Study On The Clinic And Molecular Mechanism Of Hereditary Bleeding Disorders

Both hereditary FXIII deficiency and hereditary afibrinogenaemia are very rare and severe autosomal bleeding disorder with an average frequency of one case in 1~2 million in the general population. To date, owing to the rarity of these two kinds of deficiencies, both clinical and basic problems related to them such as the type and severity of bleeding symptoms, the underlying molecular defects and the actual management of bleeding episodes have not been fully characterized and continue to confront hematologists.Hereditary macrothrombocytopenia is a heterogeneous group of rare bleeding disorders characterized by prolonged bleeding time, thrombocytopenia and giant platelets. The pathogenic mechanism of some macrothrombocytopenias is still unresolved. In addition, some novel disorders were constantly discovered in the last few years. Recently, we found a patient with inherited macrothrombocytopenia, the morphology of whose platelets was very special containing many large electron opaque organelles.Part I: Hereditary afibrinogenemia associated with a novel nonsense mutation in the FGA gene.The molecular basis of hereditary afibrinogenemia is still poorly characterized. Up to date, only 33 abnormalities of genes encoding fibrinogen A alpha-chains (FGA), fibrinogen B beta-chains (FGB), and fibrinogen gamma-chains (FGG) have been identified. Here we reported the identification of the genetic defect underlying afibrinogenamia in a Chinese family. The proposita was a 17-year-old Chinese girl, born of a consanguineous marriage, and consanguinity is a recurrent feature in her family, besides her parents, her paternal grandparents also are first cousins The proposita displayed haemorrhagic manifestations, her blood clotting indices were prolonged and her coagulation factors were in normal ranges, whereas functional and immunological tests indicate absence of fibrinogen (<0.2g/l). The other family members were...