Nunes Jean M, Kruger Arneaux, Proal Amy, Kell Douglas B, Pretorius Etheresia
Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch 7602, South Africa.
PolyBio Research Foundation, 7900 SE 28th ST, Suite 412, Mercer Island, WA 98040, USA.
Pharmaceuticals (Basel). 2022 Jul 27;15(8):931. doi: 10.3390/ph15080931.
We have previously demonstrated that platelet-poor plasma (PPP) obtained from patients with Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is characterized by a hypercoagulable state and contains hyperactivated platelets and considerable numbers of already-formed amyloid fibrin(ogen) or fibrinaloid microclots. Due to the substantial overlap in symptoms and etiology between Long COVID/PASC and ME/CFS, we investigated whether coagulopathies reflected in Long COVID/PASC-hypercoagulability, platelet hyperactivation, and fibrinaloid microclot formation-were present in individuals with ME/CFS and gender- and age-matched healthy controls. ME/CFS samples showed significant hypercoagulability as judged by thromboelastography of both whole blood and platelet-poor plasma. The area of plasma images containing fibrinaloid microclots was commonly more than 10-fold greater in untreated PPP from individuals with ME/CFS than in that of healthy controls. A similar difference was found when the plasma samples were treated with thrombin. Using fluorescently labelled PAC-1, which recognizes glycoprotein IIb/IIIa, and CD62P, which binds P-selectin, we observed hyperactivation of platelets in ME/CFS hematocrit samples. Using a quantitative scoring system, the ME/CFS platelets were found to have a mean spreading score of 2.72 ± 1.24 vs. 1.00 (activation with pseudopodia formation) for healthy controls. We conclude that ME/CFS is accompanied by substantial and measurable changes in coagulability, platelet hyperactivation, and fibrinaloid microclot formation. However, the fibrinaloid microclot load was not as great as was previously noted in Long COVID/PASC. Fibrinaloid microclots, in particular, may contribute to many ME/CFS symptoms, such as fatigue, seen in patients with ME/CFS, via the (temporary) blockage of microcapillaries and hence ischemia. Furthermore, fibrinaloid microclots might damage the endothelium. The discovery of these biomarkers represents an important development in ME/CFS research. It also points to possible uses for treatment strategies using known drugs and/or nutraceuticals that target systemic vascular pathology and endothelial inflammation.
我们之前已经证明，从患有长期新冠/新冠后急性后遗症（PASC）的患者中获得的乏血小板血浆（PPP）具有高凝状态的特征，并且含有过度活化的血小板以及大量已形成的淀粉样纤维蛋白（原）或类纤维蛋白微凝块。由于长期新冠/PASC与肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）在症状和病因上有很大重叠，我们研究了ME/CFS患者以及性别和年龄匹配的健康对照中是否存在长期新冠/PASC中所反映的凝血病——高凝性、血小板过度活化和类纤维蛋白微凝块形成。通过全血和乏血小板血浆的血栓弹力图评估，ME/CFS样本显示出显著的高凝性。来自ME/CFS患者的未经处理的PPP中，含有类纤维蛋白微凝块的血浆图像面积通常比健康对照者的大10倍以上。当血浆样本用凝血酶处理时也发现了类似的差异。使用识别糖蛋白IIb/IIIa的荧光标记PAC-1和结合P-选择素的CD62P，我们观察到ME/CFS血细胞比容样本中的血小板过度活化。使用定量评分系统，发现ME/CFS患者的血小板平均铺展评分为2.72±1.24，而健康对照者为1.00（形成伪足激活）。我们得出结论，ME/CFS伴有凝血性、血小板过度活化和类纤维蛋白微凝块形成方面的显著且可测量的变化。然而，类纤维蛋白微凝块负荷不如之前在长期新冠/PASC中所观察到的那么大。特别是，类纤维蛋白微凝块可能通过（暂时）阻塞微毛细血管从而导致局部缺血，进而导致ME/CFS患者出现许多症状，如疲劳。此外，类纤维蛋白微凝块可能会损伤内皮。这些生物标志物的发现代表了ME/CFS研究中的一项重要进展。它还指出了使用针对全身血管病变和内皮炎症的已知药物和/或营养保健品的治疗策略的可能用途。
