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使用患者血液进行体外研究,探讨纤维蛋白原 γ 链肽包裹的 ADP 包封脂质体对体外循环后凝血障碍的影响。

In vitro study on the effect of fibrinogen γ-chain peptide-coated ADP-encapsulated liposomes on postcardiopulmonary bypass coagulopathy using patient blood.

机构信息

Department of Cardiovascular Surgery, National Defense Medical College, Tokorozawa, Japan.

Department of Physiology, National Defense Medical College, Tokorozawa, Japan.

出版信息

J Thromb Haemost. 2023 Jul;21(7):1934-1942. doi: 10.1016/j.jtha.2023.03.018. Epub 2023 Mar 28.

DOI:10.1016/j.jtha.2023.03.018
PMID:36990156
Abstract

BACKGROUND

Fibrinogen γ-chain peptide-coated, adenosine 5'-diphosphate (ADP)-encapsulated liposomes (H12-ADP-liposomes) are potent hemostatic adjuvants that promote platelet thrombi formation at bleeding sites. Although we have reported the efficacy of these liposomes in a rabbit model of cardiopulmonary bypass coagulopathy, we are yet to address the possibility of their hypercoagulative potential, especially in human beings.

OBJECTIVES

Considering its future clinical applications, we herein investigated the safety of using H12-ADP-liposomes in vitro using blood samples from patients who had received platelet transfusion after cardiopulmonary bypass surgeries.

METHODS

Ten patients receiving platelet transfusions after cardiopulmonary bypass surgery were enrolled. Blood samples were collected at the following 3 points: at the time of incision, at the end of the cardiopulmonary bypass, and immediately after platelet transfusion. After incubating the samples with H12-ADP-liposomes or phosphate-buffered saline (PBS, as a control), blood coagulation, platelet activation, and platelet-leukocyte aggregate formation were evaluated.

RESULTS

Patients' blood incubated with H12-ADP-liposomes did not differ from that incubated with PBS in coagulation ability, degree of platelet activation, and platelet-leukocyte aggregation at any of the time points.

CONCLUSION

H12-ADP-liposomes did not cause abnormal coagulation, platelet activation, or platelet-leukocyte aggregation in the blood of patients who received platelet transfusion after a cardiopulmonary bypass. These results suggest that H12-ADP-liposomes could likely be safely used in these patients, providing hemostasis at the bleeding sites without causing considerable adverse reactions. Future studies are needed to ensure robust safety in human beings.

摘要

背景

纤维蛋白原 γ 链肽包被的、腺苷 5'-二磷酸(ADP)包封的脂质体(H12-ADP-脂质体)是有效的止血佐剂,可促进出血部位血小板血栓形成。虽然我们已经在心肺旁路体外循环凝血障碍的兔模型中报告了这些脂质体的疗效,但我们尚未确定其高凝潜能的可能性,尤其是在人类中。

目的

考虑到其未来的临床应用,我们在此使用接受心肺旁路手术后血小板输注的患者的血液样本,在体外研究了使用 H12-ADP-脂质体的安全性。

方法

纳入 10 名接受心肺旁路手术后血小板输注的患者。在以下 3 个时间点采集血液样本:切开时、心肺旁路结束时和血小板输注后立即。将样本与 H12-ADP-脂质体或磷酸盐缓冲盐水(PBS,作为对照)孵育后,评估血液凝固、血小板活化和血小板-白细胞聚集体形成。

结果

患者血液与 H12-ADP-脂质体孵育的凝血能力、血小板活化程度和血小板-白细胞聚集体形成在任何时间点均与与 PBS 孵育的血液无差异。

结论

H12-ADP-脂质体在接受心肺旁路手术后血小板输注的患者血液中不会引起异常凝血、血小板活化或血小板-白细胞聚集。这些结果表明,H12-ADP-脂质体可能在这些患者中安全使用,在出血部位提供止血作用而不会引起明显的不良反应。需要进一步的研究以确保在人类中具有稳健的安全性。

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引用本文的文献

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