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抗磷脂综合征患者的纤维蛋白形成及纤溶功能研究。

Studies of fibrin formation and fibrinolytic function in patients with the antiphospholipid syndrome.

作者信息

Vikerfors Anna, Svenungsson Elisabet, Ågren Anna, Mobarrez Fariborz, Bremme Katarina, Holmström Margareta, Eelde Anna, Bruzelius Maria, Elgue Graciela, Wallén Håkan, Antovic Aleksandra

机构信息

Karolinska Institutet, Department of Medicine Solna, Unit of Rheumatology, Karolinska University Hospital, Stockholm, Sweden.

Karolinska Institutet, Department of Medicine Solna, Unit of Rheumatology, Karolinska University Hospital, Stockholm, Sweden.

出版信息

Thromb Res. 2014 May;133(5):936-44. doi: 10.1016/j.thromres.2014.02.023. Epub 2014 Feb 28.

Abstract

OBJECTIVE

The antiphospholipid syndrome (APS) is defined by persistent antiphospholipid antibodies together with thrombosis and/or pregnancy morbidity. We investigated the tightness of fibrin clot and fibrinolytic function in plasma samples from APS patients compared with two control groups.

MATERIAL AND METHODS

APS patients (n=49), healthy controls (HC) (n=19) and warfarin-treated nonAPS thrombosis controls (nonAPS-TC) (n=39) were investigated. Fibrin permeability was assessed as the permeability coefficient (Ks) by a flow measurement technique. Additionally, clot density and fibrinolytic function was analysed by a turbidimetric clotting and lysis assay. Fibrin structure was visualised using scanning electron microscopy. Finally, the number of cell-derived microparticles (MPs) in the samples were correlated to fibrin permeability

RESULTS AND CONCLUSIONS

The Ks value was lower in samples from APS-patients compared to HC and nonAPS-TC (p<0.0001 for both) indicating a less permeable fibrin clot in APS patients. Scanning electron microscopy images confirmed compact fibrin with smaller intrinsic pores and thinner fibers in samples from APS patients as compared to HC. Prolonged fibrinolysis (clot lysis) times were present in the subgroup of APS patients with previous arterial thrombosis (n=15) as compared to HC and to nonAPS-TC (all p-values<0.05). In conclusion, tighter fibrin clots were formed in plasma from APS patients compared with healthy controls and warfarin treated patients with thrombosis of "nonAPS origin". This new observation presents a possible mechanism contributing to the thrombotic predisposition of APS patients. Impaired fibrinolysis, selectively present among APS patients with previous arterial thrombosis, may further aggravate the pro-thrombotic state in this APS subgroup.

摘要

目的

抗磷脂综合征(APS)的定义为持续存在抗磷脂抗体并伴有血栓形成和/或妊娠并发症。我们研究了APS患者血浆样本中纤维蛋白凝块的紧密程度和纤维蛋白溶解功能,并与两个对照组进行比较。

材料与方法

研究对象包括APS患者(n = 49)、健康对照者(HC)(n = 19)和接受华法林治疗的非APS血栓形成对照者(非APS-TC)(n = 39)。通过流动测量技术将纤维蛋白通透性评估为通透系数(Ks)。此外,通过比浊法凝血和溶解试验分析凝块密度和纤维蛋白溶解功能。使用扫描电子显微镜观察纤维蛋白结构。最后,将样本中细胞衍生微粒(MPs)的数量与纤维蛋白通透性相关联。

结果与结论

与HC和非APS-TC相比,APS患者样本中的Ks值较低(两者p均<0.0001),表明APS患者的纤维蛋白凝块通透性较低。扫描电子显微镜图像证实,与HC相比,APS患者样本中的纤维蛋白致密,固有孔隙较小且纤维较细。与HC和非APS-TC相比,既往有动脉血栓形成的APS患者亚组(n = 15)的纤维蛋白溶解(凝块溶解)时间延长(所有p值<0.05)。总之,与健康对照者和接受华法林治疗的“非APS来源”血栓形成患者相比,APS患者血浆中形成的纤维蛋白凝块更紧密。这一新发现提出了一种可能导致APS患者血栓形成倾向的机制。在既往有动脉血栓形成的APS患者中选择性存在的纤维蛋白溶解受损,可能会进一步加重该APS亚组的血栓前状态。

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