The potential role of ischaemia-reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications. — CFSMEATLAS
The potential role of ischaemia-reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications.
Kell, Douglas B, Pretorius, Etheresia · The Biochemical journal · 2022 · DOI
Quick Summary
This paper proposes that ME/CFS, Long COVID, and some other chronic diseases may be caused by a harmful cycle involving tiny blood clots blocking small blood vessels, followed by damage when blood flow returns. The authors suggest that this process creates harmful molecules called free radicals and triggers inflammation and other problems. They review existing evidence that treatments like antioxidants, anti-inflammatory drugs, and blood thinners might help address these underlying mechanisms.
Why It Matters
Understanding potential underlying biological mechanisms in ME/CFS is crucial for developing targeted treatments. If microclots and ischaemia-reperfusion injury contribute to ME/CFS pathology, this could explain why patients experience post-exertional malaise and suggest specific, mechanism-based therapeutic strategies that might be tested in clinical trials.
Observed Findings
Fibrin amyloid microclots have been detected in blood samples from patients with Long COVID and may block capillaries
Reactive oxygen species are produced during reoxygenation following hypoxic periods
Mast cell activation, oxidative stress markers, and hyperinflammatory responses have been documented in chronic inflammatory conditions including ME/CFS
Post-exertional malaise patterns are consistent with exercise-induced ischaemia-reperfusion cycles in capillaries
Inferred Conclusions
Ischaemia-reperfusion injury initiated by microclot formation may be a common pathological mechanism underlying ME/CFS, Long COVID, and some other chronic inflammatory diseases
The cycle of capillary blockage followed by reperfusion could mechanistically explain both fatigue/breathlessness and post-exertional malaise
Antioxidants, anti-inflammatory agents, iron chelators, and anticoagulants represent potential therapeutic approaches targeting the proposed mechanisms
Remaining Questions
Do fibrin microclots directly cause the hypoxia-reoxygenation cycles proposed in ME/CFS, or are they an associated finding?
Which therapeutic interventions (antioxidants, anticoagulants, fibrinolytics, or others) would be most effective, and what are appropriate doses and safety profiles for ME/CFS patients?
What This Study Does Not Prove
This is a theoretical review that does not present new experimental evidence or prove that microclots directly cause ME/CFS. The proposed mechanisms remain mechanistic hypotheses that require validation through prospective studies, biomarker research, and clinical trials. Correlation between proposed mechanisms and disease symptoms does not establish causation.