COMPARISON OF NATIVE PROTHROMBIN ANTIGEN WITH THE PROTHROMBIN TIME FOR MONITORING ORAL ANTICOAGULANT PROPHYLAXIS

Background. Oral anticoagulation is most frequently monitored using th e prothrombin time, but an alternative approach is measurement of nati ve, fully carboxylated, prothrombin antigen (NPA). We have correlated results of the prothrombin time and NPA with development of venous thr ombosis or bleeding complications in a clinical trial of warfarin prop hylaxis following total hip arthroplasty to determine the potential va lue of NPA measurement for monitoring oral anticoagulation. Methods an d Results. Patients in one arm of a prospective, randomized trial rece ived warfarin prophylactically beginning 10 to 14 days before total hi p arthroplasty in a dose adjusted to prolong the international normali zed ratio (INR) to 1.5 on the day of surgery and 2.5 after surgery. NP A was measured by ELISA, and the prothrombin time was measured using r abbit brain thromboplastin. Samples were tested from 97 patients, and data from 81 patients who had adequate venography were analyzed to cor relate test results with occurrence of thrombosis. The prothrombin tim e and INR were less sensitive than NPA to the lowest intensities of an ticoagulation, with the prothrombin time index increasing from 1.0 to 1.3 and the INR increasing from 1.0 to 2.0, whereas the NPA concentrat ion decreased fourfold, from 200 to 50 mug/mL. There was little correl ation between either the prothrombin time index or the INR and the dev elopment of thrombosis, whereas NPA concentrations were significantly higher on the day of surgery and on postoperative days 1, 3, 5, and 7 in patients who developed venous thrombosis. Higher concentrations of NPA were associated with an increased risk of venous thrombosis, but t here was no relation between thrombosis and the prothrombin time index or INR. There was no significant correlation between surgical blood l oss and prothrombin time index, INR, or NPA concentration. However, pa tients who received the largest number of transfusions on the day of s urgery had significantly lower NPA concentrations than patients who re quired no transfusion. Conclusions. These results indicate that the NP A concentration more accurately reflects the antithrombotic effect of warfarin than does prothrombin time and may be superior in monitoring prophylactic oral anticoagulation.