DEFECTIVE AGGREGATION IN CIRRHOSIS IS INDEPENDENT OF IN-VIVO PLATELETACTIVATION

Background/Aims: Platelet function abnormalities contribute to the hem ostatic defect in patients with cirrhosis. In this study we evaluated the occurrence of in vivo platelet activation as a possible mechanism of defective platelet aggregation in patients with cirrhosis. Methods: Nine patients with severe (Child B-C) cirrhosis and defective platele t aggregation were studied in comparison with age- and sex-matched hea lthy controls, The presence of activated platelets in the bloodstream was evaluated by fluorescence-activated flow cytometry using antibodie s directed against activation-dependent platelet proteins and by measu ring plasma levels of beta-thromboglobulin and platelet factor 4. Urin ary levels of 11-dehydro-TXB(2) and of 2,3-dinor-TXB(2) were assayed b y radioimmunoassay following chromatographic separation, Results: In u nstimulated platelets, the expression of both GMP 140 and GP 53 was no t significantly different in patients with cirrhosis and in controls, After stimulation with ADP and epinephrine, expression of activation-d ependent antigens was lower in platelets from patients (GMP 140: 0.64 +/- 0.09 vs 0.73 +/- 0.04, p = 0.02; GP 53: 0.41 +/- 0.13 vs 0.54 +/- 0.14). Plasma levels of beta-thromboglobulin and platelet factor 4, as indexes of in vivo platelet activation, were also comparable in the t wo groups of subjects, Urinary levels of 11-dehydro-TXB(2) and of 2,3- dinor-TXB(2), the major systemic metabolites of TXA(2), were significa ntly higher in patients with cirrhosis (1807 +/- 518 vs 341 +/- 121 ng /pg creatinine and 693 +/- 512 vs 205 (93 ng/pg creatinine, respective ly, p < 0.001). However, increased excretion of TXB(2) metabolites was also observed in three patients with chronic autoimmune thrombocytope nia. Conclusions: These data indicate that circulating platelets are n ot activated in cirrhosis, and that defective aggregation is most like ly dependent on the alteration of the transmembrane signaling pathways , The increased urinary excretion of systemic TXA(2) metabolites may b e related to increased intrasplenic platelet destruction.