RESPONSE OF WASHED PLATELETS FROM CYCLOSPORINE-A AND FK506- TREATED RENAL TRANSPLANT RECIPIENTS TO STIMULATORY AGONISTS DOES NOT DIFFER FROM CONTROLS

Abstract

592 Enhanced platelet aggregation has been reported in ADP-stimulated platelet rich plasma (PRP) from CSA-treated renal transplant recipients (RTR's). In this study, washed platelets from 10 FK506-treated, 5 cyclosporine A-treated RTR's and 8 healthy controls were studied. 35 ml of whole anticoagulated blood was obtained from patients and controls and immediately centrifuged, the platelets isolated and washed using buffer and known platelet inhibitors. Platelet function was measured as initial velocity (IVEL), extent of aggregation (EXT), latency to response(LAT) and secretion(SEC) following the exposure to various final concentrations of collagen(19.2, 9.6, 4.8, 1.92μg/ml), ADP(192, 96, 48, 21.3, 10.6 μM), restocetin(1.34, 0.67, 0.27μg/ml), thrombin(0.096, 0.048, 0.019 units/ml), F-11 Mab (7.2, 3.6, 1.8, 0.4 μg/ml) and epinephrine(12, 6, 2.3, 1.06 μM), with simultaneous measurement of granular ATP release in the presence of luciferin luciferase reagent, using a Chronolog-Lumi aggregometer. CSA vs. FK506 groups did not differ when compared by t-test for age, sex, race hemoglobin, hematocrit, platelet count, albumin, cholesterol, iron and prednisone dose. The CSA pts had longer time since transplant compared with the FK506 pts.(39.0+12.1 vs. 2.6+0.6 months, p<0.005). By one-way ANOVA, FK506-treated patients did not differ significantly from cyclosporine-treated patients and controls when compared for latency, extent of aggregation, initial velocity and secretion for all reagents. There was no statistically significant difference in latency, extent, initial velocity and secretion across the various concentrations for each reagent among the 3 groups. We conclude, in our population: 1. Washed platelets from CSA and FK506 treated pts. behave similarly when exposed to stimulatory agonists; 2. Lack of enhanced aggregation in renal transplant pts. compared with controls, observed in this study, may reflect the use of washed platelets, in contrast to PRP used in previous studies; 3. Thus, the enhanced aggregation observed in PRP from CSA-treated patients and the increased thrombosis and atherogenesis observed in vivo in renal transplant recipients may be due to plasma effects on platelet function.