In vitro thromboxane synthesis of depleted blood platelets following renal transplantation.

Renal transplant rejection is associated with platelet activation in vivo which may lead to partially alpha- and delta-granule-depleted platelets that continue to circulate. These "exhausted" platelets are hemostatically defective. To quantitate the extent of platelet granule depletion following kidney transplantation, we determined intraplatelet levels of beta-thromboglobulin (beta TG), platelet factor 4 (PF4), and serotonin (5-hydroxytryptamine, 5-HT) ex vivo in Triton X-100-treated platelet lysates. To explore biochemical alterations of partially depleted platelets, we studied platelet thromboxane A2 (TXA2) synthesis in citrated platelet-rich plasma (PRP) upon stimulation with thrombin or collagen in 45 recipients of renal allografts and 10 healthy volunteers. The patients were divided into subjects with acute and chronic allograft rejection (N = 15), those with compensated renal failure after kidney transplantation but without evidence of allograft rejection (N = 15), and those with functioning renal transplant (N = 15). The mean intraplatelet content of beta TG (38.6 +/- 4.2 micrograms/10(9) platelets), PF4 (11.8 +/- 1.8 micrograms/10(9) platelets), and 5-HT (274 +/- 31 ng/10(9) platelets) in patients with acute or chronic renal allograft rejection was significantly lower than in other recipients of kidney transplants or healthy volunteers (beta TG: 59.9 +/- 4.7 micrograms/10(9) platelets; PF4: 20.4 +/- 2.3 micrograms/10(9) platelets; 5-HT: 461 +/- 48 ng/10(9) platelets; p less than 0.005 in all cases).(ABSTRACT TRUNCATED AT 250 WORDS)