Antithromboplastin: the Degeneration of Intrinsic Thromboplastin in Normal Serum

It is well known that a powerful thromboplastin is generated during blood coagulation, and a high titre of thromboplastin can be demonstrated in specimens of fresh serum. Its generation may be observed by means of the thromboplastin generation test (Biggs and Douglas, 1953) when a mixture of antihaemophilic globulin, Christmas factor, platelets, factor V, and factor VII is recalcified. If this test is prolonged beyond the usual six-minute incubation period, it will be noticed that the thromboplastin titre rapidly falls; a mixture, which after five minutes' incubation coagulates the substrate plasma in 10 seconds, may take well over 40 seconds to clot the same plasma after another 10 minutes' incubation. Although this degeneration of thromboplastin must have been noticed by all who have performed the test, there appears to have been little research into the mechanism of its removal. There would seem to be two possibilities: either thromboplastin deteriorates by virtue of its own physical instability, or it is destroyed by a specific antithromboplastin which may be present in plasma or serum. Tocantins has postulated the existence of an antithromboplastin, by which he means an inhibitor of thromboplastin formation (1954). Similarly, circulating anticoagulants, described by Lawrence and Johnson (1942), Munro (1946), Fantl and Nance (1946), Biggs and Macfarlane (1953), Hardisty (1954), Hougie and Fearnley (1954), and many other workers, have no action on formed thromboplastin, and are more correctly described as antithromboplastinogens. During the course of work at this laboratory, the ability of serum to destroy brain thromboplastin was observed, and it has been postulated that there is present in serum an antithromboplastin, the function of which is to remove tissue products and extrinsic thromboplastin from the circulating blood (Berry, 1957). Following these