Our Ancient Heritage in Blood Clotting and Some of Its Consequences

If we look at blood clotting from the point of view of evolution, we can discern three clotting systems in man: (1) the platelet system; (2) the cascade system; and (3) the transamidase system.These systems usually come into operation simultaneously (since they are interconnected), but occasionally it is evident that one or the other dominates the picture.The clotting of blood in the Limulus is an example of clotting exclusively by a platelet system.In this creature, the clotting material is contained in circulating plasma cells which break up in the presence of endotoxin and release a protein which clots in the presence of endotoxin.The circulating cell in the Limulus is a prototype of the platelets.Platelets of vertebrates are usually not very sensitive to bacterial toxin but occasionally they regain sensitivity and, under such conditions, the main danger for thrombosis is the disintegrating platelets which release their own clotting material.The cascade system is a complicated one consisting of the interplay of several clotting factors which act consecutively, one turning the other into an active form, eventually leading to thrombin formation that removes charged peptides from fibrinogen, thereby permitting fibrin molecules to form a clot.The operation of the transamidase system is exemplified in the lobster's blood.In this animal, the plasma fibrinogen is converted into a clot, not by the action of thrombin, but by a transamidase which connects the fibrinogen molecules into a network structure with peptide bonds.In man and in other vertebrates, this system usually supplements the cascade system by linking the aggregated fibrin molecules with peptide bonds, thus converting the clot that is insoluble in urea.Under certain conditions this clotting system, even in vertebrates, gains predominance.For example, in atherosclerotic plaques of rabbits, transamidase accumulates and apparently directly connects fibrinogen molecules, rather than fibrin molecules, into a clot.Additionally, in pregnancy, or under the influence of the contraceptive pills, the concentration of this enzyme increases.I believe that these various aspects of the clotting systems should be kept in mind when we study the thrombus formation.For a brief discussion of these three clotting systems, I shall begin with the cascade system which is more familiar to most students of blood coagulation, but the bulk of the discussion will concern the transamidase system.