Platelet aggregation by rat liver. Evidence for ADP as major factor.

Slices of liver as well as other tissues induce marked platelet aggregation in vitro. The physical and chemical properties of the active substance in rat liver ultrafiltrates support the contention that the aggregation-inducing agent is identical with ADP. The active material is absorbed on charcoal, dialyzable through cellophane and filterable through a membrane that retains substances of molecular weight greater than 1000. The tissue factor is thermolabile in liver homogenates but thermostable in ultrafiltrates, indicating that degradative enzymes present in tissue did not pass through the filter along with the active substance. Aggregation activity of the ultrafiltrates was retained after prolonged frozen storage and resisted pronase digestion as well as strong acid and alkali. Platelet-aggregating activity in the filtered samples disappeared after incubation with apyrase. ADP could not be detected directly in the active ultrafiltrates by specific-enzyme assay, probably due to insufficient sensitivity of the method, for undetectable levels of ADP were still sufficient to cause marked platelet aggregation. Investigation of conditions under which ADP may pass from parenchymal cells into vessels may contribute to an understanding of the mechanism of thrombosis associated with ischemic and toxic injury.