Biochemical and clinical aspects of megathrombocytes.

Abstract

SummaryHuman platelets have been separated into heavy and light populations by differential centrifugation in specific density media. The heavy‐platelet population has an average volume approximately 2–2.4‐fold that of the light‐platelet population. All eleven enzymes of the Embden‐Meyerhof pathway were examined in both platelet populations. Six of the eleven were found to have a twofold greater content/g wet weight in heavy platelets compared to light platelets. Three of these six: hexokinase, phosphofructokinase, and glyceraldehyde‐3‐P‐dehydroge‐nase were found to be rate‐limiting for glycolysis. The reductive capacity of heavy vs. light platelets was also examined. Heavy platelets contained 1.9‐fold greater GSH, 1.7‐fold greater DPNH, and 1.2‐fold greater TPNH than light platelets. Heavy platelets also contained 1.8‐fold less lipid peroxidation products than light platelets and were 2.4‐fold more resistant to lipid peroxidation catalysed by 0.1 mM FeCl3.Kinetic studies in humans with Se75‐selenomethionine revealed that heavy‐large platelets were young platelets, recently released from the bone marrow, and suggested a transition of heavy‐large platelets to lighter‐smaller platelets.Clinical studies in humans revealed the usefulness of the measurement of the percentage of large platelets (or megathrombocytes) in estimating platelet turnover. An excellent correlation was found between the percentage of megathrombocytes on EDTA peripheral smear (and as determined by volume with Coulter Counter) and the number of megakaryocytes in the bone marrow in all platelet disorders examined with low or normal platelet counts, r=0.70 P < 0.001, except in megaloblastic anemia. In megaloblastic anemia, an increase in the percentage of megathrombocytes was usually found, but in the absence of increased megakaryocyte number. Increased megathrombocyte number (% megathrombocytes X platelet count) could be used to predict compensated thrombocytolytic states: normal platelet counts in the presence of increased platelet turnover. This was detectable in 84 patients. Platelet survival studies with DFP32 were obtained in eight of these patients and found to be exponential and significantly shortened in all eight. Megathrombocyte number was also examined in various clinical disorders (with normal platelet counts) in which increased platelet turnover might be suspected. Significant elevations were noted in SLE (68%), rheumatic heart disease with severe valvular damage (63%), disseminated intravascular coagulation (60%), chronic autoimmune thrombocytopenic purpura “in remission” (55%), and diabetes mellitus with retinopathy (47%).