Institute of Cardiovascular Science, Haemostasis Research Unit, University College London (UCL), London, United Kingdom.
Department of Respiratory Medicine, University College London Hospitals NHS Foundation Trust, London, United Kingdom.
J Thromb Haemost. 2023 Jan;21(1):94-100. doi: 10.1016/j.jtha.2022.10.013. Epub 2022 Dec 22.
Post-COVID syndrome (PCS) affects millions of people worldwide, causing a multitude of symptoms and impairing quality of life months or even years after acute COVID-19. A prothrombotic state has been suggested; however, underlying mechanisms remain to be elucidated.
To investigate thrombogenicity in PCS using a microfluidic assay, linking microthrombi, thrombin generation, and the von Willebrand factor (VWF):a Disintegrin and Metalloproteinase with a Thrombospondin Type 1 motif, member 13 (ADAMTS13) axis.
Citrated blood was perfused through microfluidic channels coated with collagen or an antibody against the VWF A3 domain, and thrombogenicity was monitored in real time. Thrombin generation assays were performed and α(2)-antiplasmin, VWF, and ADAMTS13 activity levels were also measured.
We investigated thrombogenicity in a cohort of 21 patients with PCS with a median time following symptoms onset of 23 months using a dynamic microfluidic assay. Our data show a significant increase in platelet binding on both collagen and anti-VWF A3 in patients with PCS compared with that in controls, which positively correlated with VWF antigen (Ag) levels, the VWF(Ag):ADAMTS13 ratio (on anti-VWF A3), and inversely correlated with ADAMTS13 activity (on collagen). Thrombi forming on collagen presented different geometries in patients with PCS vs controls, with significantly increased thrombi area mainly attributable to thrombi length in the patient group. Thrombi length positively correlated with VWF(Ag):ADAMTS13 ratio and thrombin generation assay results, which were increased in 55.5% of patients. α(2)-Antiplasmin levels were normal in 89.5% of patients.
Together, these data present a dynamic assay to investigate the prothrombotic state in PCS, which may help unravel the mechanisms involved and/or establish new therapeutic strategies for this condition.
新冠后综合征（PCS）影响着全球数以百万计的人，在急性 COVID-19 后数月甚至数年，导致多种症状出现并降低生活质量。有人提出了一种促血栓形成状态；然而，其潜在机制仍有待阐明。
使用微流控测定法研究 PCS 的血栓形成能力，将微血栓、凝血酶生成和血管性血友病因子（VWF）：解整合素和金属蛋白酶与血小板反应蛋白 1 型基序 13（ADAMTS13）轴联系起来。
用包被有胶原蛋白或抗 VWF A3 结构域抗体的微流控通道灌注枸橼酸盐血液，并实时监测血栓形成能力。还进行了凝血酶生成测定，并测量了 α(2)-抗纤溶酶、VWF 和 ADAMTS13 活性水平。
我们使用动态微流控测定法研究了 21 名 PCS 患者的血栓形成能力，这些患者的症状发作后中位数时间为 23 个月。与对照组相比，我们的数据显示 PCS 患者的血小板在胶原蛋白和抗 VWF A3 上的结合显著增加，且与 VWF 抗原（Ag）水平、VWF(Ag):ADAMTS13 比值（在抗 VWF A3 上）呈正相关，与 ADAMTS13 活性（在胶原蛋白上）呈负相关。在 PCS 患者中，在胶原蛋白上形成的血栓具有与对照组不同的几何形状，主要由于患者组中的血栓长度增加，血栓面积显著增加。血栓长度与 VWF(Ag):ADAMTS13 比值和凝血酶生成试验结果呈正相关，在 55.5%的患者中增加。89.5%的患者的α(2)-抗纤溶酶水平正常。
这些数据共同提供了一种动态测定法来研究 PCS 中的促血栓形成状态，这可能有助于揭示所涉及的机制，并/或为这种情况建立新的治疗策略。
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