, Programa PCI Iberoamérica A/9351/07 from Ministerio de Asuntos Exteriores y de Cooperación, Spain, and Grant No. 1060637 from FONDECYT (Fondo de Desarrollo Científico y Tecnológico), Chile.

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Authors and Affiliations

  1. Centro Regional de Hemodonación, University of Murcia, Ronda de Garay s/n, 30003, Murcia, Spain

    Ana I. Antón, Rocio González-Conejero, Vanessa Roldán, Beatriz Sánchez-Vega, Javier Corral & Vicente Vicente

  2. Department of Hematology-Oncology, School of Medicine, P. Universidad Católica de Chile, Santiago, Chile

    Teresa Quiroga & Diego Mezzano

Authors
  1. Ana I. Antón
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  2. Rocio González-Conejero
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  3. Vanessa Roldán
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  4. Teresa Quiroga
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  5. Beatriz Sánchez-Vega
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  6. Javier Corral
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  7. Vicente Vicente
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  8. Diego Mezzano
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Correspondence to Vicente Vicente.

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Antón, A.I., González-Conejero, R., Roldán, V. et al. Study of 18 functional hemostatic polymorphisms in mucocutaneous bleeding disorders. Ann Hematol 89, 1147–1154 (2010). https://doi.org/10.1007/s00277-010-1000-7

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  • DOI: https://doi.org/10.1007/s00277-010-1000-7

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