Standardization of the Quick prothrombin test; with reference to the statistical significance of variations in the prothrombin concentration with use of a stable thromboplastin of high potency.

W ITH increasing use of tests of the prothrombin concentration as an aid in the diagnosis of diseases of the liver and as a guide in vitamin K and dicumarol therapy,’6 it is imperative that the determinations be accurate. There are many ways of measuring the prothrombin concentration and each admits of numerous sources of error. Even when the most careful technic is practiced, appreciable errors in determining the prothrombin concentration may occur unless the thromboplastin used in the test is properly standardized. Furthermore, the results of the test may be misinterpreted unless the amount of variation due to chance alone is appreciated. The present study was undertaken in order to develop an accurate method of standardization of thromboplastin and to investigate the range of normal variation in the results of the Quick prothrombin test. The Quick prothrombin test7 is an indirect measurement of the plasma prothrombin concentration. It is based on the theory of blood coagulation proposing that thromboplastin in the presence of calcium converts prothrombin to thrombin, which in turn converts fibrinogen to fibrin, the strands of which are the end results of clotting. With rare exceptions, the variations in the concentration of calcium and fibrinogen encountered in man do not affect the blood coagulation time. Therefore the speed of the reaction, after addition of an excess of thromboplastin, is used as a measure of the amount of prothrombin present. The standard of reference is the time required for the reaction to take place in the normal subject. Quick7 states that “the prothrombin concentration in the blood of healthy adults is remarkably constant and this normal level can therefore be designated as He gives a table of prothrombin times corresponding to the various prothrombin concentrations. These values are apparently based on tests made on plasma dilutions in a single oormal subject. When the blood of one subject is used as a standard