Glucose metabolism of platelets in shrombocytotic stage of myeloproliferative disorders

Abstract

Thromboembolic and hemorrhagic episodes were encountered not infrequently in the period of thrombocytosis of myeloproliferative disorders; chronic myelogenous leukemia (CML), primary thrombocythemia (P. Th.), myelofibrosis with myeloid metaplasia (MMM) and polycythemia vera (P. V.). Establishment of the early detection and the regimen for prevention of these episodes are mandatory and prompted us to study the biochemical background of abnormalities in platelet functions; absence of second aggregation by epinephrine and of collagen induced aggregation, decreased platelet retention.To analyse glucose metabolism of platelets, to which release reaction and aggregation are dependent as the energy source, we observed the activity of Embden-Meyerhof pathway and TCA cycle by measuring 14C-lactate and 14CO2 production from 14C-6-glucose. Basal metabolism of platelets in three cases of CML, three of P. Th. and one case of each MMM and P. V., were as active as control. Epinephrine stimulated control platelets in 14CO2 and lactate production twice as much of basal level, but could not stimulate platelets of CML. Preincubation of these platelets with PGE2, which alone could not induce metabolic response, brought about enhanced metabolic activity in two of three cases but to the level of control. Platelets in MMM and P. V. behaved similar to those of CML. In primary thrombocythemia, platelets responded to epinephrine in two of three cases as well as contol and exhibited enhanced activity by PGE2.Since these platelets in myeloproliferative disorders, aggregated normally by exogenous ADP, relese mechanism seemed to be suppressed or regulated by feed-back mechanism to raise threshold for thrombus formation. In CML, α-receptor on the platelet membrane seemed to be not sensitive enough for epinephrine to induce metabolic response and production of mediator (s) for release reaction. In thrombocythemia, production of mediator (s) for release reaction might be not enough, in spite of fairly good increse of glycolysis by platelets.With the results obtained by this study, we concluded that metabolic abnormalities exist in the platelets of myeloproliferative disorders, being accompanied with release abnormality. The mechanism how those mediators; cyclic nucleotides, prostaglandins and their metabolites are participating to give rise these abnormalities, is under investigation. Metabolic study as well as kinetic study are promising to detect and evaluate initiation of platelet consumption and hypercoagulable state, and to institute fit therapy to prevent hemorrhagic thrombosis.