The Effect of Lanthanides and Actinides on Blood Coagulation . I . Evidence for and Properties of a New Serum Thromboplastic Factor

The anticoagulant action of certain cations, particularly some of the lanthanides, has been known for forty years (2-6), and one of them, neodymium, has been used as an antithrombotic agent (4, 6-11). Little is known about the related actinides, such as uranium and thorium. Our interest in thorium derived from studies on the untoward effect of the endotoxin-induced generalized Shwartzman phenomenon on thromboplastin generation (12). Since colloidal thorium dioxide (Thorotrast) can induce the Shwartzman phenomenon (13, 14), and since disturbed coagulation and hemorrhagic phenomena have been observed after its administration (12, 14), its precise effect on coagulation was explored. Interference with clotting both in vivo and in zitro was so marked and specific as to warrant extension of the study to the related elements, lanthanum, neodymium, cerium, and uranium. As a consequence, a hitherto unrecognized clotting factor has been disclosed that is especially vulnerable to this group of elements and essential for the earliest phase of coagulation, the elaboration of intrinsic blood thromboplastin. The factor has been separated from other known coagulation components, and some of its properties are reported in this communication. An accompanying paper describes an assay method and variations of the factor in health and disease. The effect of this unique group of elements draws attention to the vast and as yet unexplored area relating atomic structure of cations to biologic activity of certain proteins.