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依诺肝素对急性肺栓塞患者血浆纤维蛋白凝块特性和纤维蛋白结构的影响。

Effect of enoxaparin on plasma fibrin clot properties and fibrin structure in patients with acute pulmonary embolism.

机构信息

Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland; John Paul II Hospital, Krakow, Poland.

Faculty of Health Sciences, Jagiellonian University Medical College, Krakow, Poland.

出版信息

Vascul Pharmacol. 2020 Oct-Nov;133-134:106783. doi: 10.1016/j.vph.2020.106783. Epub 2020 Aug 22.

Abstract

BACKGROUND

Low-molecular-weight heparins (LMWHs) influence the fibrin network structure in in vitro models. There have been no reports on LMWH-induced modifications of fibrin clot characteristics and their determinants in acute pulmonary embolism (PE).

AIM

We investigated how enoxaparin alters fibrin clot properties in acute PE patients.

METHODS

Clots were generated from plasma of 46 acute PE patients, aged 47-77 years treated with enoxaparin 1 mg/kg bid. Fibrin clot permeability (K) and clot lysis time (CLT), along with coagulation and fibrinolysis proteins were determined. Plasma fibrin clot nanostructure was assessed using scanning electron microscopy (SEM).

RESULTS

Both K and CLT were associated with anti-factor (F)Xa activity (r = 0.75, p < 0.0001 and r = -0.37, p = 0.011). Anti-FXa was positively associated with fibrin fiber diameter and the pore area, and inversely with fibrin fiber density on SEM images. Multiple regression analysis adjusted for age, body-mass index, and fibrinogen levels showed that anti-FXa activity, antithrombin activity, and FVIII activity determined K, while anti-FXa activity, plasminogen activator inhibitor-1 level, and presence of right ventricular dysfunction determined CLT.

CONCLUSIONS

We identified new laboratory and clinical factors contributing to prothrombotic plasma fibrin clot characteristics during enoxaparin treatment, which might help elucidate mechanisms underlying therapy failure in patients with acute PE.

摘要

背景

低分子肝素(LMWH)可影响体外模型中的纤维蛋白网络结构。目前尚无关于 LMWH 诱导急性肺栓塞(PE)患者纤维蛋白凝块特征改变及其决定因素的报道。

目的

我们研究了依诺肝素如何改变急性 PE 患者纤维蛋白凝块的特性。

方法

从年龄为 47-77 岁、接受依诺肝素 1mg/kg bid 治疗的 46 例急性 PE 患者的血浆中生成凝块。测定纤维蛋白凝块的通透性(K)和凝块溶解时间(CLT)以及凝血和纤溶蛋白。使用扫描电子显微镜(SEM)评估血浆纤维蛋白凝块的纳米结构。

结果

K 和 CLT 均与抗因子(F)Xa 活性相关(r=0.75,p<0.0001 和 r=-0.37,p=0.011)。抗-FXa 与纤维蛋白纤维直径和孔面积呈正相关,与 SEM 图像上的纤维蛋白纤维密度呈负相关。调整年龄、体重指数和纤维蛋白原水平的多元回归分析表明,抗-FXa 活性、抗凝血酶活性和 FVIII 活性决定 K,而抗-FXa 活性、纤溶酶原激活物抑制剂-1 水平和右心室功能障碍的存在决定 CLT。

结论

我们发现了新的实验室和临床因素,这些因素有助于解释依诺肝素治疗期间促血栓形成的血浆纤维蛋白凝块特征,这可能有助于阐明急性 PE 患者治疗失败的机制。

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