In normal blood clotting, two different fibrin-stabilizing factors are involved: one is found in plasma, the other in platelets. Both are present as inactive precursors. In 1963, the international committee on blood clotting factors decided to assign the name Factor XI11 to the fibrin-stabilizing factor present in circulating blood or plasma.' Now that we are aware that two different fibrin-stabilizing factors (FSF) are involved in clot formation, we must distinguish between plasma and platelet Factor XI11 (F XIII). During clot formation these proenzymes are converted to the active principle by the action of thrombin.2.3 The active enzymes have been termed transamidase, transglutaminase or fibrin~ligase. ~~ We have shown elsewhere that plasma and platelet F XI11 are not identical: they differ in molecular weight, in subunits, and in their carbohydrate and amino acid composition. However, immunochemical studies revealed that they are not completely different molecular entities; they share certain antigenic determinants and are closely related immunochemically.6 Plasma F XI11 seems to be synthesized by the liver while platelet F XI11 originates in the megakaryocyte, which is the platelet precursor.' In cases of inherited Factor XI11 deficiency, both fibrin-stabilizing factors always seem to be absent. Therefore, it was concluded that both enzymes are controlled by one common genetic locus.6 Fibrin-stabilizing factors are present not only in blood; enzymes which can cross-link fibrin molecules were found to occur in many animal tissues.*-ll In man, other fibrin stabilizing activities have been detected thus far in the aortal2 and in the skin.lS We found that extracts from human placentas, too, are highly potent in stabilizing fibrin clots. Further studies revealed the presence of two different fibrin-stabilizing factors in this tissue. The main component has been isolated and obtained in a pure crystalline form." The present paper deals with the isolation and characterization of the fibrinstabilizing factors from human plasma, platelets and placentas. A comparison of the physicochemical as well as immunochemical properties of these factors is made, and the possibilities for therapeutic use of the placental factor are discussed.
Isolation and Physical Characterization of Plasma Factor XI11The procedure we used in purifying plasma F XI11 is summarized in FIGURE 2. Loewy was the first to isolate this factor in pure form. 16 We used his method to precipitate the FSF from plasma with ammonium sulfate at a