Interpatient phenotypic inconsistency in severe congenital hemophilia: a systematic review of the role of inherited thrombophilia.
It is well known that the clinical phenotype of hemophilia may vary greatly among patients with the same apparent level of coagulation factor and the same genetic mutation. Thus, patients with severe hemophilia may experience a severe phenotype or only a milder bleeding tendency, suggesting some other moderating influence. To elucidate the mechanism of this heterogeneity, some investigators have recently suggested that inherited thrombophilic factors may play a role in the milder clinical presentation of severe hemophilia. In this review, we summarize current knowledge with respect to the modulation of the clinical phenotype of severe hemophilia by prothrombotic genetic risk factors. Although the published literature seems to indicate a protective effect for the coinheritance of factor V Leiden, the limited data available do not permit any firm conclusions. Further trials on a large population of patients are needed to establish the role of genetic thrombophilia in the phenotypic expression of severe hemophilia.
Franchini
Massimo
M
Department of Pathology and Laboratory Medicine, Immunohematology and Transfusion Center, University Hospital of Parma, Italy. massimo.franchini@azosp.vr.it
Montagnana
Martina
M
Targher
Giovanni
G
Veneri
Dino
D
Zaffanello
Marco
M
Salvagno
Gian Luca
GL
Manzato
Franco
F
Lippi
Giuseppe
G
D001779:Blood Coagulation Factors / Q000235:genetics*; D005165:Factor V / Q000235:genetics*; D005838:Genotype; D006467:Hemophilia A / Q000097:blood / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics; D012307:Risk Factors; D019851:Thrombophilia / Q000097:blood / Q000235:genetics*
D001779:Blood Coagulation Factors; C095381:factor V Leiden; D005165:Factor V