II Medizinische Klinik, Klinikum rechts der Isar der Technischen Universität München, Ismaningerstr 22, 81675 München, Germany.
Crit Care. 2010;14(3):R90. doi: 10.1186/cc9024. Epub 2010 May 20.
Heparin-induced thrombocytopenia (HIT) is a serious, prothrombotic, immune-mediated adverse reaction triggered by heparin therapy. When HIT is diagnosed or suspected, heparins should be discontinued, and an alternative, fast-acting, parenteral, nonheparin anticoagulation such as argatroban should be initiated. Limited and inconsistent data exist about dosing of argatroban in intensive care unit (ICU) patients with critical illnesses.
Retrospective analysis of 12 ICU patients with multiple organ dysfunction syndrome (MODS) treated with argatroban for suspected or diagnosed HIT.
The 12 ICU patients with a mean platelet count of 46,000 +/- 30,310 had a mean APACHE II score of 26.7 +/- 7.8 on ICU admission and a mean SAPS II score of 61.5 +/- 16.3 on the first day of argatroban administration. A mean argatroban starting dose of 0.32 +/- 0.25 microg/kg/min (min, 0.04; max, 0.83) was used to achieve activated partial thromboplastin times (aPTTs) >60 sec or aPTTs of 1.5 to 3 times the baseline aPTT. Adjustment to aPTT required dose reduction in six (50%) patients. Patients were treated for a mean of 5.5 +/- 3.3 days. The final mean dose in these critically ill patients was 0.24 +/- 0.16 microg/kg/min, which is about one eighth of the usually recommended dose and even markedly lower than the previously suggested dose for critically ill ICU patients. In all patients, desired levels of anticoagulation were achieved. The mean argatroban dose was significantly lower in patients with hepatic insufficiency compared with patients without hepatic impairment (0.10 +/- 0.06 microg/kg/min versus 0.31 +/- 0.14 microg/kg/min; P = 0.026). The mean argatroban dose was significantly correlated with serum bilirubin (r = -0.739; P = 0.006).
ICU Patients with MODS and HIT can be effectively treated with argatroban. A decrease in the initial dosage is mandatory in this patient population. Further studies are needed to investigate argatroban elimination and dosage adjustments for critically ill patients.
肝素诱导的血小板减少症（HIT）是一种严重的、促血栓形成的、免疫介导的不良反应，由肝素治疗引发。当诊断或怀疑 HIT 时，应停止使用肝素，并启动替代的、起效迅速的、非肝素的、静脉用抗凝剂，如阿加曲班。目前，关于重症监护病房（ICU）中患有严重疾病的患者使用阿加曲班的剂量数据有限且不一致。
回顾性分析 12 例 ICU 中患有多器官功能障碍综合征（MODS）并接受阿加曲班治疗的疑似或确诊 HIT 患者。
这 12 例 ICU 患者的血小板计数平均为 46,000 +/- 30,310，入院时的急性生理与慢性健康状况评分系统 II（APACHE II）平均评分为 26.7 +/- 7.8，第一天开始使用阿加曲班时的简化急性生理学评分系统 II（SAPS II）平均评分为 61.5 +/- 16.3。阿加曲班起始剂量平均为 0.32 +/- 0.25 microg/kg/min（min，0.04；max，0.83），以达到活化部分凝血活酶时间（aPTT）>60 秒或 aPTT 为基线 aPTT 的 1.5 至 3 倍。6 名（50%）患者需要减少剂量以调整 aPTT。患者的治疗平均持续 5.5 +/- 3.3 天。这些重症患者的最终平均剂量为 0.24 +/- 0.16 microg/kg/min，约为通常推荐剂量的八分之一，甚至明显低于之前建议的重症 ICU 患者的剂量。在所有患者中，均达到了所需的抗凝水平。肝功能不全患者的阿加曲班剂量明显低于无肝损伤患者（0.10 +/- 0.06 microg/kg/min 与 0.31 +/- 0.14 microg/kg/min；P = 0.026）。阿加曲班剂量与血清胆红素显著相关（r = -0.739；P = 0.006）。
患有 MODS 和 HIT 的 ICU 患者可以用阿加曲班有效治疗。在该患者人群中，初始剂量必须减少。需要进一步研究来探讨重症患者的阿加曲班清除率和剂量调整。
