Prothrombin during Warfarin Treatment

S ummary . Prothrombin levels were studied in a group of hospital controls and a group of patients stabilized on long‐term warfarin treatment. The behaviour of prothrombin was also followed in two healthy subjects given a single oral dose of warfarin, and in four patients starting long‐term treatment with warfarin. Three techniques were employed in studying the changes in prothrombin; the measurement of prothrombin clotting activity, the estimation of total immunologically detectable prothrombin, and the detection of the structurally abnormal form of prothrombin in plasma. The mean plasma prothrombin activity for the hospital controls and the patients stabilized on long‐term warfarin was 266 (range 160–376) and 107 (range 48–192) NIH thrombin units per ml respectively. The mean total immunologically detectable prothrombin concentration was 99 (range 63–132) and 87 (range 61–135) % of the normal reference level, respectively. The differences found were statistically significant. No decrease in the immunologically detectable prothrombin levels, and a very slight fall in prothrombin activity were observed in two healthy subjects, given a single warfarin dose. The abnormal form of prothrombin was first detected 8 and 12 hr after the dose and persisted for at least 6 days in the plasma of both subjects. In patients followed from the start of the warfarin treatment, the abnormal form appeared within 12 hr of the first dose, and became the predominant form in plasma, at the latest, after 84 hr of treatment. The clotting activity fell to below 100 NIH units per ml, whereas the immunologically detectable prothrombin levels decreased after a longer time interval. These results confirm that the major changes in therapeutic anticoagulation are the fall in prothrombin clotting activity and the appearance of an abnormal form of prothrombin in plasma. The levels of the immunologically detectable prothrombin in plasma are affected later and to a lesser extent.