Triple Anticoagulant Therapy for Long COVID: A Comprehensive Overview
Long COVID, or Post-Acute Sequelae of COVID-19 (PASC), is a condition affecting millions globally, characterized by symptoms like chronic fatigue, cognitive dysfunction, and shortness of breath. A growing body of research highlights fibrin amyloid microclots and platelet hyperactivation as key factors in these symptoms. These microclots reduce oxygen transport at the cellular level, contributing to the debilitating nature of Long COVID. Addressing these underlying pathologies is essential for developing effective treatments.
Recent studies suggest that triple anticoagulant therapy, targeting hypercoagulability and abnormal clot formation, may be a promising approach for treating Long COVID. One such study from South Africa involved 91 patients diagnosed with Long COVID, many of whom reported no prior comorbidities before their initial COVID-19 infection. The treatment included a dual antiplatelet therapy (DAPT) regimen—comprising Clopidogrel (75 mg) and Aspirin (75 mg) daily—along with a direct oral anticoagulant (DOAC), Apixaban (5 mg twice daily). To prevent gastric side effects, patients were also given a proton pump inhibitor (PPI), pantoprazole (40 mg daily).
Treatment Findings and Symptom Resolution
The findings from the study showed significant symptom relief in most patients, alongside improvements in laboratory markers of fibrin amyloid microclots and platelet hyperactivation. Fatigue, cognitive dysfunction, and muscle and joint pain were among the most commonly reported symptoms that showed improvement. Fluorescence microscopy before and after treatment revealed a marked reduction in microclot formation and platelet activation.
The absence of serious bleeding events throughout the study suggests that this anticoagulant regimen is relatively safe under expert supervision. However, the authors stress that the therapy remains experimental and must be administered with caution due to potential bleeding risks.
Mechanisms of Action and Implications for Long COVID
The mechanism underlying Long COVID symptoms appears linked to widespread endothelial dysfunction and microvascular thrombosis, which impair oxygen delivery at the capillary level. By normalizing clotting physiology and reversing endothelial inflammation, the triple therapy effectively addresses these root causes. While these initial findings are encouraging, the authors urge that more rigorous, randomized controlled trials (RCTs) are needed to establish the safest and most effective combinations of drugs and treatment durations. Such trials will also help to quantify the risk of adverse events, especially the risk of bleeding, which is a significant concern with anticoagulant therapy.
Conclusion
Triple anticoagulant therapy represents a promising treatment option for Long COVID by targeting the fibrin amyloid microclots and platelet hyperactivation that contribute to the condition’s pathology. The study demonstrated symptom relief and a reduction in abnormal clot formation among most participants. However, due to the experimental nature of this treatment, it should only be administered by experienced physicians well-versed in clotting physiology and the specific abnormalities seen in Long COVID. Urgent clinical trials are necessary to further evaluate its safety, efficacy, and to optimize its clinical use, given the pressing need to manage the growing global burden of Long COVID.
This promising yet preliminary approach could offer significant hope for millions of people worldwide grappling with the long-term effects of COVID-19.
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