Platelet aggregation: Part I Some effects of the adenosine phosphates, thrombin, and cocaine upon platelet adhesiveness.

PLATELETS IN NATIVE BLOOD ADHERE SPONTANEOUSLY TO GLASS INDEPENDENTLY OF TEMPERATURE: if adenosine diphosphate is added to the blood the adhesiveness of the platelets is increased and this effect is largely independent of temperature. The mono- and triphosphates decrease adhesiveness at 20 degrees C. and 37 degrees C. but have no effect at 0 degrees C.; cocaine inhibits adhesion at 37 degrees C. and at 0 degrees C. Aggregation and viscous metamorphosis of platelets in native plasma is induced at 37 degrees C. by adenosine diphosphate or by thrombin; these reactions do not occur at 0 degrees C. Cocaine and all the other anti-adhesive drugs inhibit thrombin or adenosine diphosphate-induced aggregation. The mono- and tri-phosphates appear to compete with adenosine diphosphate and inhibit aggregation; they also inhibit thrombin-induced aggregation. Aggregation induced by adenosine diphosphate or thrombin is not prevented by any of the usual enzyme inhibitors or uncoupling agents at the appropriate strength. At 37 degrees C. aggregation and viscous metamorphosis induced by adenosine diphosphate or thrombin are reversible, and the addition of more adenosine diphosphate or of thrombin again produces aggregation and viscous metamorphosis. Platelets incubated with adenosine diphosphate but not agitated lose their power to aggregate but when more adenosine diphosphate is added with agitation, then aggregation is again produced. These observations are presumably explained by the finding that intact platelets, but not fragmented platelets, can inactivate adenosine diphosphate. From these results it is tentatively concluded that adhesion may involve intrinsic adenosine diphosphate in the platelet which may be activated by thrombin and inhibited by the added mono- or triphosphate. The anti-adhesive drugs act in a different manner. These phenomena have a remarkable similarity to those concerning mitochondrial swelling.