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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 ad 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, 1.92 _g/ml), ADP (192, 96, 48, 21.3, 10.6 _M),
ristocetin (1.34, 0.67, 0.27 _g/ml), thrombin (0.096, 0.048, 0.019
units/rnl), F-l 1 Mab (7.2, 3.6, 1.8, 0.4 pg/ml) and epinephrine(12, 6,
2.3, 1.06 pM), 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: I. 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 frown CSA- treated patients and the increased
thrombosis and atherogenesis observed m YZYO in renal transplant
recipients may be due to plasma effects on platelet function