BLOOD 



inhibitors, and even possibly inhibitor precursors which are 

 triggered by an ill-understood combination of circumstances 

 into a forward reaction of almost explosive velocity. On the 

 other side, equally effective conditions exist for neutralizing the 

 active products at a rapid rate; so efficient arc the controls on 

 these reactions that despite the local formation of more than 

 enough thrombin to coagulate the total circulating blood volume, 

 the extent of reaction is effectively restricted. 



It is interesting to consider the comparative aspects of blood 

 clotting mechanisms. In lower forms of life hemostasis depends 

 upon the formation of cellular aggregates. Later, rudimentary 

 mechanisms occur which involve both cellular elements and the 

 fluid phase of the blood. In higher forms, the role of plasma 

 components in clotting becomes the dominant one, while the 

 aggregation of blood cells assumes less physiological importance. 

 In man, the platelets have multiple functions ; they are involved 

 at the beginning of the coagulation process and also retain many 

 properties reminiscent of those of amoebocytes in lower forms, 

 including the tendency to formation of relatively pure platelet 

 thrombi and conferral of retractility to fibrin clots. Budtz- 

 Olsen (7) has suggested that the latter property is an evolutionary 

 holdover which is relatively unimportant in view of the efficiency 

 of the fibrin clot. The formation of thrombi, whether or not 

 an evolutionary holdover of only secondary physiological im- 

 portance, may nevertheless result in serious pathological dis- 

 turbances in the circulatory system. 



Many of the best clues to the nature of the components in- 

 volved in blood coagulation have resulted from quirks of nature 

 in which a deficiency occurs of a single component. These de- 

 ficiencies may be either congenital or acquired ; they have a good 

 chance of being detected (in contrast to other deficiency states) 

 because of the gross disturbances in the over-all clotting mech- 

 anisms which result. Discrete congenital diseases due to the 

 lack of almost every participating factor in clotting have now 

 been observed by many investigators. In more than one in- 

 stance the inability to ascribe the abnormality to known patterns 



667 



