THE THROMBOTIC ACTIVITY OF ACTIVATION PRODUCT*

Abstract
The first step in intrinsic clotting in vitro is the generation of activation product (AP) activity from an interaction between Hageman factor (HF) and plasma thromboplastin antecedent (PTA) initiated by contact with a negatively charged surface such as glass or diatomaceous earth powder (e.g., Speedex). Activation product was prepared free of other known in vitro clotting factor activities both from human serum and from human plasma by elution from Speedex powder. Its thrombotic activity was tested in rabbits using a modification of the biological assay for thrombosis-inducing activity in human serum and human serum fractions designed by Wessler, Reimer and Sheps. This first known intermediate in the formation of intrinsic thromboplastin in vitro was found to possess powerful thrombotic activity. When stasis prevents or delays reticulo-endothelial clearance, small amounts of activation product readily induce thrombosis in the experimental animal. Apparently, inhibitors within stagnant blood cannot block the intrinsic clotting reactions once they have started in vivo. The data strongly suggest that activation product is the moiety in human serum responsible for the serum thrombotic accelerator (STA) phenomenon described by Wessler and his associates.