The Stellenbosch team is pleased to report that Resia Pretorius, with support from the WE&ME Foundation (formerly TEMPI Foundation) through the PolyBio Research Foundation in the US, recruited a talented doctoral student, Jean Massimo Nunes, in November 2021. The team was supported by Retha Viviers, founder of the South African ME/CFS Foundation, and participants associated with the foundation.
The research was conducted after blood samples were taken in January 2022. The team is currently analyzing the blood samples using proteomics.
The following summary describes the results of a small preliminary study involving 25 participants with ME/CFS.
The occurrence of hyperactivated platelets and fibrin microclots in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)
Jean M Nunes, Arneaux Kruger, Amy Proal, Douglas B Kell, Etheresia Pretorius
Abstract
We have previously demonstrated that platelet-poor plasma (PPP) from patients with LongCovid/Post-Acute Sequelae of COVID-19 (PASC) is characterized by a hypercoagulable state, manifested by hyperactivated platelets and the presence of a substantial number of fibrin(ogen)amyloid microclumps or fibrinal microclumps. Given the significant overlap in symptoms and etiology between PASC and ME/CFS, we investigated whether coagulopathies, platelet hyperactivation, and/or fibrinamyloid formation differ between individuals with ME/CFS and age-matched, sex- and sex-matched healthy controls. Statistically, ME/CFS patients were far more hypercoagulable, as shown by thromboelastography of whole blood and platelet-poor plasma. The area of plasma images containing fibrinal microclumps was frequently more than 10 times larger in untreated platelet-poor plasma from individuals with ME/CFS than in healthy controls. A similar difference was observed when plasma samples were treated with thrombin. Using fluorescently labeled PAC-1, which recognizes glycoprotein IIb/IIIa, and CD62P, which binds P-selectin, we observed massive platelet hyperactivation and proliferation in samples from individuals with ME/CFS. Using a quantitative scoring system, this was assessed with a score of 2.72 ± 1.24 compared to 1.00 (activation with pseudopodia formation) in healthy controls. We conclude that ME/CFS is associated with significant and measurable alterations in coagulation, platelet hyperactivation, and fibrinal microclump formation. However, the fibrinal microclump burden was not as pronounced as previously observed in PASC. In particular, fibrinal microclumps can explain many of the symptoms, such as fatigue, experienced by patients with ME/CFS by (temporarily) blocking microcapillaries and thus causing ischemia. The discovery of these biomarkers, which indicate significant and systemic endothelial inflammation, represents an important development in ME/CFS research. It also points to new treatment strategies utilizing known medications and/or supplements that target systemic vascular pathology and endothelial inflammation.
1Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, Private Bag X1 Matieland, 7602, South Africa;
2 PolyBio Research Foundation, 7900 SE 28th ST, Suite 412, Mercer Island, WA 98040
Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, L69 7ZB, UK.
4The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kemitorvet 200, 2800 Kgs Lyngby, Denmark
