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

Date Published: January 4, 2016

Publisher: Public Library of Science

Author(s): Maria-Jesus Pinazo, Elizabeth de Jesus Posada, Luis Izquierdo, Dolors Tassies, Alexandre-Ferreira Marques, Elisa de Lazzari, Edelweiss Aldasoro, Jose Muñoz, Alba Abras, Silvia Tebar, Montserrat Gallego, Igor Correia de Almeida, Joan-Carles Reverter, Joaquim Gascon, Rodrigo Correa-Oliveira.

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.

Partial Text: Chagas disease (CD) is one of 17 neglected tropical diseases recognized by the World Health Organization. Caused by the protozoan parasite Trypanosoma cruzi, it mainly affects people with poor socioeconomic status and limited health care access in endemic and nonendemic countries. [1, 2]

Ninety-nine individuals (76 women) were studied. Fifty-six of these (43 women) were T.cruzi–positive (G1) and 43 (33 women) were T.cruzi–negative. The mean ages were 34 (SD, 9) years for the overall group (range 17–56, median 33), 37 (SD, 9) years for G1, and 32 (SD, 7) years for G2. Fifty G1 patients were treated with benznidazole (six were lost to follow-up before starting treatment due to unexpected work-related changes in the migratory process). Forty-five (90%) completed treatment. Eighty-six participants (87%) (51 [91%] in G1 and 35 [81%] in G2) were from Bolivia. None of the participants traveled to their countries or other CD-endemic areas during follow-up. The clinical and demographic data are summarized in Table 1. The epidemiological and baseline clinical data were similar in both groups, making them statistically comparable.



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