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A B S T R A C T The ultrastructure and adenine nucleotide metabolism of platelets from patients with acute leukemia were studied to elucidate possible mechanisms for the platelet dysfunction observed in this clinical setting. Nonstimulated (resting) platelets from leukemic patients varied greatly in size; exhibited marked variation in the number of alpha granules present per cell; had poorly delineated circumferential bands of microtubules; and often grossly dilated open channel systems or cytoplasmic vacuolization. The intracellular concentrations of ATP and ADP were significantly below normal, and the specific radioactivity of ATP and ADP of nonstimulated platelets in leukemia was equivalent to or exceeded that seen in stimulated normal platelets. Addition of ADP or collagen to platelets from leukemic patients was followed by retarded and incomplete shape change, delayed and incomplete centripetal migration of subcellular organelles, impaired degranulation, and the formation of loose aggregates composed of relatively few platelets. Stimulation of "leukemic" platelets with collagen led to the release of significantly subnormal amounts of ATP and ADP and no significant change in the specific radioactivity of the intracellular nucleotides. In contrast to the results in normal platelets, the conversion of ATP to inosine monophosphate and hypoxanthine in platelets in leukemia failed to increase significantly with collagen stimulation. The results indicate that abnormalities exist in the storage pool of adePortions of this work were presented to the 46th Annual

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The effect of aspirin and indomethacin on adherence of human platelets to collagen was assessed by affinity chromatography on collagen/Sepharose. Studies were done using platelets from normal subjects and subjects ingesting aspirin. Blood was anticoagulated with EDTA, EGTA or citrate, and platelets were suspended in plasma or buffer after separation by centrifugation or gel filtration. The adherence to collagen of platelets from subjects ingesting 1200 mg aspirin per day decreased significantly (P less than 0.05 or below). A significant reduction in adherence also occurred after exposure to aspirin and indomethacin in vitro. The reduction in adherence was associated with inhibition of malondialdehyde (MDA) production and was unaffected by the presence of CP/CPK. Exposure of platelets to aspirin at 24 degrees C caused no impairment of adherence. The addition of 1.0 mM Ca++, 0.5 or 1.0 mM Mg++, or 1 mM arachidonic acid significantly diminished the inhibition of adherence by aspirin. Imidiazole had an effect on adherence opposite to that of aspirin. Changes in release of 14C-serotonin in general paralleled changes in adherence. The data suggest that aspirin and indomethacin impair but do not fully inhibit platelet adherence to collagen. Factors affecting this inhibitory activity in our system are the presence of plasma and availability of divalent cation. Platelet-collagen adhesion appears partly dependent upon prostaglandin-thromboxane synthesis and may be promoted by a different pathway that is stimulated by divalent cations and unaffected by inhibition of prostaglandin synthesis.