Joseph, Joanne Emily; (1999) A study of platelet activation in the antiphospholipid syndrome. Doctoral thesis (M.D), UCL (University College London).

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Abstract

The association between thromboembolism and the presence of antiphospholipid antibodies (APA) is well established, however the mechanism of action of APA in the pathogenesis of thrombosis remains elusive. It is likely that many haemostatic factors are involved. Platelet activation in antiphospholipid syndrome (APS) has been investigated previously, but many older studies used techniques which were either insensitive or prone to artefactual changes. Whole blood flow cytometry is a sensitive test of platelet activation which allows detection of various aspects of the activation process. The principle aims of this thesis were to use such techniques to investigate both in vivo and in vitro platelet activation in primary APS (PAPS) and systemic lupus erythematosus (SLE) patients (both with and without secondary APS), and this also necessitated the development of some newer methods. Endothelial cell activation and thrombin generation were also assessed. Evidence of significantly increased in vivo platelet activation (as detected by platelet degranulation, changes in the platelet GPIIb/IIIa complex, and formation of platelet-leukocyte complexes) were found in PAPS, as well as in some cases of SLE. Markers of thrombin generation and endothelial cell activation were also significantly increased in both groups of patients. However, in general these markers did not correlate with each other, suggesting that different processes of activation occur, and this may have been partly due to the effects of different types of therapy (i.e aspirin, warfarin and immunosuppressives). In some assays (particularly the detection of platelet-leukocyte complexes), the changes were more significant in SLE than in PAPS, suggesting a role of autoantibodies in general. Finally, in vitro experiments failed to demonstrate a platelet-activating effect of APA on normal platelets.

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