Phenotyping and genotyping of platelet defects in patient populations enriched in bleeding

[摘要] Inherited platelet disorders vary in their associated bleeding risk. Individuals in families with known platelet gene mutations often have variable bleeding, suggesting that bleeding risk is multifactorial. Inherited platelet disorders are difficult to diagnose due to the absence of a gold standard laboratory technique and their variable bleeding phenotype, which often only manifests after haemostatic challenges. The work in this thesis furthers the previous studies in the genotyping and phenotyping of platelets project by significantly increasing the number of participants, allowing further characterisation of inherited platelet disorders in those with a normal platelet count. A bleeding assessment tool score was also recorded in all newly recruited adults. Two specific groups of patients are also studied: Those with unexplained menorrhagia, in whom the hypothesis was that some have an undiagnosed platelet defect. Those with inherited thrombocytopenia, in whom I sought to develop an assay to assess platelet function, as bleeding risk can not be predicted by platelet count alone, suggesting that qualitative defects may contribute. The genetic basis of platelet defects was investigated in many of the patients, leading to identification of mutations in genes known to be critical in platelet biology, and identification of several possible novel variants.

[发布机构] University:University of Birmingham;Department:Institute of Biomedical Research

[关键词] Q Science;QP Physiology