Since the publication (9), some 12 years ago, of a standardized procedure for the study of blood coagulation reactions (in vitro), which has been the basis of a large number of investigations in the senior author's laboratories during the intervening years, there have been significant advances toward the purification of many of the clotting factors. In particular, these advances now permit us to qualify the statement of our 1938 paper that (as compared with the rate of the thrombin-fibrinogen reaction)... "the consideration of amount of fibrin f o r m e d . . , is governed by a different set of factors, notable among which are questions related to quantity of thrombin and weight of the clot (Eagle (7)), neither of which can as yet be dignified with a biochemical signific a n c e . . . " Thrombin (30) and prothrombin 432) of great potency and reasonably satisfactory purity (12) are now available from bovine plasma. Thrombins of other species, e.g. rabbit (29), human (5), in our experience, have proved somewhat less reliable (see below) for research studies. The Human Plasma Fractionation program, developed at Harvard under the direction of Dr. E. J. Cohn (4) and colleagues (8), has yielded successful fibrinogen (and fibrin) preparations and these technics have been adapted to bovine plasma, especially in the instance of "fibrinogen" (fraction I) now commercially available from the Armour Laboratories (24). J. D. Ferry and Morrison (13) and Morrison (27) utilized the Harvard human plasma fractions to obtain a considerable body of data concerning the thrombin-fibrinogen reaction and many aspects of fibrin formation and fibrin yields. Our independent studies on materials of bovine and other species have been carried on for a number of years and the data accumulated for the present publication should be reviewed in the light of the Harvard investigations. It will be noted that we have carried certain confirmatory experiments somewhat further into technical details and have added new data on the topics of "fibrinoplastic" factors, the (alleged) "profibrin" question, and problems relating to thrombin stability.
Recently interest has been expressed in the possibility of reducing the damage to the myocardium after an infarction by the use of fibrinolytic therapy. At this time activator appears to be the ideal thrombolytic agent. Data obtained from 3 patients with acute myocardial infarction are presented. All were treated with fibrinolytic therapy. A rise in the level of fibrinolytic activity was manifested by changes in several components of the clotting system and by increased areas of lysis on heated fibrin plates. Other evidence of improvement included a rapid fall in serum transaminase values. THE USE of anticoagulants in thromboembolic disease is a major contribution to medicine. However, certain well-known hazards accompany their use, and the effectiveness of therapy can only be evaluated statistically. Because of these factors, the medical profession is divided as to the value of anticoagulant therapy. Many are ardent advocates and use it almost routinely, some use it in "selective cases," and others flatly condemn its use.Much remains to be done in the prevention and treatment of myocardial infarction, which is evi¬ denced by the fact that the precipitating cause has not been determined and little progress in the treatment of the disorder has occurred during the past two decades.1 Frequently the basis for coronary occlusion is clot formation-occurring usually at the site of some pathological process in a coronary vessel. Effective anticoagulant therapy is thought to forestall the extension of the existing clot and prevent the forma¬ tion of new thrombi. Considerable interest has re¬ cently been centered around the possibility of using purified streptokinase2 or streptokinase-activated human fibrinolysin to accelerate the lysis of cor¬ onary thrombi.3 Fibrinolytic therapy offers such obvious theoretical advantages in the treatment of coronary thrombosis that its use should be given serious consideration.Laboratory control of anticoagulant therapy has been successful by utilizing the clotting time and prothrombin time determinations with the use of heparin and bishydroxycoumarin (Dicumarol)-like anticoagulants respectively.Since the changes induced in the clotting mecha¬ nism with streptokinase and fibrinolytic enzymes are dramatic and unpredictable, laboratory guides with their use are important. Clot lysis is a slow complex process within the intact animal. Briefly stated, a substance present in human blood ( proactivator ) combines with strep¬ tokinase to form an activator of the normally oc¬ curring profibrinolysin. The resulting active fibrinolysin is a proteolytic enzyme which attacks fibrin, fibrinogen, prothrombin, factor V, factor VII, and several other nonrelated proteins.
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