Two New Factors in Blood Coagulation-heparin and Pro-antithrombin

A survey of the results of recent work indicates that at least six different substances are concerned in one way or another in the process of blood coagulation; namely, fibrinogen, thrombin, prothrombin, calcium, antithrombin and the so-called zymoplastic or thromboplastic substances furnished bv the body cells in general, including the blood corpuscles. With regard to the last mentioned factor satisfactory evidence has been obtained to show that the active material in tissue extracts is a phosphatid (1) (cephalin). Work that has been going on in t-his laboratory during the past two or three years shows that we must! add two other substances to this list of fibrin factors. So far as we know, neither of these substances has been recognized by other workers. The two new factors are: First, a phosphatid, not previously described, which exists in various tissues but is found in greatest abundance in the liver. This phosphatid is designated as heparid to indicate its origin from liver. It inhibits coagulation, partially or completely according to the concentration. Second, a substance present in blood plasma and blood serum which is converted into antithrombin by a reaction with heparin. Just as in plasma and serum there is a mother substance from which thrombin is formed, so there is an antecedent substance from which antithrombin is formed. By analogy t’his substance is designated as pro-a,ntithrombin. Frothrombin is activated to thrombin by calcium, the pro-antithrombin is activated to antithrombin by heparin. Preparation of heparin. Attlention was first called to this substance during some work done in this laboratory by Jay McLean (2). In the