Studies on Blood Coagulation

Abstract

When blood is shed, a soluble plasma protein, fibrinogen, is converted into a gel-like mass of fbrils in the interstices of which the cellular elements of the blood are retained mechanically to form the blood clot. This may subsequently express serum, the phenomenon of syneresis. Table I represents a condensed and greatly simplified summary of some of the theories which have been suggested concerning the mechanism of this transformation. Without considering them individually or in detail, it is to be noted that according to most of these theories, the conversion of fibrinogen to fibrin is associated with the liberation of an active coagulant, termed thrombin in the absence of any precise information as to its chemical nature. Circulating blood is believed to contain various precursors of thrombin, activators, and inhibiting agents in delicate balance; when blood is shed, this balance is somehow upset, initiating a complex series of consecutive reactions, as the very last step in which thrombin is formed; and this thrombin then reacts with plasma fibrinogen to form fibrin, the basis of the clot.There have been two attempts to turn aside from what we may call these classical theories of coagulation as developed by Schmldt, Hammarsten, Morawitz, Bordet, Howell (1915-17, 1925, and others, with their complex interplay of numerous cellular and plasma constituents, and to substitute instead relatively simple concepts. Thus, Hekma has suggested that the transformation of fibrinogen to fibrin is a reversible sol-gel transformation; that fibrinogen is the alkaline hydrosol of fibrin, coagulation presumably resulting from an unexplained increase in the

The Lipid Distribution of Human Platelets in Health and Disease 1

“…There is some debate as to the exact nature of the factors liberated by platelet disintegration. There can be no doubt as to a thermostable thromboplastic agent which has been identified with cephalin (5,6,7,8); it is questionable whether there is, in addition, a coagulant factor, either of prothrombin-like (1,8) or different (5,9) nature.…”

Studies of Hemophilia. Ii. The Assay of the Antihemophilic Clot-Promoting Principle in Normal Human Plasma With Some Observations on the Relative Potency of Certain Plasma Fractions 1

“…of hemophilic blood will accelerate its coagulation appreciably. The clotpromoting principle, which in its crude form is now active in a dilution of about 1 part in 2.2 million, will probably be found to exhibit much higher activity when it is purified further since the CO, precipitated fraction undoubtedly contains some fibrinogen and prothrombin (3,21,22). …”

Prothromboplastin Activities of Some Mammalian Plasmas and Sera

“…The thromboplastin generation test was carried out according to Biggs and Douglas (1953), the modification of Bell and Alton being adopted (1954), except that oxalated plasma treated with barium sulphate (Ba-plasma) was used instead of aluminium hydroxide-treated citrated plasma. Phospholipid was prepared from sheep brain according to Eagle (1935). The partial thromboplastin test was carried out according to Langdell, Wagner, and Brinkhous (1953 The reaction mixtures contained 0·12 ml Ba-plasma, 0·06 ml homologous serum, 0·6 ml phospholipid suspension, 0·6 ml 0·025M CaCl" 1·02 ml 0·15M NaCl; substrate: homologous plasma.…”