Factor VIII activated by thrombin, and IX activated by the TF/factor VIIa complex, together activate factor X, leading to thrombin generation and conversion of soluble fibrinogen to insoluble fibrin (px). Haemophilia A and B are disorders characterised by inability to generate cell surface-associated factor Xa. Genetic abnormalities include: inversions within intron 22 of factor VIII gene in 50%, point mutations and deletions. Gross gene alterations common in haemophilia A but infrequent in haemophilia B. This may account for low frequency of inhibitors in haemophilia B. Third of haemophilia B patients have dysfunctional molecule.

Carrier detection and antenatal diagnosis now possible in many cases by direct gene mutation detection. Affected family member usually required. Linkage analysis no longer recommended as first line method.

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