Coagulation disorders in Chagas disease: A pathophysiological systematic review and meta-analysis

Currently, Chagas disease (CD) constitutes one of the main public health problems in Latin America. However, little is known about potential mechanisms of disease different from cardiac or digestive involvement, such as the coagulation disorders elicited by the parasite persistence in the tissues. The aim of this systematic review was to describe and characterize all the published literature that evaluated the pathophysiological aspects of coagulation disorders in CD.

Searches in Medline, EMBASE, and LILACS databases (from inception to July 28th, 2020) were performed. Articles of any language reporting the levels of different coagulation factors/markers or the prevalence of abnormal levels of the mentioned molecules in patients with CD were included. Two reviewers independently selected the studies, extracted the data, and assessed the quality of evidence. Estimates were pooled using random-effects meta-analyses.

Seven studies evaluating a total of 676 participants fulfilled the criteria and were included, while only six were suitable for meta-analyzing (544 participants, 52% men, mean age: 49 ± 8 years). 57.16% of the patients in the meta-analysis had a serological confirmed diagnosis of CD, while 97% of these were in the indeterminate stage of the disease. Patients in the CD group had higher levels of F 1 + 2 (SMD 5.15. 95% CI 1.92, 8.38), PAI-1 (SMD 0.46. 95% CI 0.07; 0.89), and P-selectin (SMD 1.8; 95% CI 0.13-3.47) compared to healthy controls. Furthermore, benznidazole therapy was associated with a reduction in the levels of these biomarkers after treatment.

The results of the present study suggest that patients with chronic T. cruzi infection are affected by a potential hypercoagulable state irrespective of the development of cardiac or digestive disease. Furthermore, the reduction in the levels of the coagulation markers after benznidazole therapy may suggest a significant role of the parasite load in the development of these coagulation disorders. There is a scarcity of research assessing the molecular and pathophysiological mechanisms of coagulation disorders in Chagas disease. Further research is needed to assess the benefit of benznidazole therapy on this hypercoagulable state in the long-term, along with its impact on the risk of thromboembolic events in CD patients.