影响重组人可溶性血栓调节蛋白对弥散性血管内凝血疗效的因素：一项回顾性研究

Factors influencing the effectiveness of recombinant human soluble thrombomodulin on disseminated intravascular coagulation: a retrospective study.

作者信息

Asai Yuki, Yamamoto Takanori, Kito Daisuke, Ichikawa Kazuya, Abe Yasuharu

机构信息

Pharmacy, National Hospital Organization Mie Chuo Medical Center, 2158-5 Hisaimyojincho, Tsu, Mie, 514-1101, Japan.

出版信息

J Pharm Health Care Sci. 2020 Dec 2;6(1):26. doi: 10.1186/s40780-020-00183-7.

DOI:10.1186/s40780-020-00183-7

PMID:33292809

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7709408/

Abstract

BACKGROUND

Although recombinant human soluble thrombomodulin (rTM) has been widely used to treat disseminated intravascular coagulation (DIC) in Japan, there is no consensus regarding rTM efficacy. Therefore, if the factors influencing rTM efficacy is revealed, it may be possible to demonstrate the effectiveness of rTM by limiting the patients who use rTM. This study investigated the factors of rTM treatment which influence DIC status.

METHODS

This retrospective case-control study enrolled hospitalized adult patients treated with rTM from October 2010 to May 2020. Among these patients, 227 who were diagnosed with DIC according to the Japanese Association for Acute Medicine DIC scoring system were assessed. The primary endpoint was the 28-day mortality after rTM treatment. For Cox-proportional hazards model, explanatory factors determined using univariate analysis with p < 0.1 were used. In addition, some factors considered to affect DIC-related mortality such as age ≥ 75 years, rTM dose ≥380 U/kg, antithrombin III treatment, and diseases with a poor prognosis (sepsis, solid tumors, and trauma) were added as covariates.

RESULTS

Univariate analyses suggested that male sex (p = 0.029), treatment in intensive care unit (p = 0.061), and prothrombin time-international normalized ratio (PT-INR) (p < 0.001) were the factors influencing DIC-related 28-day mortality after rTM treatment. According to Cox-proportional hazard analysis, the adjusted odds ratio for DIC-related 28-day mortality in patients with PT-INR ≥ 1.67 was 2.23 (95% confidence interval: 1.451-3.433, p < 0.001), age ≥ 75 years was 1.57 (95% confidence interval: 1.009-2.439, p = 0.046), and male sex was 1.66 (95% confidence interval: 1.065-2.573, p = 0.025), respectively. As life-threatening bleeding events were not observed, prolonged PT-INR might directly or indirectly affect DIC-related mortality caused by rTM treatment.

CONCLUSION

rTM treatment for DIC was less effective in male patients with PT-INR ≥ 1.67 and age ≥ 75 years.

摘要

背景

尽管重组人可溶性血栓调节蛋白（rTM）在日本已被广泛用于治疗弥散性血管内凝血（DIC），但其疗效尚无定论。因此，如果能揭示影响rTM疗效的因素，或许可以通过限定使用rTM的患者来证明其有效性。本研究调查了影响DIC状态的rTM治疗因素。

方法

这项回顾性病例对照研究纳入了2010年10月至2020年5月期间接受rTM治疗的住院成年患者。在这些患者中，对227例根据日本急性医学协会DIC评分系统诊断为DIC的患者进行了评估。主要终点是rTM治疗后28天的死亡率。对于Cox比例风险模型，使用单因素分析中p < 0.1确定的解释因素。此外，还添加了一些被认为影响DIC相关死亡率的因素作为协变量，如年龄≥75岁、rTM剂量≥380 U/kg、抗凝血酶III治疗以及预后不良的疾病（脓毒症、实体瘤和创伤）。

结果

单因素分析表明，男性（p = 0.029）、在重症监护病房接受治疗（p = 0.061）以及凝血酶原时间-国际标准化比值（PT-INR）（p < 0.001）是影响rTM治疗后DIC相关28天死亡率的因素。根据Cox比例风险分析，PT-INR≥1.67的患者DIC相关28天死亡率的调整比值比为2.23（95%置信区间：1.451 - 3.433，p < 0.001），年龄≥75岁的患者为1.57（95%置信区间：1.009 - 2.439，p = 0.046），男性为1.66（95%置信区间：1.065 - 2.573，p = 0.025）。由于未观察到危及生命的出血事件，延长的PT-INR可能直接或间接影响rTM治疗引起的DIC相关死亡率。