THE PROTHROMBIN RESPONSE TO THE PARENTERAL ADMINISTRATION OF LARGE DOSES OF VITAMIN K IN SUBJECTS WITH NORMAL LIVER FUNCTION AND IN CASES OF LIVER DISEASE: A STANDARDIZED TEST FOR THE ESTIMATION OF HEPATIC FUNCTION 1

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Abstract
The prothrombin response to the admn. of 76 mg. of synthetic vit. K on 4 successive days, after resting levels had been previously cletd., is described as a liver function test in both normal controls and patients with hepatic disease. A total of 113 cases were studied, correlating this test with other liver function tests performed in all of the patients and biopsy studies in 24 of the patients. Results were classified as positive, negative, and doubtful, using a maximum response of 47 sec. to separate the positive (over 47 sec.) from the negative (under 45 sec.) tests and classifying as doubtful all maximum responses in the range of 45-47 sec. A negative vit. K tolerance test was found in 42 and a doubtful test in one of 43 cases with no clinical evidence of liver disease. 13 of 14 cases with conditions known to be associated with impaired liver function, but without a specific liver disease, showed a positive vit. K tolerance test. 56 cases with clinical evidence of liver disease showed 45 positive, 6 doubtful, and 5 negative vit. K tolerance tests. The sensitivity of the vit. K tolerance test was borne out by correlation with other tests of liver function (bromsulfalein retention, cephalin-cholesterol flocculation, cholesterol and esters, albumin-globulin, icteric index, and Van den Bergh). Furthermore, in 24 cases where an histologic study of the liver was obtained the vit. K tolerance test was also found to be of greater sensitivity than the other liver function tests used as a specific test reflecting disturbance of liver function. It not only demonstrated alteration in liver capacity to maintain normal prothrombin levels but also showed that it could be used as a sensitive and reliable indicator for the demonstration of over-all hepatic dysfunction. The results suggest that this test should be included with other hepatic function tests to form an inventory of the functional state of the liver.