Browsing by Author "Roldan, Vanessa"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Influence of the F12-4 C > T polymorphism on hemostatic tests
    (LIPPINCOTT WILLIAMS & WILKINS, 2010) Corral, Javier; Anton, Ana I.; Quiroga, Teresa; Gonzalez Conejero, Rocio; Pereira, Jaime; Roldan, Vanessa; Vicente, Vicente; Mezzano, Diego
    The common F12 - 4 C>T polymorphism significantly regulates plasma levels of FXII, the first element of the intrinsic pathway of coagulation. Due to the robust effects that this pathway has on blood coagulation in vitro, the objective of our study was to evaluate the influence of this polymorphism on different hemostatic tests. We studied 46 hemostatic parameters in 566 participants: 280 patients with mucocutaneous bleeding and 286 controls. The F12 - 4T allele, associated with reduced levels of FXII (P<0.001), also significantly delayed the activated partial thromboplastin time (aPTT) expressed as aPTTr (ratio sample plasma/normal pooled plasma). Thus, both patients and controls carrying the T allele had higher aPTTr than C/C homozygous individuals (P<0.001). Interestingly, 92% of healthy controls who had prolonged aPTTr carried the F12 - 4T allele. Moreover, individuals with the F12 - 4T allele also had less thrombin generation (assessed by endogenous thrombin potential, thrombin peak and time to achieve the peak of thrombin) using a test with low tissue factor concentration and explicit contact phase activation. Finally, both patients and controls carrying the F12 - 4T allele also displayed significantly lower FIXc and FVIIc levels than C/C individuals (P<0.01). For all associations except for FVIIc, a gene-dosage effect was observed, and homozygous TT individuals had the farthest values. Our study reveals a significant effect of the F12 - 4 C>T polymorphism on hemostatic tests widely used in routine clinical practice. Blood Coagul Fibrinolysis 21: 632-639 (c) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.
  • No Thumbnail Available
    Item
    Study of 18 functional hemostatic polymorphisms in mucocutaneous bleeding disorders
    (2010) Anton, Ana I.; Gonzalez-Conejero, Rocio; Roldan, Vanessa; Quiroga, Teresa; Sanchez-Vega, Beatriz; Corral, Javier; Vicente, Vicente; Mezzano, Diego
    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.