Abstract：
BACKGROUND: Antithrombin is a small plasma glycoprotein synthesized in the liver that belongs to the serpin family of serine protease inhibitors and inactivates several enzymes in the coagulation pathway. It plays a leading major factor on coagulation pathway, therefore administration of antithrombin is essential to treat serious clinical conditions such as disseminated intravascular coagulation (DIC). Despite the theoretical benefits of antithrombin supplementation, the optimal antithrombin activity for heparin efficacy and the benefits of antithrombin supplementation in various disease entities are not yet fully understood.
METHODS: The strict administration guidelines on antithrombin III in cases of DIC by the National Health Insurance Service and the Ministry of Food and Drug Safety complied as follows: antithrombin levels below 20 mg/dL in adults; antithrombin activity below 70% of normal in adults; total administration period of antithrombin must be carefully limited to within maximum 3 days, and the total administration dose must be below 7,000 international unit (IU), (loading dose, 1,000 IU in 1 hour: maintenance dose, 500 IU every 6 hours for 3 days).
RESULTS: We identified 76 eligible for analysis according to the above-mentioned criteria in our institution (male/female, 59/17). Forty-four were identified to the non-survivor group and 32 patients were recognized as the survivor group. The baseline parameters in the non-survivor and survivor groups were comparable with no significant differences in age (66.5±18.1 vs. 66.0±16.2 years, P=0.90), sex (32/12 vs. 27/5, P=0.35), hospital length of stay (31.1±34.5 vs. 31.2±26.1 days, P=0.99), sequential organ failure assessment (SOFA) (7.3±2.5 vs. 6.6±2.0, P=0.22), simplified acute physiology score II (SAPS II) (46.0±8.8 vs. 43.5±9.2, P=0.23), cause for DIC (P=0.95), and underlying disease (P=0.38). The levels of antithrombin III on the day just before the administration significantly lower in the non-survivor groups than in the survivor groups (50.1%±13.6% vs. 57.6%±12.5%, P=0.01). The hemoglobin level in the 2nd day and 7th day after antithrombin III administration was significantly different between the non-survivor and survivor groups (9.9±1.9 vs. 11.0±2.0 g/dL, P=0.01, and 9.4±1.8 vs. 10.5±1.6 g/dL, P=0.006). The antithrombin III levels on the day of administration [area under the curve (AUC) =0.672] demonstrated significantly better prediction of mortality than the A antithrombin III levels on 1st day (AUC =0.552), the 2nd day (AUC =0.624), and 7th day (AUC =0.593).
CONCLUSIONS: Our study suggests that the antithrombin administration may be effective tools for DIC treatment, and may be more positively considered, especially in the cases of DIC, which is a frequent complication of septic shock, sepsis, and other critical disease entities and which is associated with a high level of mortality. Furthermore, our study also suggests that the total doses and periods of antithrombin administration, which recommended by national guidelines, may be insufficient, therefore prolongation of period and increase of total dose of antithrombin supplement might be necessary.
METHODS: The strict administration guidelines on antithrombin III in cases of DIC by the National Health Insurance Service and the Ministry of Food and Drug Safety complied as follows: antithrombin levels below 20 mg/dL in adults; antithrombin activity below 70% of normal in adults; total administration period of antithrombin must be carefully limited to within maximum 3 days, and the total administration dose must be below 7,000 international unit (IU), (loading dose, 1,000 IU in 1 hour: maintenance dose, 500 IU every 6 hours for 3 days).
RESULTS: We identified 76 eligible for analysis according to the above-mentioned criteria in our institution (male/female, 59/17). Forty-four were identified to the non-survivor group and 32 patients were recognized as the survivor group. The baseline parameters in the non-survivor and survivor groups were comparable with no significant differences in age (66.5±18.1 vs. 66.0±16.2 years, P=0.90), sex (32/12 vs. 27/5, P=0.35), hospital length of stay (31.1±34.5 vs. 31.2±26.1 days, P=0.99), sequential organ failure assessment (SOFA) (7.3±2.5 vs. 6.6±2.0, P=0.22), simplified acute physiology score II (SAPS II) (46.0±8.8 vs. 43.5±9.2, P=0.23), cause for DIC (P=0.95), and underlying disease (P=0.38). The levels of antithrombin III on the day just before the administration significantly lower in the non-survivor groups than in the survivor groups (50.1%±13.6% vs. 57.6%±12.5%, P=0.01). The hemoglobin level in the 2nd day and 7th day after antithrombin III administration was significantly different between the non-survivor and survivor groups (9.9±1.9 vs. 11.0±2.0 g/dL, P=0.01, and 9.4±1.8 vs. 10.5±1.6 g/dL, P=0.006). The antithrombin III levels on the day of administration [area under the curve (AUC) =0.672] demonstrated significantly better prediction of mortality than the A antithrombin III levels on 1st day (AUC =0.552), the 2nd day (AUC =0.624), and 7th day (AUC =0.593).
CONCLUSIONS: Our study suggests that the antithrombin administration may be effective tools for DIC treatment, and may be more positively considered, especially in the cases of DIC, which is a frequent complication of septic shock, sepsis, and other critical disease entities and which is associated with a high level of mortality. Furthermore, our study also suggests that the total doses and periods of antithrombin administration, which recommended by national guidelines, may be insufficient, therefore prolongation of period and increase of total dose of antithrombin supplement might be necessary.
