494 
HEMATOLOGY 
CALCIUM IONS 
TISSUE EXTRACT 
(THROMBOPLASTIN) 
'COTHROMBOPLASTIN 
'AUTOPROTHROMBIN III! 
PRETHROMBINi 
FROM PROTHROMBIN 
COMPLEX 
•PLATELET COfACTOR OR AUTOPROTHROMBIN I 
(FM^ OR 
■PLATELET FACTOR S HAGEMAN FACTOR 
•CALCIUM IONS OR 
URINE FACTOR 
If 
OTHER WAYS 
»liiyTDPBflTHBflMBIW Cl^ 
pc-GLOBULIN 
LPLATELET FACTOR S 
LCALCIUM IONS 
rmriflooefl 
BLOOD CLOTTING MECHANISMS 
PEPTIDES 
Figure 1. — The clotting of blood consists of three basic chemical reactions: 
1) The formation of autoprothrombin C (P-Xa, thrombokinase, Stuart factor) 
2) The formation of thrombin 
3) The formation of fibrin 
Thrombin alone, as a proteolytic enzyme, produces fibrin. Autoprothrombin C, another 
proteolytic enzyme, forms thrombin from its precursor. This function of autopro- 
thrombin C is accelerated in a rather specific manner by plasma Ac-globulin, platelet 
factor 3, and calcium ions. The formation of autoprothrombin C can occur spontane- 
ously, but is accelerated in various ways. Acceleration occurs with calcium ions, tissue 
thromboplastin and cothromboplastin (F-VII). The latter group of accelerators leads 
to complete consumption of autoprothrombin III-. Incomplete autoprothrombin III 
utilization and less intensive acceleration of autoprothrombin C formation is obtained 
with calcium ions and platelet factor 3 alone or with platelet factor 3, calcium ions, 
plus platelet cof actor (F-VIII). In like manner, Hageman protein (F-XIIa) serves as 
a platelet cof actor. Autoprothrombin II (F-IX) is another platelet cof actor. It functions 
after being derived from the prothrombin complex. There are other ways to form auto- 
prothrombin C as, for example, with a procoagulant from urine. The supplementation of 
platelet factor 3 activity by any one of the platelet cofactors neither requires nor 
excludes a preferred sequence in which the platelet cofactor activity functions. Possibly 
the order is Hageman protein, platelet cofactor, and lastly platelet cofactor II. Hage- 
man protein is not necessary. 
main fluid and thus be available for studies. In 
that way, it was possible to work in a manner 
which was impossible with mammalian blood, 
because the latter has a tendency to clot even if 
cold conditions are maintained. 
When Heinrik Dam discovered vitamin K in 
1929, he was studying the nutritional require- 
ments of chickens.2 He did not have blood coag- 
ulation in his plan, but wanted to see whether 
this species could live on a cholesterol-low diet. 
They developed a bleeding tendency, which 
proved to be a dietary deficiency not previously 
