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COVID-19 和非 COVID-19 危重症患者中,那屈肝素预防血栓形成时抗因子 Xa 水平的变化较大。

Large variation in anti-factor Xa levels with nadroparin as thromboprophylaxis in COVID-19 and non-COVID-19 critically ill patients.

机构信息

Department of Clinical Pharmacy, Rijnstate Hospital, Arnhem, The Netherlands.

Department of Internal Medicine and Intensive Care, Rijnstate Hospital, Arnhem, The Netherlands.

出版信息

BMC Pharmacol Toxicol. 2024 Feb 6;25(1):16. doi: 10.1186/s40360-024-00733-x.

Abstract

PURPOSE

Critically ill COVID-19 and non-COVID-19 patients receive thromboprophylaxis with the LMWH nadroparin. Whether a standard dosage is adequate in attaining the target anti-FXa levels (0.20-0.50 IU/ml) in these groups is unknown.

METHODS

This study was a prospective, observational study in the ICU of a large general teaching hospital in the Netherlands. COVID-19 and non-COVID-19 patients admitted to the ICU who received LMWH in a prophylactic dosage of 2850 IU, 5700 IU or 11400 IU subcutaneously were eligible for the study. Anti-FXa levels were determined 4 h after administration. Relevant laboratory parameters, prespecified co-variates and clinical data were extracted from the electronic health record system. The primary goal was to evaluate anti-FXa levels in critically ill patients on a prophylactic dosage of nadroparin. The second goal was to investigate whether covariates had an influence on anti-FXa levels.

RESULTS

A total of 62 patients were included in the analysis. In the COVID-19 group and non-COVID-19 group, 29 (96%) and 12 patients (38%) reached anti-FXa levels above 0.20 IU/ml, respectively. In the non-COVID-19 group, 63% of the patients had anti-FXA levels below the target range. When adjusted for nadroparin dosage a significant relation was found between body weight and the anti-FXa level (p = 0.013).

CONCLUSION

A standard nadroparin dosage of 2850 IU sc in the critically ill patient is not sufficient to attain target anti-FXa levels in the majority of the studied patient group. We suggest a standard higher dosage in combination with body-weight dependent dosing as it leads to better exposure to nadroparin.

CLINICAL TRIALS REGISTRATION

Retrospectively registered, ClinicalTrials.gov ID NTC 05926518 g, date of registration 06/01/23, unique ID 2020/1725.

摘要

目的

危重症 COVID-19 和非 COVID-19 患者均接受低分子肝素那屈肝素进行血栓预防。目前尚不清楚在这两组人群中,标准剂量是否足以达到目标抗 FXa 水平(0.20-0.50 IU/ml)。

方法

本研究是荷兰一家大型综合教学医院 ICU 进行的一项前瞻性观察性研究。纳入接受皮下给予 2850 IU、5700 IU 或 11400 IU 预防性剂量 LMWH 的 ICU 收治的 COVID-19 和非 COVID-19 患者。给药后 4 小时测定抗 FXa 水平。从电子健康记录系统中提取相关实验室参数、预设协变量和临床数据。主要目标是评估接受预防性剂量那屈肝素的危重症患者的抗 FXa 水平。次要目标是研究协变量是否对抗 FXa 水平有影响。

结果

共纳入 62 例患者进行分析。在 COVID-19 组和非 COVID-19 组中,分别有 29 例(96%)和 12 例(38%)患者的抗 FXa 水平超过 0.20 IU/ml。在非 COVID-19 组中,有 63%的患者抗 FXA 水平低于目标范围。在校正那屈肝素剂量后,体重与抗 FXa 水平之间存在显著关系(p=0.013)。

结论

在大多数研究患者群体中,危重症患者给予标准剂量 2850 IU 皮下注射那屈肝素不能达到目标抗 FXa 水平。我们建议使用标准较高的剂量,结合体重依赖性剂量,因为这可以使那屈肝素更好地暴露。

临床试验注册

回顾性注册,ClinicalTrials.gov ID NTC 05926518,注册日期 2023 年 6 月 1 日,唯一识别码 2020/1725。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2c9/10848501/ff9393ce005c/40360_2024_733_Fig1_HTML.jpg

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