The mechanism of action of human accelerator globulin and its relation to other clotting factors.

By MERLE LOVELL LEWIS, PH.D. AND ARNOLD G. WARE, P11.1). T HE CONCEPT of blood coagulationi has undergone drastic revision inn the past decade. A number of different names have beenn gin-cnn to the substannces in serum arid plasma w-hich accelerate the comnversiomn of prothrombin to thrombimn. In ann effort to resolve some of the resultant comnfusiomn inn nomenclature, the Josiah Macy Conference group on blood clottinig amid allied disorders appoiinted a sub-committee comprised of five of the beading w-orkers inn the field. Their object ni-as to arrive at some agreement regardimng the identity or mnonidemntity of various factors involved inn the connversionn of prothrombinn to t.hrombimi. The group recognnized two main plasma accelerators, each of which is-as converted to a more potennt accelerator inn serum. One of these factors, plasma Ac-globulinn or proaccelerin (labile factor, prothrombinn accelerator, plasma prothrombinn accelerator, plasmatic cofactor of thromboplastinn), is converted during spontanneous coagulation or unnder the innfluennce of t-hrombimn to the more active serum Acglobulin or acceberini. It has beenn described by various innvestigators as unnstai)le, mnot adsorbed on barium sulfate, riot influcnnccd by the adminnistrationi of dictimarol, amid occurring in the plasma fraction precipitated between one-third amid oine-half saturationn with ammonnium sulfate. The second accelerator, proconnvertim or SPCA precursor (co-factor V, co-thromboplastin, factor VII), is converted during the course of coagulationi to a more active substance, connvertinn or SPCA. SPCA is said to i)e stable, adsorbed on barium sulfate, decreased by the admimnistrationi of dicumarol ; the presence of Ac-globulini is said to be nnecessary for SPCA to exert its accelerator actiomi. The presenit innvestigationn was undertakemn inn ann effort to elucidate the medianism of action of human Ac-globulin (Ac-G). The results imidicate that there may be actually omnly onne accelerator system inn humann plasma, rather than tw-o. Tie evidence stronigly suggests that plasma Ac-globulinn is comnverted by thrombimi to the much more active serum Ac-globulini, most of ishich is them rapidly imnact inate(I i)V ann inhibitor. There is also en-idence to suggest that unider certainn connditionis there may he a change inn the prothrombini molecule, causinig it to become more easily convented to thrombini.