brinogen is present in living blood dissolved in the plasma; it is
also present in such fluids as hydrocele or pericardial effusions,
which, though capable of clotting, do not clot spontaneously. Thrombin,
on the other hand, does not exist in living blood, but only makes its
appearance there after blood is shed. It is not yet certain what is the
nature of the final reaction between fibrinogen and thrombin. The
possibilities are, that thrombin may act--(1) by acting upon fibrinogen,
which it in some way converts into fibrin, (2) by uniting with
fibrinogen to form fibrin, or (3) by yielding part of itself to the
fibrinogen which thus becomes converted into fibrin. The experimental
study of the rate of fibrin formation, when different strengths of
thrombin solutions are allowed to act upon a fibrinogen solution, leads
us to the probable conclusion that the first of these three
possibilities is the correct one, and that thrombin therefore exerts a
true ferment action upon fibrinogen. It is known that in the reaction,
in addition to the formation of fibrin, yet another protein makes its
appearance. This is known as fibrinoglobulin, and apparently it arises
from the fibrinogen, so that the change would be one of cleavage into
fibrin and fibrinoglobulin. It is very noteworthy that although the
amount of fibrin formed during the clotting appears very bulky, yet the
actual weight is extremely small, not more than 0.4 grms. from 100 cc.
of blood.

Having ascertained that the clotting is due to the action of thrombin
upon fibrinogen, we now see that the next step to be explained is the
origin of thrombin. It has been shown that the final step in its
formation consists in the combination of another substance, termed
prothrombin, with calcium. Any soluble calcium salt is found to be
effective in this respect, and conversely the removal of soluble calcium
(e.g. by sodium oxalate) will prevent the formation of thrombin and
therefore of clotting.

In the next place it can be proved that prothrombin does not exist as
such in circulating blood, so that the problem becomes an inquiry as to
the origin of prothrombin. Experiment has shown that in its turn
prothrombin arises from yet another precursor, which is named
thrombogen, and that thrombogen also is not to be found in circulating
blood but only makes its appearance after the blood is shed. The
conversion of thrombogen into prothrombin has been proved to be due to
the action of a sec