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

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.

Immunosuppression and Chagas disease: a management challenge.

Immunosuppression, which has become an increasingly relevant clinical condition in the last 50 years, modifies the natural history of Trypanosoma cruzi infection in most patients with Chagas disease. The main goal in this setting is to prevent the consequences of reactivation of T. cruzi infection by close monitoring. We analyze the relationship between Chagas disease and three immunosuppressant conditions, including a description of clinical cases seen at our center, a brief review of the literature, and recommendations for the management of these patients based on our experience and on the data in the literature. T. cruzi infection is considered an opportunistic parasitic infection indicative of AIDS, and clinical manifestations of reactivation are more severe than in acute Chagas disease. Parasitemia is the most important defining feature of reactivation. Treatment with benznidazole and/or nifurtimox is strongly recommended in such cases. It seems reasonable to administer trypanocidal treatment only to asymptomatic immunosuppressed patients with detectable parasitemia, and/or patients with clinically defined reactivation. Specific treatment for Chagas disease does not appear to be related to a higher incidence of neoplasms, and a direct role of T. cruzi in the etiology of neoplastic disease has not been confirmed. Systemic immunosuppressive diseases or immunosuppressants can modify the natural course of T. cruzi infection. Immunosuppressive doses of corticosteroids have not been associated with higher rates of reactivation of Chagas disease. Despite a lack of evidence-based data, treatment with benznidazole or nifurtimox should be initiated before immunosuppression where possible to reduce the risk of reactivation. Timely antiparasitic treatment with benznidazole and nifurtimox (or with posaconazole in cases of therapeutic failure) has proven to be highly effective in preventing Chagas disease reactivation, even if such treatment has not been formally incorporated into management protocols for immunosuppressed patients. International consensus guidelines based on expert opinion would greatly contribute to standardizing the management of immunosuppressed patients with Chagas disease.

Hypercoagulability biomarkers in Trypanosoma cruzi -infected patients.

There is a current controversy over the hypothesis that a number of thromboembolic events could be related to hypercoagulable state in patients with chronic Chagas disease. This study was designed to determine whether a prothrombotic state existed in chronic Trypanosoma cruzi-infected patients and, if so, to describe its evolution after treatment with Benznidazole. Twenty-five patients with chronic Chagas disease and 18 controls were evaluated. The markers used were prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin, plasminogen, protein C, total protein S, free protein S, factor VIII, D-dimer, activated factor VIIa, tissue-type plasminogen activator inhibitor-1, prothrombin fragment 1+2 (F1+2), plasmin-antiplasmin complexes, soluble P-selectin and endogenous thrombin potential (ETP). Despite statistically significant differences between cases and controls in several markers, only ETP (which quantifies the ability of plasma to generate thrombin when activated through tissue factor addition) (p<0.0001) and F1+2 (a marker of thrombin generation in vivo) (p<0.0001) showed values outside the normal levels in patients compared with controls. Similar results were obtained in these markers six months after treatment in the cohort of cases (p<0.0008 and p<0.004, respectively). These results may be relevant in clinical practice. Though current treatment for Chagas disease is still controversial, if it were considered as a thromboembolic risk factor the antiparasitic treatment strategy could be reinforced. The results also support further research on haemostasis parameters as candidates for early surrogate biomarkers of cure or progression of Chagas disease.