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Title: β-thromboglobulin : laboratory and clinical studies
Author: Ludlam, Christopher A.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1977
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The plasma concentration of platelet specific releasable proteins, as measured in vitro, might reflect the degree of platelet aggregation and release within the circulation. One such protein, β-thromboglobulin, has recently been isolated. The aim of this study was to develop an assay to measure the plasma concentration of β-thromboglobulin in normal subjects and patients. Although quantitative immunoeleotrophorotic, radiolimmuno diffusion and haemagglutination inhibition assays were set up, those were insufficiently sensitive to detect β-thromboglobulin in plasma and a sensitive and specific radioimmunoasoay was therefore developed. Using the radioimmunoassay, further evidence for the platelet specificity of β-thromboglobulin was obtained. To measure the concentration of β-thromboglobulin in platelet poor plasma its release in vitro was inhibited by collecting blood into tubes containing EDTA, prostaglandin E1 and theophylline at 0-4°c, and centrifuged for one hour at 1900g. With this sample collection procedure the mean plasma β-thromboglobulin concentration from 160 healthy subjects was 30.50 ± 12.59n&/ml and the individual results were normally distributed. The plasma levels in males were similar to those in females and they were not related to the whole blood platelet count. Of interest was the observation that the plasma β-thromboglobulin concentration rose with age. When 51 chromium platelet survival studies were undertaken in 10 healthy subjects the platelet mean lifespan was positively correlated with the reciprocal of the plasma β-thromboglobulin concentration. Studies in patients with a variety of disorders revealed several differences when compared with normal individuals. In patients with myeloproliferative disorders a positive correlation was noted between the whole blood platelet count and the plasma β-thromboglobulin concentration; further, a change in the platelet count during treatment was accompanied by a corresponding alteration in the plasma β-thromboglobulin concentration. Some patients with thromboembolic disease had raised plasma concentrations of β-thromboglobulin, but these did not correlate with the chromium platelet mean lifespan estimations. Raised plasma levels were also observed in some patients with rheumatic heart disease and prosthetic cardiac valves, but the significance of these was not clear. The studies reported in this thesis suggest that knowledge of the plasma β-thromboglobulin concentration may, in future, be useful in the diagnosis and management of a variety of disorders in which platelets participate.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available