Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden.
Thromb Res. 2024 Nov;243:109135. doi: 10.1016/j.thromres.2024.109135. Epub 2024 Aug 30.
Despite medical interventions, COVID-19 continues to persist at pandemic proportions. A hypercoagulation state was rapidly observed in the severely ill, and the incidence of thromboembolic events remains elevated. Interleukin inhibitors have demonstrated positive effects on the hyperactivation of the immune system in COVID-19, with the interleukin-6 inhibitor tocilizumab showing promising results in reducing mortality. Nevertheless, the impact of interleukin inhibitors on the coagulation system remains incompletely understood.
In this clinical trial conducted in Stockholm, Sweden, interleukin inhibitors, namely anakinra (ANA) or tocilizumab (TOCI), were randomly administered in addition to standard care (SC) to hospitalized patients with COVID-19. A control group received only SC. The primary outcome sought to measure effects on global hemostasis, as indicated by changes in functional coagulation tests, specifically Rotational Thromboelastometry (ROTEM) or Overall Hemostatic Potential (OHP), visualized through scanning electron microscopy images. Secondary outcomes included effects on conventional coagulation laboratory tests.
The study enrolled 74 patients who were randomized to receive either ANA or TOCI in addition to SC, or SC alone. In the TOCI group, ROTEM variables exhibited less hypercoagulation after 29 days compared with ANA or SC treatment groups, characterized by prolonged clot formation time and decreased clot firmness. OHP decreased, but there were no significant differences among the three treatment groups. Plasma fibrinogen levels, initially elevated, decreased significantly in TOCI recipients over time.
Tocilizumab treatment demonstrated a significant reduction of hypercoagulation in hospitalized COVID-19 patients, by improvements in both global coagulation tests and conventional laboratory tests, in comparison with anakinra or SC alone. This finding underscores the significance of tocilizumab as a viable treatment option in severe COVID-19 cases, with the potential to decrease thrombosis incidence.
尽管采取了医疗干预措施，COVID-19 仍持续以大流行的规模存在。严重疾病患者迅速出现高凝状态，血栓栓塞事件的发生率仍然居高不下。白细胞介素抑制剂已证明对 COVID-19 中免疫系统的过度激活具有积极作用，白细胞介素-6 抑制剂托珠单抗在降低死亡率方面显示出良好的效果。然而，白细胞介素抑制剂对凝血系统的影响仍不完全清楚。
在瑞典斯德哥尔摩进行的这项临床试验中，白细胞介素抑制剂，即阿那白滞素（ANA）或托珠单抗（TOCI），除了标准治疗（SC）外，还被随机给予 COVID-19 住院患者。对照组仅接受 SC。主要结局旨在通过功能凝血试验（特别是旋转血栓弹性测定法（ROTEM）或整体止血潜能（OHP））的变化来衡量对整体止血的影响，这些变化通过扫描电子显微镜图像进行可视化。次要结局包括对常规凝血实验室检测的影响。
该研究纳入了 74 名患者，他们被随机分为接受 ANA 或 TOCI 加 SC 或 SC 单独治疗的三组。在 TOCI 组中，与 ANA 或 SC 治疗组相比，ROTEM 变量在 29 天后表现出较低的高凝状态，表现为凝血形成时间延长和凝血强度降低。OHP 下降，但三组之间无显著差异。血浆纤维蛋白原水平最初升高，随着时间的推移，TOCI 组患者的水平显著下降。
与单独使用阿那白滞素或 SC 相比，托珠单抗治疗可显著降低住院 COVID-19 患者的高凝状态，改善整体凝血试验和常规实验室检测结果。这一发现强调了托珠单抗作为严重 COVID-19 病例的一种可行治疗选择的重要性，有可能降低血栓形成的发生率。