摘要：
背景：抗凝血酶是在肝脏中合成的一种小的血浆糖蛋白，属于丝氨酸蛋白酶抑制剂的serpin家族，并使凝血途径中的几种酶失活。它在凝血途径中起着主要的主要因素，因此,抗凝血酶的给药对于治疗弥散性血管内凝血(DIC)等严重的临床病症至关重要.尽管理论上补充抗凝血酶有好处，肝素疗效的最佳抗凝血酶活性以及在各种疾病实体中补充抗凝血酶的益处尚未完全了解.
方法：国家健康保险局和食品和药品安全部对DIC的抗凝血酶III的严格管理指南如下：成人抗凝血酶水平低于20mg/dL;成人抗凝血酶活性低于正常水平的70％;抗凝血酶的总给药期必须严格限制在最多3天之内，总给药剂量必须低于7,000国际单位（IU），(负荷剂量,1小时内1,000IU：维持剂量，每6小时500IU，持续3天）。
结果：我们根据我们机构的上述标准（男性/女性，59/17)。非幸存者组确定了44例，幸存者组确定了32例。非幸存者和幸存者组的基线参数具有可比性，年龄无显着差异（66.5±18.1vs.66.0±16.2年，P=0.90),性别（32/12vs.27/5，P=0.35），住院时间（31.1±34.5vs.31.2±26.1天，P=0.99),序贯器官衰竭评估（SOFA）（7.3±2.5vs.6.6±2.0，P=0.22），简化急性生理学评分II（SAPSII）（46.0±8.8vs.43.5±9.2,P=0.23),DIC的原因（P=0.95），和基础疾病（P=0.38）。非幸存者组给药前一天的抗凝血酶III水平显着低于幸存者组（50.1％±13.6％vs.57.6%±12.5%,P=0.01）。抗凝血酶III给药后第2天和第7天的血红蛋白水平在非幸存者组和幸存者组之间存在显着差异（9.9±1.9vs.11.0±2.0g/dL,P=0.01，9.4±1.8vs.10.5±1.6g/dL,P=0.006)。给药当天的抗凝血酶III水平[曲线下面积（AUC）=0.672]显示出明显优于第1天的A抗凝血酶III水平（AUC=0.552）的死亡率预测。第2天（AUC=0.624），和第7天(AUC=0.593)。
结论：我们的研究表明，抗凝血酶可能是治疗DIC的有效工具，可能会得到更积极的考虑，尤其是在DIC的情况下，这是感染性休克的常见并发症，脓毒症,和其他危重疾病实体，并与高死亡率相关。此外，我们的研究还表明，抗凝血酶给药的总剂量和时间，根据国家指导方针的建议，可能是不够的，因此，延长周期和增加抗凝血酶补充的总剂量可能是必要的。
方法：国家健康保险局和食品和药品安全部对DIC的抗凝血酶III的严格管理指南如下：成人抗凝血酶水平低于20mg/dL;成人抗凝血酶活性低于正常水平的70％;抗凝血酶的总给药期必须严格限制在最多3天之内，总给药剂量必须低于7,000国际单位（IU），(负荷剂量,1小时内1,000IU：维持剂量，每6小时500IU，持续3天）。
结果：我们根据我们机构的上述标准（男性/女性，59/17)。非幸存者组确定了44例，幸存者组确定了32例。非幸存者和幸存者组的基线参数具有可比性，年龄无显着差异（66.5±18.1vs.66.0±16.2年，P=0.90),性别（32/12vs.27/5，P=0.35），住院时间（31.1±34.5vs.31.2±26.1天，P=0.99),序贯器官衰竭评估（SOFA）（7.3±2.5vs.6.6±2.0，P=0.22），简化急性生理学评分II（SAPSII）（46.0±8.8vs.43.5±9.2,P=0.23),DIC的原因（P=0.95），和基础疾病（P=0.38）。非幸存者组给药前一天的抗凝血酶III水平显着低于幸存者组（50.1％±13.6％vs.57.6%±12.5%,P=0.01）。抗凝血酶III给药后第2天和第7天的血红蛋白水平在非幸存者组和幸存者组之间存在显着差异（9.9±1.9vs.11.0±2.0g/dL,P=0.01，9.4±1.8vs.10.5±1.6g/dL,P=0.006)。给药当天的抗凝血酶III水平[曲线下面积（AUC）=0.672]显示出明显优于第1天的A抗凝血酶III水平（AUC=0.552）的死亡率预测。第2天（AUC=0.624），和第7天(AUC=0.593)。
结论：我们的研究表明，抗凝血酶可能是治疗DIC的有效工具，可能会得到更积极的考虑，尤其是在DIC的情况下，这是感染性休克的常见并发症，脓毒症,和其他危重疾病实体，并与高死亡率相关。此外，我们的研究还表明，抗凝血酶给药的总剂量和时间，根据国家指导方针的建议，可能是不够的，因此，延长周期和增加抗凝血酶补充的总剂量可能是必要的。
