Measurements of 111In-platelet survival and imaging provide a means of assessing the extent of thrombus formation on prosthetic surfaces in vivo. A paratial reduction in platelet dense granule neucleotides has now been demonstrated in patients with Dacron aortic prostheses, indicating that platelets either lose dense granule components following non-lethal interactions with the graft luminal surface, or that granule-rich platelets are selectively removed from the circulation. I propose to investigate the mechanisms involved in the modification of circulating platelet properties resulting from platelet interactions with thrombogenic surfaces in vivo, and to define the clinical usefulness of measuring such changes following placement of Dacron aortic grafts in humans. Initial studies will focus on the relation of platelet age of platelet density, size, in vitro function and granule contents. The extent to which these variables are modified in patients with aortic grafts, and the effects of anti-platelet drug therapy will be investigated. Platelet density cohorts will be isolated on discontinuous Percoll density gradients. Total and thrombin-releasable ADP and ATP will be measured by high performance liquid chromatography; PF4, BetaTG and thrombospondin will be measured by radioimmunoassay. Platelet survival times will be assessed using 111Indium-labeled platelets and simultaneous 14C-serotoning and 111In-labeled platelets will be used to evaluate platelet dense granule behavior in vivo. 34SO4-- will be used to identify platelet age cohorts in baboons. Studies in baboons are designed to evaluate: 1) the extent to which platelet density heterogeneity is related to platelet age; 2) functional differences between platelet age cohorts in vivo; and 3) the extent to which platelets recirculate in an altered state following non-lethal interactions with thrombogenic surfaces in vivo. It is anticipated that these studies will have clinical application in predicting and diagnosing prosthesis-related thrombosis and in identifying those patients who require platelet-suppressive drug therapy.
| Savage, B; Hanson, S R; Harker, L A (1988) Selective decrease in platelet dense granule adenine nucleotides during recovery from acute experimental thrombocytopenia and ensuing thrombocytosis in baboons. Br J Haematol 68:75-82 |
| Savage, B; McFadden, P R; Hanson, S R et al. (1986) The relation of platelet density to platelet age: survival of low- and high-density 111indium-labeled platelets in baboons. Blood 68:386-93 |
