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THE MECHANISM OF BLOOD COAGULA-
TION AND SUBSTITUTION THERAPY
Rosemary Biggs
Medical Research Council, Blood Coagulation Research Unit, Churchill Hospital,
Oxford
The modern era of blood clotting research started in the beginning of
this century in the physiology laboratories with experiments on cat, ox and
horse blood and occasional use of human blood or body fluids. From this
work derives the classical theory of blood coagulation and all recent work
is based on this theory. The theory led to the introduction by Quick (1935)
Ca Clj
Tissue Extract (Thromboplastin)
\
Prothrombin (H)-3-»-Thrombin (la)
\
Fibrinogen (I)-2->Fibrin(Ia)
Fig. 1. The classical theory of blood coagulation.
of the one-stage prothrombin time test and the beginning of clinical labo-
ratory research. The one-stage prothrombin time test consists of making
a mixture of the patient's normal plasma with tissue extract and adding
calcium at optimum concentration. The time taken for clotting to occur
in the mixture can, according to the theory, be related only to the concen-
tration of prothrombin provided that fibrinogen is present in excess. Quick's
test was used on plasma samples from many patients and abnormally long
clotting times were recorded. Thus prothrombin deficiency was diagnosed
and measured and two important advances in medicine followed. These
were, the discovery and use of dicoumarin and the identification of Vitamin
K deficiency. This work, which is the basis of modern theory, placed blood
coagulation firmly in the clinical laboratory. It is from this point that I
would like to start, and what I would like to do is to show you a little if
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