Laboratory methods for the genetic diagnosis of bleeding disorders

Accurate carrier detection and pre-natal diagnosis in haemophilia A and B and in von Willebrand's disease (VWD) can be achieved by genetic analysis. The spectrum of mutations responsible for these three disorders is described. Methods for linkage analysis using intragenic diallelic and multiallelic factor VIII and IX gene polymorphisms are mentioned, and situations where their use in carrier detection is inappropriate or fails are discussed. Linkage analysis for examination of von Willebrand factor gene inheritance in families with VWD is also described. Screening for the factor VIII gene inversion in patients with severe haemophilia A and the use of the factor VIII binding assay as a discriminant test in patients with possible mild haemophilia A or VWD are described. Point mutation screening methods AMD, CSGE, DGGE, SSCP and UHG analysis are also detailed. The variety of possible analyses available to genetically diagnose haemophilia A, B and VWD is explored.