Reduced clinical severity in a mutationally well-characterized cohort of severe hemophilia with associated thrombophilia.

The clinical phenotype in hemophilia generally correlates with the type of mutations. We studied 16 patients with severe hemophilia A (factor VIII and factor VIII:Ag <1%) with intron 22 inversions of the factor VIII gene and 6 patients with hemophilia B, 2 each having a common mutation, for the common prothrombotic markers in the anticoagulant and fibrinolytic cascade. Of the patients, 6 of 10 with "clinically mild" and 1 of 12 with "clinically severe" disease had a deficiency or abnormality of any of the factors studied. Thrombophilia thus modulates the clinical severity of hemophilia as is observed in patients who carry similar mutations.

[1]  K. Ghosh,et al.  Contribution of natural anticoagulant and fibrinolytic factors in modulating the clinical severity of haemophilia patients , 2007, British journal of haematology.

[2]  K. Kurnik,et al.  Effects of the factor V G1691A mutation and the factor II G20210A variant on the clinical expression of severe hemophilia A in children – results of a multicenter study , 2007 .

[3]  J. Windyga,et al.  Prevalence of the intron 22 inversion of the factor VIII gene and inhibitor development in Polish patients with severe hemophilia A. , 2005, Archivum immunologiae et therapiae experimentalis.

[4]  M. Baiget,et al.  Modifier genes in haemophilia: their expansion in the human genome , 2002, Haemophilia : the official journal of the World Federation of Hemophilia.

[5]  A. Lombardi,et al.  Mild bleeding diathesis in a boy with combined severe haemophilia B (C10400→T) and heterozygous factor V Leiden , 2001, Haemophilia : the official journal of the World Federation of Hemophilia.

[6]  D. Mohanty,et al.  Development of inhibitors in patients with haemophilia from India , 2001, Haemophilia : the official journal of the World Federation of Hemophilia.

[7]  R. Junker,et al.  Symptomatic Onset of Severe Hemophilia A in Childhood is Dependent on the Presence of Prothrombotic Risk Factors , 2001, Thrombosis and Haemostasis.

[8]  D. Mohanty,et al.  Milder clinical presentation of haemophilia A with severe deficiency of factor VIII as measured by one‐stage assay , 2001, Haemophilia : the official journal of the World Federation of Hemophilia.

[9]  J. Oldenburg,et al.  Small Deletion/Insertion Mutations within Poly-A Runs of the Factor VIII Gene Mitigate the Severe Haemophilia A Phenotype , 1998, Thrombosis and Haemostasis.

[10]  P. Mannucci,et al.  Low Prevalence of the Factor V Leiden Mutation Among “Severe” Hemophiliacs with a “Milder” Bleeding Diathesis , 1995, Thrombosis and Haemostasis.

[11]  Stylianos E. Antonarakis,et al.  Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A , 1993, Nature Genetics.

[12]  T. Kirkwood,et al.  Discrepancy between One‐stage and Two‐stage Assay of Factor VIII:C , 1978, British journal of haematology.

[13]  M. Baiget,et al.  The prothrombin 20210A allele influences clinical manifestations of hemophilia A in patients with intron 22 inversion and without inhibitors. , 2002, Haematologica.

[14]  P. Green,et al.  Recurrent inversion breaking intron 1 of the factor VIII gene is a frequent cause of severe hemophilia A. , 2002, Blood.