The Effect of Dilution of Plasma on Coagulation: The Significance of the Dilution‐Activation Phenomenon for the Study of Platelet Coagulant Activities

Summary: The coagulation of non‐contacted plasma is enhanced by dilution with citrate‐saline solution, an effect termed the ‘dilution‐activation phenomenon (DAP)’. When platelets rather than phospholipid were added to plasma, the dilution effect was greatly attenuated. A large clotting time difference between platelet and phospholipid additions was therefore evident when undiluted plasma was tested in plastic tubes. This difference disappeared when the plasma was diluted and tested in glass tubes. Thereby the‘DAP’masked a platelet coagulant activity which appeared to be distinct from platelet factor 3 activity. In order to make meaningful use of a test system for platelets which eliminated the ‘DAP’, it was desirable to ascertain what factors accounted for the clot‐promoting effect of dilution. The experimental evidence suggests that a physicochemical alteration results in factor‐XII activation when plasma is diluted. Physicochemical factors shown to be important in enhancing the‘DAP’and presumably contact activation are alkaline pH, low ionic strength and negative electrochemical charge, whereas positive charge, high ionic strength and acid pH inhibit clotting in the system employed.