Rocky Mountain Poison and Drug Center, University of Colorado Denver, USA.
Ann Pharmacother. 2010 Nov;44(11):1836-9. doi: 10.1345/aph.1P318. Epub 2010 Oct 5.
To describe 3 episodes of low-molecular-weight heparin (LMWH) overdose in 2 patients and discuss the clinical presentations, outcomes, and therapeutic options.
The first patient, a 35-year-old female, presented after an intentional overdose of 72,000 units of dalteparin. The peak measured anti-Xa activity was 6.2 U/mL at 7.5 hours postinjection. No interventions were performed and there were no bleeding complications. The patient presented 20 days later following another overdose of 72,000 units. Anti-Xa activity was 4.5 U/mL 2 hours postinjection. No treatment was given and the patient was discharged with plans for follow-up the next day. There was no evidence of bleeding complications on follow-up. The second patient, a 29-year-old male, presented after an intentional overdose of 480 mg of enoxaparin. The anti-Xa activity was 1.9 U/mL measured 2 hours postinjection. The patient was observed without intervention. There were no bleeding complications.
To our knowledge, there is only one previous report of an LMWH overdose in the literature, an iatrogenic overdose in an infant treated with protamine. In our 3 presented episodes of LMWH overdose, no therapeutic interventions were performed and there were no bleeding complications. Review of the literature regarding the efficacy of protamine and recombinant factor VIIa for reversal of LMWH coagulopathy revealed that protamine is only partially effective and recombinant factor VIIa is effective in in vitro studies and case reports.
In cases of LMWH overdose, observation seems to be appropriate in the absence of clinically significant bleeding. Prolonged monitoring may be necessary for patients with renal failure. Use of protamine or recombinant factor VIIa is not supported by this case series in patients without significant bleeding. There is a lack of data regarding how to treat patients with significant bleeding.
描述 2 例患者中发生的 3 例低分子肝素(LMWH)用药过量事件,并讨论临床表现、结局和治疗选择。
第 1 例患者为 35 岁女性,因故意服用达肝素 72000 单位而就诊。注射后 7.5 小时,检测到的最大抗 Xa 活性为 6.2 U/mL。未进行任何干预,也未发生出血并发症。20 天后,患者再次服用达肝素 72000 单位后再次就诊。注射后 2 小时,抗 Xa 活性为 4.5 U/mL。未给予治疗,患者在无出血并发症的情况下出院,计划次日随访。随访时未发现出血并发症的证据。第 2 例患者为 29 岁男性,因故意服用依诺肝素 480mg 而就诊。注射后 2 小时,抗 Xa 活性为 1.9 U/mL。患者接受观察,未进行干预,也未发生出血并发症。
据我们所知,文献中仅有 1 例 LMWH 用药过量的报道,是在接受鱼精蛋白治疗的婴儿中发生的医源性用药过量。在我们报告的 3 例 LMWH 用药过量事件中,未进行任何治疗干预,也未发生出血并发症。我们查阅了关于鱼精蛋白和重组 VIIa 因子逆转 LMWH 抗凝作用的文献,发现鱼精蛋白仅部分有效,重组 VIIa 因子在体外研究和病例报告中有效。
在 LMWH 用药过量的情况下,在没有明显临床出血的情况下,观察似乎是合适的。对于肾衰竭患者,可能需要进行长时间监测。在没有明显出血的情况下,本病例系列不支持使用鱼精蛋白或重组 VIIa 因子治疗。对于有明显出血的患者,如何治疗缺乏数据。