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

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 X 10(9)/l (+/- 1 SD; n = 4) fell acutely to 36.8 +/- 12.6 X 10(9)/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 irreversible 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 X 10(9)/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 decreased significantly from 3.89 +/- 0.20 and 2.33 +/- 0.25 mumol/10(11) platelets respectively at baseline to 2.17 +/- 0.37 and 1.68 +/- 0.37 mumol/10(11) platelets respectively after 7 d (P less than 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 greater than 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.