Contributions of human platelets to the proteolytic activation of blood coagulation factors XII and XI.

Previous studies have suggested that human platelets can promote the activation of factor XI by two different mechanisms, one requiring factor XII and ADP-treated platelets and the other requiring collagen-treated platelets in the apparent absence of factor XII. To investigate these hypotheses. isolated platelets were tested for their capacity to promote the activation and cleavage of purified factors XII and Xl in various mixtures of purified factor XII. kallikrein. high molecular weight (HMW) kininogen. and factor XI. The activation of factor XII or factor XI was tested in clotting assays using plasmas deficient in factor XII. Xl. IX. or VII and the limited proteolytic cleavage of ‘25l-labeled factor XII or Xl was assessed using sodium dodecyl sulfate polyacrylamide gel electrophoresis in the presence of reducing agents. That ADPor collagentreated platelets can promote the proteolytic activation of factor XII in mixtures containing kallikrein and HMW kininogen was shown by: (1 ) the proteolytic cleavage of factor XII; (2) the development of factor XII, coagulant activity; and (3) the proteolytic cleavage of ‘25l-factor Xl. Platelets treated with collagen or thrombin were shown by both coagulant assays and by cleavage studies to participate