Kornberg A, Francis C W, Pellegrini V D, Gabriel K R, Marder V J
Department of Medicine, University of Rochester School of Medicine and Dentistry, NY 14642.
Circulation. 1993 Aug;88(2):454-60. doi: 10.1161/01.cir.88.2.454.
Oral anticoagulation is most frequently monitored using the prothrombin time, but an alternative approach is measurement of native, fully carboxylated, prothrombin antigen (NPA). We have correlated results of the prothrombin time and NPA with development of venous thrombosis or bleeding complications in a clinical trial of warfarin prophylaxis following total hip arthroplasty to determine the potential value of NPA measurement for monitoring oral anticoagulation.
Patients in one arm of a prospective, randomized trial received warfarin prophylactically beginning 10 to 14 days before total hip arthroplasty in a dose adjusted to prolong the international normalized ratio (INR) to 1.5 on the day of surgery and 2.5 after surgery. NPA was measured by ELISA, and the prothrombin time was measured using rabbit brain thromboplastin. Samples were tested from 97 patients, and data from 81 patients who had adequate venography were analyzed to correlate test results with occurrence of thrombosis. The prothrombin time and INR were less sensitive than NPA to the lowest intensities of anticoagulation, 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 concentration decreased fourfold, from 200 to 50 micrograms/mL. There was little correlation between either the prothrombin time index or the INR and the development 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 there was no relation between thrombosis and the prothrombin time index or INR. There was no significant correlation between surgical blood loss and prothrombin time index, INR, or NPA concentration. However, patients who received the largest number of transfusions on the day of surgery had significantly lower NPA concentrations than patients who required no transfusion.
These results indicate that the NPA concentration more accurately reflects the antithrombotic effect of warfarin than does prothrombin time and may be superior in monitoring prophylactic oral anticoagulation.
口服抗凝治疗最常通过凝血酶原时间进行监测，但另一种方法是测量天然、完全羧化的凝血酶原抗原（NPA）。在一项全髋关节置换术后华法林预防的临床试验中，我们将凝血酶原时间和NPA的结果与静脉血栓形成或出血并发症的发生情况进行了关联，以确定NPA测量在监测口服抗凝治疗方面的潜在价值。
在前瞻性随机试验的一组患者中，从全髋关节置换术前10至14天开始预防性服用华法林，剂量调整为使手术当天国际标准化比值（INR）延长至1.5，术后延长至2.5。通过ELISA法测量NPA，使用兔脑凝血活酶测量凝血酶原时间。对97例患者的样本进行了检测，并对81例有充分静脉造影的患者的数据进行了分析，以将检测结果与血栓形成的发生情况相关联。在抗凝强度最低时，凝血酶原时间和INR比NPA更不敏感，凝血酶原时间指数从1.0增加到1.3，INR从1.0增加到2.0，而NPA浓度从200微克/毫升降至50微克/毫升，降低了四倍。凝血酶原时间指数或INR与血栓形成的发生之间几乎没有相关性，而发生静脉血栓的患者在手术当天以及术后第1、3、5和7天的NPA浓度显著更高。较高的NPA浓度与静脉血栓形成风险增加相关，但血栓形成与凝血酶原时间指数或INR之间没有关系。手术失血量与凝血酶原时间指数、INR或NPA浓度之间没有显著相关性。然而，手术当天接受输血次数最多的患者的NPA浓度明显低于不需要输血的患者。
这些结果表明，NPA浓度比凝血酶原时间更准确地反映了华法林的抗血栓作用，在监测预防性口服抗凝治疗方面可能更具优势。
