Haemophilia A

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See haemophilia.

Haemophilia A is the commonest X-linked inherited clotting disorder, associated in the case of one of the many potential gene mutations, with the Royal families of Europe through Queen Victoria. While the diagnosis was clinical historically, with spontaneous bleeding into joints or difficult haemostasis after minor injury and an X-linked family history it is now made of diagnostic blood tests. These have advanced to the degree that the diagnosis can now be made in severe cases at birth (less severe usually needs confirmation at 6 months when Vitamin K levels have normalised), although only directed testing is economical by measuring activity of factor VIII in the cord blood. The plasma activity level of factor VIII can be assessed with one-stage and two-stage or chromogenic assays. These assays can be supplemented by a thrombin generation assay or thromboelastography to further define the clinical heterogeneity. In about a third of patients with mild or moderate haemophilia A, a discrepancy exists between the one-stage assay and the two-stage or chromogenic assay. There are multiple possible defects (over 2000 are known) in what is a very large gene complex. Perhaps a sixth of cases of mild haemophilia A are not able to be characterised by simple gene analysis and need a full genome study to characterise[1]. Current treatment relies on replacement therapy with clotting factors, either at the time of bleeding or as part of a prophylactic schedule. The current major complication of such therapy is the development of neutralising antibodies but was blood product associated infection historically. Adeno-associated virus-murine factor VIII vector therapy has been successfully used and a vector is in commercial development as valoctocogene roxaparvovec.