title: The prothrombin 20210A allele influences clinical manifestations of hemophilia A in patients with intron 22 inversion and without inhibitors.
abstract: OBJECTIVE
  The modulation of disease severity in hemophilia A (HA) patients may be related to the co-inheritance of mutations in genes with a known thrombotic effect such as factor V Leiden (FVL) and prothrombin. In the Spanish population, the prothrombin 20210A (PT20210A) allele is the most prevalent genetic risk factor for venous thromboembolism.
  
  
  METHODS
  We investigated the presence of both mutations in a cohort of 265 hemophiliac patients divided into two groups: I) 140 unrelated patients with moderate and mild HA and II) 125 unrelated patients with severe HA (83 carrying an inversion of intron 22).
  
  
  RESULTS
  In group I, 4 patients had the FVL (2.8% vs. 2.98% controls) and 5 had the PT20210A (3.6% vs. 6.46% controls). In group II, two patients with inversion had the FVL (1.6%) and PT20210A was found in 10 patients (8%), five of them with inversion of intron 22 without inhibitors. One of these patients had the FVL and PT20210A mutations concomitantly. In the subgroup of patients with inversion who were carriers of the PT20210A, three parameters i.e. spontaneous bleeding (p=0.008), factor VIII utilization (p=0.016) and number of hemophilic arthropathies (p<0.0005) were significantly lower than in a subgroup of 11 age-matched non-PT20210A severe HA patients with inversion and without inhibitors.
  
  
  CONCLUSIONS
  These results indicate that the inheritance of PT20210A could be a protective factor that mitigates the clinical severity of HA.
authors.affiliation: Servei de Genètica, Hospital de Sant Pau, Padre Claret 167, 08025, Barcelona, Spain. etizzano@hsp.santpau.es
authors.forename: Eduardo F
authors.initials: EF
authors.lastname: Tizzano
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Soria
authors.forename: Immaculada
authors.initials: I
authors.lastname: Coll
authors.forename: Blanca
authors.initials: B
authors.lastname: Guzmán
authors.forename: Mónica
authors.initials: M
authors.lastname: Cornet
authors.forename: Carmen
authors.initials: C
authors.lastname: Altisent
authors.forename: Marta
authors.initials: M
authors.lastname: Martorell
authors.forename: Montserrat
authors.initials: M
authors.lastname: Domenech
authors.forename: Elisabeth
authors.initials: E
authors.lastname: del Río
authors.forename: Jordi
authors.initials: J
authors.lastname: Fontcuberta
authors.forename: Montserrat
authors.initials: M
authors.lastname: Baiget
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D007446:Chromosome Inversion; D005165:Factor V / Q000032:analysis; D005820:Genetic Testing; D006467:Hemophilia A / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology; D006470:Hemorrhage / Q000097:blood / Q000209:etiology / Q000235:genetics; D006801:Humans; D007223:Infant; D007438:Introns / Q000235:genetics; D007518:Isoantibodies / Q000097:blood; D015995:Prevalence; D011516:Prothrombin / Q000032:analysis / Q000235:genetics*
chemical_list: D007518:Isoantibodies; C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin