Summary
Platelet ultrastructure, protein composition, and adenine nucleotide metabolism were
studied in patients ingesting ethanol to elucidate the mechanism of ethanol-induced
changes in platelet function and survival. Serial measurements were made in 2 patients
who maintained blood ethanol levels in excess of 300 mg/100 ml for 3 to 4 weeks. No
major changes in structure or metabolism were detected in platelets from the patient
whose platelet counts remained stable during the ingestion period. By contrast, the
development of thrombocytopenia in the other patient was associated with significantly
reduced intracellular ADP, increased ATP/ADP ratio, decreased release of ADP, increased
specific radioactivity of intracellular ATP and ADP, and increased formation of hypoxanthine.
Additionally, platelets from this patient varied markedly in size, contained giant
granules, and possessed a poorly defined micro-tubular system. After stimulation with
ADP or collagen, centripetal granule migration was retarded, and the aggregates formed
were small and loose. Several large proteins were absent from the supernatant fraction
of sonicated platelets from the thrombocytopenic patient. Exposure of normal platelets
to ethanol in vitro resulted in no detectable change in platelet ultrastructure. The
data indicate that the ethanol-related abnormalities of platelet function are due
in part to subnormal amounts of intracellular ADP and a deficit in the storage pool
of ADP. Additionally, the results suggest that impairment in the release mechanism
to the observed defect in the release reaction.
