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Characterisation of platelet phospholipids in unclassified bleeding disorders and deep vein thrombosis

Obaji, Samya Gwen 2020. Characterisation of platelet phospholipids in unclassified bleeding disorders and deep vein thrombosis. PhD Thesis, Cardiff University.
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Patients with a significant bleeding history and normal routine laboratory tests are labelled as having unclassified bleeding disorder (UBD). Approximately one third of patients with acute deep vein thrombosis (DVT) have no risk factor identified and are labelled idiopathic. The experiments conducted herein investigate whether the phospholipid composition of the platelet membrane is contributory to the clinical phenotype. The ability of platelets and microvesicles to support thrombin generation was investigated using a thrombin generation assay tailored to be sensitive to the phospholipid membrane. Peak thrombin generation supported by washed platelets and microvesicles was reduced in UBD patients compared with healthy controls. Peak thrombin and velocity index were increased in patients with DVT. To determine whether changes in thrombin generation could be attributed to native aminophospholipids in the platelet membrane, Phosphatidylserine (PS) and Phosphatidylethanolamine (PE) were measured by mass spectrometry following thrombinactivation of platelets. The thrombin generation assays were sensitive to externalised PE/PS as demonstrated by the minimal amount of thrombin generated by the platelets of a Scott syndrome patient. Externalised PE/PS species were similar in disease cohorts and healthy controls. Previous studies demonstrate that enzymatically oxidised phospholipids produced rapidly on platelet activation support thrombin generation in vitro. Overall, trends of lower quantities of procoagulant 12-HETE-PE and 12-HETE-PC species were measured in UBDs compared with healthy controls whereas 12-HETE-PE species were higher in DVT patients. Lastly, in UBD patients receiving desmopressin for invasive procedures there was increased externalisation of PS and a trend towards increased peak thrombin generation supported by washed platelets. The observed changes in procoagulant oxidised phospholipids suggest the phospholipid composition of the platelet membrane may be implicated in haemostatic disorders. Desmopressin may be effective in UBD because it increases externalised PS and supports thrombin generation. Further studies are required to confirm these findings.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Medicine
Date of First Compliant Deposit: 30 June 2020
Last Modified: 30 Jun 2020 08:07

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