Tomoda Masanori, Yasaka Masahiro, Nakanishi Yasuyuki, Takaguchi Goh, Nakamura Asako, Gotoh Seiji, Kuwashiro Takahiro, Okada Yasushi
Department of Cerebrovascular Medicine and Neurology, Clinical Research Institute, National Hospital Organaization, Kyushu Medical Center.
Brain Nerve. 2017 May;69(5):571-576. doi: 10.11477/mf.1416200784.
[Background and purpose] Prothrombin fragment 1+2 (PF1+2) is a sensitive marker for blood coagulation system. In order to evaluate anticoagulant activity in patients treated with warfarin or non-vitamin K antagonist oral anticoagulant (NOAC), we measured plasma levels of PF1+2 and evaluated anticoagulant activity by each anticoagulant agent. [Methods] Subjects were 28 patients, 17 men and 11 women, 77±6 year old, with oral anticoagulant therapy for secondary prevention of stroke. We measured plasma levels of PF1+2 in 70 times in 7 patients treated with warfarin, and 154 times in 27 patients treated with NOAC. PT-INR was simultaneously measured in patients treated with warfarin. [Results] In warfarin treatment groups, PT-INR values were median 1.96 (IQR 1.8-2.1) and PF1+2 levels were median 111 pmol/l (IQR 95-141). All PF1+2 levels were below the upper limit of normal range, but 12 values (17%) of them in 5 patients were below the lower limit of normal range. 8 of the 12 values were at PT-INR below 2.5, and 1 of whom developed intracerebral hemorrhage. Plasma levels of PF1+2 in patients treated with dabigatran 150mg BID, dabigatran 110mg BID, rivaroxaban 15mg QD, rivaroxaban 10mg QD, apixaban 5mg BID, apixaban 2.5mg BID, and edxaban 30mg QD were median 116 pmol/l (IQR 99-136), 132 pmol/l (IQR 99-162), 109 pmol/l (IQR 100-125), 133 pmol/l (IQR 100-177), 88 pmol/l (IQR 76-102), 148 pmol/l (IQR 93-167), 221 pmol/l (IQR 208-234). They were all above the lower limit of the normal range, 3 of which were above the upper limit of the normal range. Excessive suppression of thrombin production was more frequently seen in warfarin treatment than in NOAC treatment (p<0.05). [Conclusion] In warfarin treatment, thrombin production was suppressed excessively in 17%, although it was not in NOAC treatment. (Received September 21, 2016; Accepted December 26, 2016; Published May 1, 2017).
[背景与目的]凝血酶原片段1+2（PF1+2）是血液凝固系统的一个敏感标志物。为评估接受华法林或非维生素K拮抗剂口服抗凝药（NOAC）治疗患者的抗凝活性，我们检测了PF1+2的血浆水平，并评估了每种抗凝剂的抗凝活性。[方法]研究对象为28例患者，男性17例，女性11例，年龄77±6岁，接受口服抗凝药进行卒中二级预防治疗。我们对7例接受华法林治疗的患者检测了70次PF1+2的血浆水平，对27例接受NOAC治疗的患者检测了154次。同时对华法林治疗的患者检测PT-INR。[结果]在华法林治疗组中，PT-INR值中位数为1.96（四分位间距1.8 - 2.1），PF1+2水平中位数为111 pmol/l（四分位间距95 - 141）。所有PF1+2水平均低于正常范围上限，但5例患者中有12个值（17%）低于正常范围下限。这12个值中有8个在PT-INR低于2.5时出现，其中1例发生脑出血。接受达比加群150mg每日两次、达比加群110mg每日两次、利伐沙班15mg每日一次、利伐沙班10mg每日一次、阿哌沙班5mg每日两次、阿哌沙班2.5mg每日两次和依度沙班30mg每日一次治疗的患者，PF1+血浆水平中位数分别为116 pmol/l（四分位间距99 - 136）、132 pmol/l（四分位间距99 - 162）、109 pmol/l（四分位间距100 - 125）、133 pmol/l（四分位间距100 - 177）、88 pmol/l（四分位间距76 - 102）、148 pmol/l（四分位间距93 - 167）、221 pmol/l（四分位间距208 - 23）。它们均高于正常范围下限，其中3个高于正常范围上限。与NOAC治疗相比，华法林治疗中更频繁出现凝血酶生成过度抑制（p<0.05）。[结论]在华法林治疗中，17%的患者凝血酶生成被过度抑制，而在NOAC治疗中未出现这种情况。（2016年9月21日收稿；2016年12月26日接受；2017年5月1日发表）
