The rôle of antithrombin and thromboplastin (thromboplastic substance) in the coagulation of blood / by W.H. Howell.

  • William Henry Howell
Date:
[1911?]
Catalogue details

Licence: Public Domain Mark

Credit: The rôle of antithrombin and thromboplastin (thromboplastic substance) in the coagulation of blood / by W.H. Howell. Source: Wellcome Collection.

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    or kinase which can activate prothrombin only in the presence of, or with the assistance of, calcium does not rest upon direct evidence. To obtain direct evidence for this hypothesis, or indeed to obtain conclusive evidence against it, it will be necessary to secure pure prothrombin and ascertain whether or not it is activated by calcium salts alone. But the alternative hypothesis that the tissue extracts (including the material obtainable from disintegrating leucocytes or blood plates) promote or initiate the clotting of blood not by activat- ing the prothrombin but by neutralizing the antithrombin has the direct experimental basis furnished in this paper. Looking at the matter from this standpoint, the process of normal coagulation may be pictured as follows. In the circulating blood we find as constant constituents, fibrinogen, prothrombin, calcium salts, and antithrombin. The last-named substance holds the prothrombin in combination and thus prevents its conversion or activation to thrombin. When the blood is shed, the disintegration of the cor- puscles (platelets) furnishes material (thromboplastin) which com- bines with the antithrombin and liberates the prothrombin; the latter is then activated by the calcium and acts upon the fibrinogen. According to this view the actual process of coagulation involves only three factors, fibrinogen, prothrombin, and calcium. These three factors exist normally in the circulating blood, but are prevented from reacting by the presence of antithrombin. In the bloods of the vertebrates lower than the mammals the blood when not brought into contact with the external tissues, clots very slowly, and when caught in clean vessels'and promptly centrifugalized the resulting plasma, free from corpuscular elements, may be entirely icoagu- lable. In these animals, therefore, effective clotting, such as is neces- sary to protect them from fatal hemorrhage, depends upon the co- operation of the wounded tissues which furnish the thromboplastin required to neutralize the antithrombin, this latter substance being present in these bloods in greater concentration than in the mamma- lian blood. From this point of view the mammalian blood differs from the bloods of the other vertebrates in that it contains within itself an available source of thromboplastin, most probably in the existence of the easily disintegrating platelets which are not found in the blood of the other vertebrates. It will be noted that according to this hypothesis the circulating
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