Altered Hypercoagulability Factors in Patients with Chronic Chagas Disease: Potential Biomarkers of Therapeutic Response.
Altered Hypercoagulability Factors in Patients with Chronic Chagas Disease: Potential Biomarkers of Therapeutic Response.
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DOI：
10.1371/journal.pntd.0004269
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发表时间：
2016-01
影响因子：
3.8
通讯作者：
Gascon J
中科院分区：
文献类型：
--
作者：
Pinazo MJ;Posada Ede J;Izquierdo L;Tassies D;Marques AF;de Lazzari E;Aldasoro E;Muñoz J;Abras A;Tebar S;Gallego M;de Almeida IC;Reverter JC;Gascon J
在没有心肌病的恰加斯病患者中描述了血栓栓塞事件。我们的目的是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早期正常化。来自恰加斯病流行地区的 99 名个体被分为两组：G1，感染克氏锥虫（n = 56）；G1，感染克氏锥虫（n = 56）； G2，健康个体（n = 43）。在基线时测量了二十四个止血因素。接受苯并硝唑治疗的 G1 期患者随访 36 个月，每 6 个月就诊一次，记录临床参数和常规血清学、化学发光酶联免疫吸附测定（锥鞭毛体衍生的糖基磷脂酰肌醇锚定粘蛋白）、定量聚合酶链反应和止血试验的表现。基线时，77% 和 50% 的感染患者凝血酶原片段 1+2 (F1+2) 和内源性凝血酶电位 (ETP) 表达异常，但在治疗后不久分别有 76% 和 96% 的病例恢复并保持在正常水平。 32% 的 G1 期患者的纤溶酶-抗纤溶酶复合物 (PAP) 在治疗前发生改变，但 94% 的病例在治疗几个月后恢复正常。随访期间 F1+2 值正常的患者均未出现 qRT-PCR 结果阳性，但 ETP 值正常的患者中有 3/24 (13%) 出现阳性。在接受苯并硝唑治疗的慢性克氏锥虫感染患者中，一定比例的凝血标志物改变后恢复到正常水平。 F1+2、ETP 和 PAP 可能是评估苯并硝唑持续反应的有用标记。该手稿描述了一项研究的结果，该研究的目的是通过研究几种凝血因子来评估拉丁美洲常见的寄生虫感染（称为克氏锥虫感染或恰加斯病）患者的凝血倾向。根据本主题的最新技术，建议在感染的近期（急性）和晚期（慢性）阶段针对恰加斯病进行特定治疗。由于各研究结果不一致以及缺乏对特定治疗反应的早期可测量参数，当前可用药物在慢性感染阶段的有效性仍然是一个争论的话题。这项研究的另一个目的是确定克氏锥虫感染者血浆中促凝血活性上调的存在是否可以用作指示处于该疾病慢性阶段的人的治疗反应的潜在标志物。这项研究的结果表明，测量促凝血活性的变化可能有助于指示对克氏锥虫慢性感染患者的具体治疗以及有关治疗生物标志物早期反应的新数据。
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. The manuscript describes the results of a study whose aim was to assess the tendency to coagulate in people suffering from a parasitic infection frequent in Latin America named T. cruzi infection or Chagas disease, by the study of several coagulation factors. According to the state of the art in this topic, specific treatment for Chagas disease is recommended in recent (acute) and late (chronic) stages of the infection. The effectiveness of current available drugs in the chronic stage of infection is still a topic of debate due to inconsistent results across studies and a lack of early measurable parameters of response to specific treatment. Another aim of this study was to determine if the presence of an upregulated procoagulative activity in plasma in people suffering T. cruzi infection could be used as potential marker that indicates therapeutic response in people at chronic stage of the disease. The results of this study suggest that measurements of alterations of procoagulative activity may be useful to indicate specific treatment for T. cruzi chronically infected patients and new data concerning early response to treatment biomarkers.