Laboratory investigation of platelet function in patients with mild bleeding disorders

[摘要] Platelets play a crucial role in haemostasis by preventing bleeding at sites of vascular injury. Inherited or acquired platelet defects can impair haemostasis resulting in bleeding symptoms of varying severity ranging from mild to excessive which can be life threatening. Diagnosis of mild platelet-based bleeding disorders is challenging due to the absence of a gold standard technique and their variable bleeding symptoms and bleeding phenotypes observed in healthy individual as well as other haemostatic disorders. The work in this thesis built on the previous studies in the genotyping and platelet phenotyping project allowing further characterization of inherited platelet function defects in individuals with mild bleeding disorders. Platelet aggregation and secretion in samples from 206 patients were investigated during the course of this thesis and were categorised on the basis of the observed defects. Surprisingly, in over a half of these patients, an ex vivo platelet function defect was not found. The genetic investigation of selected cases using whole exome sequencing identified mutations in number of genes previously known to be critical in platelet biology. This thesis also focused on evaluation of three other platelet techniques by comparison with lumi-aggregometry to assess their overall potential in detecting platelet function defects. Further studies are still needed to further assess the potential of these techniques before they can be applied in routine clinical diagnosis.

[发布机构] University:University of Birmingham;Department:Institute of Inflammation and Ageing

[关键词] Q Science;QH Natural history;QH301 Biology