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慢性恰加斯病患者高凝性因子的改变:治疗反应的潜在生物标志物

Altered Hypercoagulability Factors in Patients with Chronic Chagas Disease: Potential Biomarkers of Therapeutic Response.

作者信息

Pinazo Maria-Jesus, Posada Elizabeth de Jesus, Izquierdo Luis, Tassies Dolors, Marques Alexandre-Ferreira, de Lazzari Elisa, Aldasoro Edelweiss, Muñoz Jose, Abras Alba, Tebar Silvia, Gallego Montserrat, de Almeida Igor Correia, Reverter Joan-Carles, Gascon Joaquim

机构信息

ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic- Universitat de Barcelona, Barcelona, Spain.

Hemotherapy and Hemostasis Department, Hospital Clínic de Barcelona, Barcelona, Spain.

出版信息

PLoS Negl Trop Dis. 2016 Jan 4;10(1):e0004269. doi: 10.1371/journal.pntd.0004269. eCollection 2016 Jan.

Abstract

Thromboembolic events were described in patients with Chagas disease without cardiomyopathy. We aim to confirm if there is a hypercoagulable state in these patients and to determine if there is an early normalization of hemostasis factors after antiparasitic treatment. Ninety-nine individuals from Chagas disease-endemic areas were classified in two groups: G1, with T.cruzi infection (n = 56); G2, healthy individuals (n = 43). Twenty-four hemostasis factors were measured at baseline. G1 patients treated with benznidazole were followed for 36 months, recording clinical parameters and performance of conventional serology, chemiluminescent enzyme-linked immunosorbent assay (trypomastigote-derived glycosylphosphatidylinositol-anchored mucins), quantitative polymerase chain reaction, and hemostasis tests every 6-month visits. Prothrombin fragment 1+2 (F1+2) and endogenous thrombin potential (ETP) were abnormally expressed in 77% and 50% of infected patients at baseline but returned to and remained at normal levels shortly after treatment in 76% and 96% of cases, respectively. Plasmin-antiplasmin complexes (PAP) were altered before treatment in 32% of G1 patients but normalized in 94% of cases several months after treatment. None of the patients with normal F1+2 values during follow-up had a positive qRT-PCR result, but 3/24 patients (13%) with normal ETP values did. In a percentage of chronic T. cruzi infected patients treated with benznidazole, altered coagulation markers returned into normal levels. F1+2, ETP and PAP could be useful markers for assessing sustained response to benznidazole.

摘要

在没有心肌病的恰加斯病患者中描述了血栓栓塞事件。我们旨在确认这些患者是否存在高凝状态,并确定抗寄生虫治疗后止血因子是否能早期恢复正常。来自恰加斯病流行地区的99人被分为两组:G1组为克氏锥虫感染患者(n = 56);G2组为健康个体(n = 43)。在基线时测量了24种止血因子。对接受苯硝唑治疗的G1组患者进行了36个月的随访,每6个月记录一次临床参数,并进行常规血清学、化学发光酶联免疫吸附测定(源自锥鞭毛体的糖基磷脂酰肌醇锚定粘蛋白)、定量聚合酶链反应和止血测试。在基线时,77%的感染患者凝血酶原片段1+2(F1+2)和内源性凝血酶潜力(ETP)异常表达,但分别在治疗后不久,76%和96%的病例中恢复并维持在正常水平。32%的G1组患者在治疗前纤溶酶 - 抗纤溶酶复合物(PAP)发生改变,但在治疗后几个月,94%的病例恢复正常。随访期间F1+2值正常的患者中,qRT-PCR结果均为阴性,但ETP值正常的24例患者中有3例(13%)结果为阳性。在接受苯硝唑治疗的一部分慢性克氏锥虫感染患者中,改变的凝血标志物恢复到正常水平。F1+2、ETP和PAP可能是评估对苯硝唑持续反应的有用标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87cc/4700971/fc10f909de47/pntd.0004269.g001.jpg

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