Therapeutic and Adverse Effects of Thrombomodulin Alfa to Treat Sepsis-Induced Disseminated Intravascular Coagulation
Therapeutic and Adverse Effects of Thrombomodulin Alfa to Treat Sepsis-Induced Disseminated Intravascular Coagulation
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血栓调节蛋白阿尔法治疗脓毒症引起的弥散性血管内凝血的疗效和不良反应
DOI：
10.1097/shk.0000000000001477
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发表时间：
2019
期刊：
影响因子：
3.1
通讯作者：
Yamada Yasuhiko
中科院分区：
文献类型：
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作者：
Imaura Masaharu;Tsumori Miki;Nagase Satoshi;Omura Kazuya;Takahashi Hiroyuki;Hatoyama-Tanaka Saori;Katagiri Fumihiko;Takayanagi Risa;Kanno Hiroshi;Yamada Yasuhiko
在治疗弥散性血管内凝血（DIC）（这是基础疾病如感染和恶性肿瘤的并发症）时，血栓调节蛋白（TM）α的有效血浆浓度范围为300至900 ng/mL;然而，治疗脓毒症诱导的DIC时的适当浓度尚不清楚。因此，我们的目的是确定TM α的血浆浓度与其治疗效果和出血性不良事件之间的关系。首先，我们计算了脓毒性DIC患者的TM α血浆谷浓度。接下来，我们根据患者的血浆浓度将其分为两组，根据600 ng/mL的临界值分为低浓度组和高浓度组。低浓度组和高浓度组分别有14例和35例患者。TM α给药后4天，高浓度组的日本急性医学协会DIC诊断标准评分较基线显著降低2.06分，而低浓度组为0.71分。高浓度组的90天生存率（85.4%）显著高于低浓度组（49.0%）（风险比，0.27; 95%置信区间：0.09-0.86）。相比之下，两组之间严重出血的发生率无显著差异。TM alfa治疗脓毒性DIC的推荐血浆浓度确定为高于600 ng/mL，需要380 U/kg（0.06 mg/kg）剂量才能达到该浓度。
In the treatment of disseminated intravascular coagulation (DIC), which is a complication of underlying diseases such as infections and malignant tumors, effective plasma concentrations of thrombomodulin (TM) alfa range from 300 to 900 ng/mL; however, appropriate concentrations when treating sepsis-induced DIC are unknown. Thus, our aim was to determine the relationship between plasma concentrations of TM alfa and its therapeutic effects, and hemorrhagic adverse events. First, we calculated the plasma trough concentrations of TM alfa in septic DIC patients. Next, we divided patients into two groups according to their plasma concentrations into a low-and high-concentration group based on a cut-off value of 600 ng/mL. Fourteen and 35 patients were included in the low-and high-concentration groups, respectively. The Japanese Association for Acute Medicine DIC diagnostic criteria score 4 days after TM alfa administration decreased significantly by 2.06 points from baseline in the high-concentration group compared with 0.71 points in the low-concentration group. The 90-day survival rate was significantly higher in the high-concentration group (85.4%) than in the low-concentration group (49.0%)(hazard ratio, 0.27; 95% confidence interval: 0.09–0.86). In contrast, the incidence of serious hemorrhage was not significantly different between the groups. The recommended plasma concentration of TM alfa in the treatment of septic DIC was determined to be higher than 600 ng/mL, and a dose of 380 U/kg (0.06 mg/kg) was necessary to achieve this concentration.