Abstract
Re. Re.: “Immunothrombotic dysregulation in Chagas disease (CD) and COVID-19: a comparative study of anticoagulation”: In the commentary on our paper, Hasslocher-Moreno made the point that indeterminate and digestive forms are not related to thromboembolic events, only thrombogenic alterations occur in CD with cardiopathy, however there is indirect evidence related to thombotic alterations, such as cerebral thrombosis. Our assertion is based on previous data discussed in this letter.
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Dear Editor,
In the commentary on our paper [1], Hasslocher-Moreno [2] made the point that it is incorrect that indeterminate and digestive forms are not related to thromboembolic events and these events occur only in Chagas disease (CD) with cardiopathy. Our assumption is based on previous data in subjects with asymptomatic CD, which reported an increased prothrombin fragment 1 + 2, d-dimer, PAI-1, tissue factor pathway inhibitor antibodies (aTFPI), fibrinogen, ATM complex (T/IXa/Xa/Xia-AT), and degradation products of the fibrinogen/fibrin [3, 4]. Even though the results are inconclusive, there is still a strong evidence that in subjects with CD and without cardiomyopathy, the treatment with benznidazole reduces the hypercoagulable state. In particular, it decreases prothrombin fragment 1 + 2 (F1 + 2) and endogenous thrombin potential (ETP) [5, 6].
It is not known whether there are hypercoagulant mechanisms involve in the esophagus and/or intestine in indeterminate forms for CD. However, there is indirect evidence that in other clinical form of CD such as meningoencephalitis [7], the prothrombogenic activity may be present through an increase of neutrophil extracellular traps (NETs).
In the central nervous systems, there is increase in NETs of rats [8], dogs, and common possums, infected by Trypanosoma cruzi (T. cruzi) [9]. It is known that soluble molecules of T. cruzi stimulate neutrophils, resulting in the formation of NETs [10]. These are composed of DNA, histones, and elastase, which are promoters of immunothrombosis [11, 12]. In addition, NETs are recognized in different intestinal pathologies with disorders inflammatory that promote thrombosis and facilitate cancer progression [13].
Therefore, it cannot be ruled out that patients with CD, presenting with megaoesophagus or megacolon, do not have hypercoagulability. Specific studies are required in this pathology. More information on microthrombosis and endotheliopathy in CD is found in our work [1].
Data availability
The data can be obtained upon request to the corresponding author.
References
Pérez-Campos Mayoral L, Hernández-Huerta MT, Papy-García D, Barritault D, Zenteno E, Sánchez Navarro LM, Pérez-Campos Mayoral E, Matias Cervantes CA, Martínez Cruz M, Mayoral Andrade G, López Cervantes M, Vázquez Martínez G, López Sánchez C, Pina Canseco S, Martínez Cruz R, Pérez-Campos E (2021) Immunothrombotic dysregulation in chagas disease and COVID-19: a comparative study of anticoagulation. Mol Cell Biochem 476(10):3815–3825. https://doi.org/10.1007/s11010-021-04204-3
Hasslocher-Moreno AM (2022) Re: “Immunothrombotic dysregulation in chagas disease and COVID-19: a comparative study of anticoagulation.” Mol Cell Biochem. https://doi.org/10.1007/s11010-022-04361-z
Herrera RN, Díaz de Amaya EI, Pérez Aguilar RC, Joo Turoni C, Marañón R, Berman SG, Luciardi HL, Coviello A, Peral de Bruno M (2011) Inflammatory and prothrombotic activation with conserved endothelial function in patients with chronic, asymptomatic Chagas disease. Clin Appl Thromb Hemost 17(5):502–507. https://doi.org/10.1177/1076029610375814
Herrera RN, Diaz E, Perez Aguilar R, Bianchi J, Berman S, Luciardi HL (2005) Prothrombotic state in early stages of chronic Chagas’ disease. Its association with thrombotic risk factors. Arch Cardiol Mex 75(3):38–48
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 (2016) Altered hypercoagulability factors in patients with chronic Chagas disease: potential biomarkers of therapeutic response. PLoS Negl Trop Dis 10(1):e0004269. https://doi.org/10.1371/journal.pntd.0004269
Pinazo MJ, Tàssies D, Muñoz J, Fisa R, Posada Ede J, Monteagudo J, Ayala E, Gállego M, Reverter JC, Gascon J (2011) Hypercoagulability biomarkers in Trypanosoma cruzi-infected patients. Thromb Haemost 106(4):617–623. https://doi.org/10.1160/TH11-04-0251
Córdova E, Maiolo E, Corti M, Orduña T (2010) Neurological manifestations of Chagas’ disease. Neurol Res 32(3):238–244. https://doi.org/10.1179/016164110X12644252260637
Da Mata JR, Camargos MR, Chiari E, Machado CR (2000) Trypanosoma cruzi infection and the rat central nervous system: proliferation of parasites in astrocytes and the brain reaction to parasitism. Brain Res Bull 53(2):153–162. https://doi.org/10.1016/s0361-9230(00)00326-9
de Buhr N, Bonilla MC, Jimenez-Soto M, von Köckritz-Blickwede M, Dolz G (2018) Extracellular trap formation in response to Trypanosoma cruzi infection in granulocytes isolated from dogs and common opossums, natural reservoir hosts. Front Microbiol 9:966. https://doi.org/10.3389/fmicb.2018.00966
Sousa-Rocha D, Thomaz-Tobias M, Diniz LF, Souza PS, Pinge-Filho P, Toledo KA (2015) Trypanosoma cruzi and Its soluble antigens induce NET release by stimulating toll-like receptors. PLoS ONE 10(10):e0139569. https://doi.org/10.1371/journal.pone.0139569
Brill A, Fuchs TA, Savchenko AS, Thomas GM, Martinod K, De Meyer SF, Bhandari AA, Wagner DD (2012) Neutrophil extracellular traps promote deep vein thrombosis in mice. J Thromb Haemost 10(1):136–144. https://doi.org/10.1111/j.1538-7836.2011.04544.x
Shi Y, Gauer JS, Baker SR, Philippou H, Connell SD, Ariëns RAS (2021) Neutrophils can promote clotting via FXI and impact clot structure via neutrophil extracellular traps in a distinctive manner in vitro. Sci Rep 11(1):1718. https://doi.org/10.1038/s41598-021-81268-7
Chen K, Shao LH, Wang F, Shen XF, Xia XF, Kang X, Song P, Wang M, Lu XF, Wang C, Hu QY, Liu S, Guan WX (2021) Netting gut disease: neutrophil extracellular trap in intestinal pathology. Oxid Med Cell Longev 192021:5541222. https://doi.org/10.1155/2021/5541222
Funding
None.
Author information
Authors and Affiliations
Contributions
All authors contributed equally to the study conception and design. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors have declared no competing interests in this study.
Ethical approval
Not applicable.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Pérez-Campos Mayoral, L., Hernández-Huerta, M.T., Pérez-Campos Mayoral, E. et al. Re. Re.: “Immunothrombotic dysregulation in Chagas disease and COVID19: a comparative study of anticoagulation”. Mol Cell Biochem 478, 361–362 (2023). https://doi.org/10.1007/s11010-022-04511-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-022-04511-3