

20 A MANUAL OF VETERINARY PHYSIOLOGY 



A drop of stale serum will not produce clotting with fibrinogen. 

 The reason why stale serum refuses to act is unknown. 



Thrombin may readily be prepared by extracting a dried blood- 

 clot with water. The addition of a few drops of this extract to 

 hydrocele or pericardial fluid at once causes coagulation, for these 

 fluids contain fibrinogen, but no ferment. Thrombin is a colloid, 

 \ and its resistance to putrefaction suggests it is not a protein 

 i substance. According to some observers, thrombin is present in the 

 circulating blood, but if blood be received with special precautions 

 I directly from an artery into a large bulk of alcohol, the clot, when 

 I dried and extracted as above, yields no thrombin. It seems reason- 

 u able to inf erj hat the blood does not coagulate in the vessels during 

 life, as there is no thrombin present. Nevertheless, if solutions 

 of thrombin are injected into the circulation they do not produce 

 intravascular clotting with the certainty that might be expected, 

 and it has been suggested that in such cases the thrombin has 

 been destroyed in the liver, but the evidence of this is not 

 convincing. We shall look at the question again. 



If thrombin does not exist as such in the blood-stream, to what 

 is its origin to be attributed ? Blood received direct from the 

 vessels into a solution of oxalate of soda will remain indefinitely 

 uncoagulated, but the addition of calcium chloride at once 

 causes clotting. This result was originally explained by saying 

 that the lime in the blood was thrown out of solution by the 

 oxalate, and that the addition of calcium caused coagulation. 

 But an oxalate solution of fibrinogen is coagulated by an oxalate 

 serum containing thrombin. Evidently, therefore, in the first 

 of these two experiments thrombin was absent, and in some way 

 or other was produced by the addition of calcium chloride. It 

 is now supposed that the calcium is not concerned in the action 

 of the thrombin on fibrinogen, but that its function is to assist in 

 the production of thrombin from some antecedent substance. 

 To this substance the name pro-thrombin or thrombogen has 

 been given. According to some views, this substance exists in 

 living blood, while others regard it as a product of the breaking 

 down of the platelets and leucocytes of the blood after the latter 

 has been shed. 



If both thrombin and pro-thrombin are formed after the blood 

 is shed, what is it that stimulates the production of pro-throm- 

 bin ? One view which finds many supporters is that the pro- 

 thrombin is liberated from the disintegrating blood-cells by the 

 action of a kinase,* thrombokinase, which, together with calcium 

 salts, converts thrombogen into thrombin. 



Another view is that the circulating plasma contains throm- 

 bogen, but not thrombokinase, the latter being liberated from the 



* Kinases are activating substances. 



