基于体重的阿加曲班剂量算法在肝素诱导的血小板减少症治疗中的应用。

Internal Medicine, Department of Pharmacy, Methodist Hospital (Clarian Health), Indianapolis, IN 46202, USA.

Ann Pharmacother. 2009 Jan;43(1):9-18. doi: 10.1345/aph.1L213. Epub 2009 Jan 6.

BACKGROUND

Manufacturer recommendations for argatroban use in the setting of heparin-induced thrombocytopenia (HIT) state that the dosage should be titrated to a goal activated partial thromboplastin time (aPTT) of 1.5-3 times the baseline aPTT. The lack of a clear dosing strategy with argatroban may result in delayed stabilization of aPTT. There are no published nomograms to guide the dosing of argatroban.

OBJECTIVE

To study the anticoagulant effect and incidence of bleeding and thrombotic events in patients receiving argatroban, with doses determined using a weight-based nomogram.

METHODS

Patients with suspected or documented HIT at an 800-bed teaching community hospital were prospectively treated, in a nonrandomized, nonblinded manner, with argatroban; dosage adjustments were made according to 1 of 2 variations of a dosing nomogram: standard or hepatic/critically ill. The primary outcomes were time to aPTT stabilization and percentage of patients whose aPTTs were within the therapeutic range of 45-90 seconds at 6, 12, 24, 48, 72, and 96 hours. Secondary outcomes were the percentage of patients whose aPTTs were subtherapeutic, supratherapeutic, or above the therapeutic threshold of 45 seconds at each time interval; incidence of thrombotic events; number of dosage adjustments to achieve stabilization; and number of major bleeding events.

RESULTS

Fifty-one patients were prospectively treated using the standard (n = 34) and hepatic/critically ill (n = 17) nomograms. Mean time to aPTT stabilization was 16.25 hours with the standard nomogram and 27.05 hours with the hepatic/critically ill nomogram. The percentages of patients with aPTTs within the therapeutic range at each time interval were 82.4%, 82.4%, 88.2%, 96.4%, 100%, and 100% with the standard nomogram and 58.8%, 82.4%, 76.5%, 93.3%, 100%, and 90.9% with the hepatic/critically ill nomogram. There were no thrombotic events after the initiation of argatroban. Three cases of major bleeding occurred.

CONCLUSIONS

The nomogram is an effective dosing tool for achieving and maintaining therapeutic levels of anticoagulation.

背景

制造商建议在肝素诱导的血小板减少症（HIT）的情况下使用阿加曲班，剂量应滴定至目标活化部分凝血活酶时间（aPTT）为基础 aPTT 的 1.5-3 倍。阿加曲班缺乏明确的剂量策略可能导致 aPTT 稳定延迟。目前尚无指导阿加曲班剂量的发布的列线图。

目的

研究使用基于体重的列线图确定剂量的阿加曲班在接受治疗的患者中的抗凝效果和出血及血栓事件的发生率。

方法

在一家 800 张床位的教学社区医院，前瞻性地治疗疑似或有记录的 HIT 患者，采用非随机、非盲法阿加曲班治疗，剂量调整根据两种剂量列线图之一进行：标准或肝/危重症。主要结局是 aPTT 稳定的时间和 6、12、24、48、72 和 96 小时时 aPTT 在 45-90 秒治疗范围内的患者百分比。次要结局是每个时间间隔内 aPTT 低于治疗范围、高于治疗范围或高于 45 秒治疗阈值的患者百分比；血栓事件的发生率；达到稳定所需的剂量调整次数；和主要出血事件的数量。

结果

51 例患者前瞻性地使用标准（n = 34）和肝/危重症（n = 17）列线图治疗。标准列线图的 aPTT 稳定时间为 16.25 小时，肝/危重症列线图为 27.05 小时。标准列线图的患者在每个时间间隔内 aPTT 在治疗范围内的百分比分别为 82.4%、82.4%、88.2%、96.4%、100%和 100%，肝/危重症列线图分别为 58.8%、82.4%、76.5%、93.3%、100%和 90.9%。阿加曲班开始后没有发生血栓事件。有 3 例主要出血事件发生。