Hemophilia, how will end the story? Hemophilia A (HA) and B (HB) are the most frequent inherited bleeding disorders caused by defects in the F8C and F9 genes that encode coagulation factor VIII and factor IX, respectively. Both HA and HB are X-linked recessive diseases and have an incidence of 1:5000 and 1:30,000 males, respectively. The diagnosis is based on normal prothrombin time, altered activated partial thromboplastin time and reduced activity of factor VIII or factor IX in plasma. Furthermore, laboratory contributes to identify the inhibitor (an immunoglobulin against the factor that some hemophilic patients develop during therapy) and to reveal acquired hemophilia. Carrier females of HA and HB are tipically asymptomatic and can be identified only by molecular analysis; their evaluation is important, as one third of cases of hemophilia is due to novel mutations and in these cases the mother (and consanguineous females) of the proband have no risk to be carrier. Both diseases are due to a myriad of different mutations (mostly private), so that the molecular diagnosis is based on scanning techniques or gene sequencing. Given the number of hemophilic patients that experience severe perinatal complications, high-risk couples usually require prenatal diagnosis. We revise here our experience on 50 prenatal diagnoses of hemophilia. The clinical heterogeneity of hemophilic patients prompted many groups to study prothrombotic gene variants in these subjects to investigate whether such variants modify the clinical expression of disease. Finally, therapy (using recombinant factors) and, in a near future, gene therapy will change the natural history of hemophilic patients.

Hemophilia, how will end the story?

ZARRILLI, Federica;
2013

Abstract

Hemophilia, how will end the story? Hemophilia A (HA) and B (HB) are the most frequent inherited bleeding disorders caused by defects in the F8C and F9 genes that encode coagulation factor VIII and factor IX, respectively. Both HA and HB are X-linked recessive diseases and have an incidence of 1:5000 and 1:30,000 males, respectively. The diagnosis is based on normal prothrombin time, altered activated partial thromboplastin time and reduced activity of factor VIII or factor IX in plasma. Furthermore, laboratory contributes to identify the inhibitor (an immunoglobulin against the factor that some hemophilic patients develop during therapy) and to reveal acquired hemophilia. Carrier females of HA and HB are tipically asymptomatic and can be identified only by molecular analysis; their evaluation is important, as one third of cases of hemophilia is due to novel mutations and in these cases the mother (and consanguineous females) of the proband have no risk to be carrier. Both diseases are due to a myriad of different mutations (mostly private), so that the molecular diagnosis is based on scanning techniques or gene sequencing. Given the number of hemophilic patients that experience severe perinatal complications, high-risk couples usually require prenatal diagnosis. We revise here our experience on 50 prenatal diagnoses of hemophilia. The clinical heterogeneity of hemophilic patients prompted many groups to study prothrombotic gene variants in these subjects to investigate whether such variants modify the clinical expression of disease. Finally, therapy (using recombinant factors) and, in a near future, gene therapy will change the natural history of hemophilic patients.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11695/4963
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