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Title: Microparticles and their role in thrombosis in Behçet's Syndrome and their potential as a biomarker for thrombotic risk
Author: Khan, Abdullah Rubiat (Emon)
ISNI:       0000 0004 7232 6659
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2018
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Thrombosis is common in Behçet’s Syndrome (BS), and there is a clear need both for a better understanding of causation and for biomarkers to enable thrombotic risk assessment. I set out to determine whether plasma microparticles (MP), particularly tissue factor expressing (TF+ MP) were increased in BS. Additionally, I investigated whether MP expressing tissue factor pathway inhibitor (TFPI) were also evident. Finally, I investigated whether these MP had a functional consequence role. MP were prepared from 88 BS patients and 72 healthy controls. The BS group contained 21 patients with a history of thrombosis (Th+) and 67 without (Th-). MP were identified by size and annexin V binding using flow cytometry, and were further analysed with antibodies to surface antigens. Assays used to assess the function of MP were an in-house coagulation lysis assay, calibrated automated thrombin generation assay and Factor Xa generation assay. Total MP numbers were increased in BS compared to HC, as were MP expressing TF and TFPI (all p < 0.001). Amongst BS patients, the Th+ group had increased total and TF positive MP (both p < 0.001) compared to the Th- group, but a lower proportion of TFPI positive MPs (p < 0.05). Consequently, the ratio of TFPI to TF MP counts (TFPI/TF) was significantly lower in Th+ versus Th- BS patients (p < 0.001), with no history of clinical thrombosis in BS patients with a TFPI/TF MP ratio > 0.7. Functional assays revealed no correlation with MP count. I conclude that MP expressing TF are increased in BS, more so in patients with thrombosis. An imbalance between microparticulate TF and TFPI may be pathophysiologically important for thrombosis in BS and may allow improved identification and appropriate treatment of thrombotic risk.
Supervisor: Haskard, Dorian ; Laffan, Michael Sponsor: Maori Education Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral