Selective decrease in platelet dense granule adenine nucleotides during recovery from acute experimental thrombocytopenia and ensuing thrombocytosis in baboons

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Abstract
Serial measurements of platelet volume, platelet content of adenine nucleotides, .beta.-thromboglobulin (.beta.-TG), platelet factor 4 (PF4) and ex vivo platelet aggregation were made in baboons under basal, steady-state conditions of normal platelet production, and during recovery from acute thrombocytopenia induced by the exposure of flowing blood to spherical glass microbeads. The mean basal platelet count of 509 .+-. 107 .times. 109/l (.+-. 1 SD; n = 4) fell acutely to 36.8 .+-. 12.6 .times. 109/l after the insertion of glass bead columns and blood filters, placed distally, for 60 min into surgically implanted arteriovenous-shunts in heparinized baboons. After the irrversible removal of up to 90% of the baseline circulating platelet population, recovery from thrombocytopenia was characterized by a constant rate of increase in circulating platelet counts (115 .+-. 11 .times. 109/l/d) and a rebound thrombocytosis to 1.5 times the basal platelet count after 7 d. Steadystate thrombocytopoiesis was achieved by 3-4 weeks after the onset of thrombocytopenia. Platelet dense granule ADP and ATP decreases significantly from 3.89 .+-. 0.20 and 2.33 .+-. 0.25 .mu.mol/1014 platelets respectively at baseline to 2.17 .+-. 0.37 and 1.68 .+-. 0.37 .mu.mol/1014 platelets respectively after 7 nd (P < 0.001 in both cases) and normalization was achieved only after 4 weeks. By contrast, the mean platelet volume and platelet content of .beta.-TG and PF4 did not change significantly throughout the course of study (P > 0.1 in both cases). Platelet function, assessed by platelet aggregation ex vivo, demonstrated that platelet function was not impaired despite the significant decrease in dense granule ADP. We conclude that a selective, temporal reduction in platelet dense granule adenine nucleotides reflects changes in the thrombocytopoietic control mechanism secondary to induction of acute thrombocytopenia.