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Title: Platelet interactions and contact phase activation on polymeric catheters.
Author: Rhodes, Nicholas Peter.
ISNI:       0000 0001 2426 157X
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 1992
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There are many conflicting views about the blood-response to polymeric materials. In order to be satisfied that a material performs appropriately when used as a device in contact with blood it must be evaluated under relevant conditions. Central venous catheters suffer from problems related to thrombosis and embolism since they are implanted for very long periods of time within the vascular system. The aim of this study was to evaluate the most appropriate method for assessing catheter thrombogenicity, establish data for a number of relevant parameters and correlate these findings with various physico-chemica1 characteristics of the materials. Accordingly, a dynamic model was developed which allowed the assessment of platelet adhesion by measurement of "Cr-labelled platelets and platelet a-granule and lysosomal secretion by flow cytometry, after labelling with anti- GMPl40 and anti-GPS3 antibodies, in whole blood after the perfusion of the blood along the tubing at physiologically relevant shear rates (up to 1000 s") at 37OC. In addition, contact phase activation was assessed by measuring the time taken for an aliquot of plateletfree plasma to clot after contact with catheter material (partial thromboplastin time or P'IT) and the ability of the materials to cause factor XII activation by measuring the quantity of FXIIa-Cl-Inh complexes formed by enzyme-linked immunosorbent assay after the contact of platelet-free plasma with catheter tubing. An attempt was made at finding the identity of the proteins adsorbed onto silicone using a number of electrophoretic techniques. The ability of the materials to cause haemolysis and the cytotoxicity of an extract derived from the materials after SO days incubation in PBS including the identification of these potential leachables by supercritical fluid extraction was also investigated. In addition, these data were discussed in relation to parameters of surface roughness, as viewed by SEM and the ratio of hard and soft segments appearing at the material surface by XPS. It was found that significant differences could be detected in (i) platelet adhesion, where Pellethane was shown to have poor performance; (ii) a-granule release, where all the polyurethanes displayed better performance than any of the other materials and (iii) lysosomal granule release where most materials fared similarly, except for glass which was much worse. Silicone was shown to be best in the PIT assay, Pellethane worst. Surprisingly, no correlation was found with these results and those from FXIIa assay, where Desmopan and Davathane were highly active. New and important data on the initial activation kinetics and the ability of materials to activate factor XII are shown. Silicone produced the greatest haemolysis, PVC the greatest extract toxicity. No correlation was found between the physico-cbemical data and any of the biocompatibility data.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Biophysics