Nakano Yoshihisa, Kondo Takahisa, Osanai Hiroyuki, Murase Yosuke, Nakashima Yoshihito, Asano Hiroshi, Ajioka Masayoshi, Sakai Kazuyoshi, Inden Yasuya, Murohara Toyoaki
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Advanced Medicine in Cardiopulmonary Disease, Nagoya University Graduate School of Medicine, Nagoya, Japan.
J Cardiol. 2015 Mar;65(3):185-90. doi: 10.1016/j.jjcc.2014.07.021. Epub 2014 Sep 2.
Rivaroxaban is currently used to prevent stroke in patients with atrial fibrillation. Measuring coagulation function may help clinicians to understand the effects of this drug and the associated risk of bleeding.
Rivaroxaban was given to 136 patients with non-valvular atrial fibrillation. Mean age was 74.5±9.0 years (men: 63.2%) and mean CHADS2 score (±SD) was 1.8±1.2. Prothrombin times (PTs) and plasma soluble fibrin (SF) levels were examined in 84 out of 136 patients at baseline and at least 2 weeks thereafter. In 48 patients we were able to collect blood at exact times, namely just before and 3h after rivaroxaban administration, corresponding to the trough and peak concentrations. Mean peak PT in 48 patients was 17.1±3.6s and median peak SF level was 1.46μg/mL. Multiple regression analysis showed that female sex, high brain natriuretic peptide, and high dose were independent factors prolonging the peak PT. Patients with peak PTs ≥20s experienced significantly more bleeding events. Among 29 of 46 patients newly treated with rivaroxaban without any previous anticoagulant, we examined coagulation function at the exact trough and peak times. In 29 patients, peak PT was significantly more prolonged than the baseline or trough PT (p<0.001 for both), whereas trough PT was comparable to the baseline PT. In contrast, both trough and peak SF levels in these newly treated patients were significantly reduced than at baseline (p=0.003 and p<0.001, respectively).
In Japanese patients with non-valvular atrial fibrillation receiving rivaroxaban, a prolonged peak PT (≥20s) could indicate increased risk of bleeding, and both trough and peak SF levels were reduced relative to baseline. PT and SF are both valuable measures of coagulation status in patients receiving rivaroxaban, regardless of prior anticoagulant history.
利伐沙班目前用于预防心房颤动患者的中风。测量凝血功能可能有助于临床医生了解该药物的效果及相关出血风险。
对136例非瓣膜性心房颤动患者给予利伐沙班治疗。平均年龄为74.5±9.0岁（男性：63.2%），平均CHADS2评分（±标准差）为1.8±1.2。在136例患者中的84例于基线时及之后至少2周检测凝血酶原时间（PTs）和血浆可溶性纤维蛋白（SF）水平。在48例患者中，我们能够在准确时间采集血液，即在利伐沙班给药前及给药后3小时，分别对应谷浓度和峰浓度。48例患者的平均峰PT为17.1±3.6秒，中位峰SF水平为1.46μg/mL。多元回归分析显示，女性、高脑钠肽和高剂量是延长峰PT的独立因素。峰PT≥20秒的患者出血事件明显更多。在46例新接受利伐沙班治疗且既往未使用过任何抗凝剂的患者中，有29例在准确的谷值和峰值时间检测了凝血功能。在29例患者中，峰PT比基线或谷值PT显著延长（两者p<0.001），而谷值PT与基线PT相当。相比之下，这些新治疗患者的谷值和峰值SF水平均比基线时显著降低（分别为p=0.003和p<0.001）。
在接受利伐沙班治疗的日本非瓣膜性心房颤动患者中，峰PT延长（≥20秒）可能表明出血风险增加，且谷值和峰值SF水平相对于基线均降低。PT和SF都是接受利伐沙班治疗患者凝血状态的有价值指标，无论既往抗凝史如何。
