BLOOD 



thrombin, which is the enzyme for the third, the formation of 

 fibrin. The over-all velocity from beginning to end is extremely 

 rapid and resembles an autocatalytic reaction. Closer analysis, 

 however, reveals that an over-all reaction of this character would 

 result if the rate of the first reaction were the limiting rate for all 

 three. This would be the more likely in the present case, since 

 the product of the first reaction is an enzyme for the second. 

 (There is no reason to believe that the rate of thrombin forma- 

 tion is the limiting rate, especially in light of the startling mass of 

 fibrinogen converted to fibrin by minute amounts of thrombin; 

 vide infra.) Despite this rationalization, the pseudo-autocatalytic 

 nature of the clotting process has led to the use of the term auto- 

 catalytic in much of the literature on blood coagulation. On 

 the other hand, preliminary studies on the kinetics of the second 

 reaction in the author's laboratory have failed to reveal any be- 

 havior attributable to autocatalysis ; the reaction appears to be 

 first-order with respect to prothrombin in so far as studied with 

 purified components. 



A second interesting feature emerges. The rather unusual 

 finding of a rapid over-all reaction involving several components 

 including protein enzymes and the platelets, practically demands 

 that, in the blood stream, most, if not all, of the components be 

 present in a preformed, organized complex. It would other- 

 wise be difficult to understand the rapidity of the reaction, since 

 the rate of formation of an enzyme-substrate complex, as for ex- 

 ample, that of prothrombin, thromboplastin, accelerator globu- 

 lin, convertin, and calcium, would in itself be very slow. This 

 can be readily shown in isolated systems. There is, of course, 

 ample precedent for such a coinplex, but usually, as in the mito- 

 chondria, it assumes a three-dimensional form which exists as a 

 separate phase. There is also good presumptive evidence for 

 a preformed coagulation complex. One clue is the affinity of 

 the platelet for calcium. Platelets can be selectively removed 

 from blood by passage over a cation-exchange resin if a very 

 small proportion of the exchange sites have previously been re- 

 acted with calcium; magnesium does not share this property 



669 



