Date of Award

7-1984

Degree Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Medical Sciences

Supervisor

Dr. R.L. Kinlough-Rathbone

Co-Supervisor

Dr. J.F. Mustard

Abstract

Shortened platelet survival observed in individuals with thromboembolic vascular disease could be due to platelet consumption or turnover in thrombi or platelet turnover on the damaged vessel wall. The object of this study was to examine the relationship between:

a) platelet consumption and exchange in thrombi and platelet survival

b) platelet accumulation and turnover on the injured vessel wall and platelet survival.

Indwelling catheters were inserted into rabbit aortae to induce repeated vessel injury and macroscopic chrombus formation. Radiolabelled platelets monitored platelet participation in thrombosis and platelet accumulation on the injured vessel wall. Morphological studies assessed the thrombus characteristics and the cellular events on the vessel wall.

During the first 24 hours following the insertion of indwelling aortic catheters, thrombi formed, attained their maximum size and maintained a constant weight thereafter. ⁵¹Cr-labelled platelet incorporation into thrombi following the growth, decreased by about 50% by 3 days. Loss of radioactivity from the thrombus during the time when thrombus weight remained constant indicated platelet lysis, phagocytosis or loss of whole platelets from the thrombus.

Both morphological studies and studies using platelets doubly labelled with ¹²⁵I and ⁵¹Cr demonstrated that some of the platelets initially incorporated into thrombi lysed. Studies of changes in platelet density as well as studies showing thrombi retained some capacity to accumulate circulating platelets indicated that platelets exchanged in thrombi and some of the platelets that had participated in thrombus formation returned to the circulation as less dense platelets.

The consumption and exchange of platelets in thrombi during the acute phase of growth correlated with maximal shortening of platelet survival time. When platelet survival studies were carried out 1 week after insertion of the catheter (at a time when thrombus growth had ceased and platelet accumulation into thrombi was decreased) platelet survival continued to be shortened. At this time, the extent of platelet accumulation on the injured vessel wall was similar to that observed at the time of insertion of the catheter suggesting platelet interaction with the injured vessel wall influenced platelet survival.

Studies using long and short catheters demonstrated that short catheters induced comparatively less vessel injury than long catheters but thrombus formation was significantly increased. Platelet survival studies carried out at 3 days after insertion of long or short catheters (when thrombus growth had ceased) indicated that the short catheters had no significant effect on platelet survival whereas long catheters continued to shorten platelet survival time.

In conclusion, extensive thrombus formation with evidence of platelet exchange in thrombi is associated with significant shortening of platelet survival time. However, this effect is detectable only during the acute phase of thrombus formation. In contrast, repeated vessel injury in association with continuing platelet turnover on the vessel wall can shorten platelet survival time.

Therefore, shortened platelet survival time is a manifestation of acute thrombus formation, repeated vessel injury or both.

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