Department of Medicine and Ageing Sciences, University G. D'Annunzio, Chieti-Pescara, Italy; Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
Department of Internal Medicine, "G. D'Annunzio" University, Chieti, Italy.
Eur J Intern Med. 2021 Jan;83:34-38. doi: 10.1016/j.ejim.2020.10.020. Epub 2020 Nov 3.
Many COVID-19 patients develop a hyperinflammatory response which activates blood coagulation and may contribute to the occurrence of thromboembolic complications. Blockade of interleukin-6, a key cytokine in COVID-19 pathogenesis, may improve the hypercoagulable state induced by inflammation. The aim of this study was to evaluate the effects of subcutaneous tocilizumab, a recombinant humanized monoclonal antibody against the interleukin-6 receptor on coagulation parameters.
Hospitalized adult patients with laboratory-confirmed moderate to critical COVID-19 pneumonia and hyperinflammation, who received a single 324 mg subcutaneous dose of tocilizumab on top of standard of care were enrolled in this analysis. Coagulation parameters were measured before tocilizumab and at day 1, 3, and 7 after treatment. All patients were followed-up for 35 days after admission or until death.
70 patients (mean age 60 years, interquartile range 52-75) were included. Treatment with tocilizumab was associated with a reduction in D-dimer levels (-56%; 95% confidence interval [CI], -68% to -44%), fibrinogen (-48%; 95%CI, -60% to -35%), C-reactive protein (-93%; 95%CI, -99% to -87%), prothrombin time (-4%; 95%CI,-9% to 0.8%), and activated thromboplastin time (-4%; 95%CI,-8.7% to 0.8%), and an increase in platelet count (34%; 95%CI, 23% to 45%). These changes occurred already one day after treatment with sustained reductions throughout day 7. The improvement in coagulation was consistently observed in patients receiving prophylactic or therapeutic dose anticoagulants, and was paralleled by a rapid improvement in respiratory function.
Subcutaneous tocilizumab was associated with significant improvement of blood coagulation parameters independently of thromboprophylaxis dose.
许多 COVID-19 患者会出现过度炎症反应，从而激活血液凝固，并可能导致血栓栓塞并发症的发生。阻断白细胞介素-6（COVID-19 发病机制中的关键细胞因子）可能会改善炎症引起的高凝状态。本研究旨在评估皮下注射托珠单抗（一种针对白细胞介素-6 受体的重组人源化单克隆抗体）对凝血参数的影响。
这项分析纳入了在接受标准治疗的基础上接受单次 324mg 皮下托珠单抗治疗的、实验室确诊的中度至重症 COVID-19 肺炎和过度炎症的住院成年患者。在托珠单抗治疗前和治疗后第 1、3 和 7 天测量凝血参数。所有患者在入院后 35 天或直至死亡进行随访。
共纳入 70 例患者（平均年龄 60 岁，四分位距 52-75）。托珠单抗治疗与 D-二聚体水平降低（-56%；95%置信区间 [CI]，-68%至-44%）、纤维蛋白原降低（-48%；95%CI，-60%至-35%）、C 反应蛋白降低（-93%；95%CI，-99%至-87%）、凝血酶原时间缩短（-4%；95%CI，-9%至 0.8%）和活化部分凝血活酶时间缩短（-4%；95%CI，-8.7%至 0.8%）有关，血小板计数增加（34%；95%CI，23%至 45%）。这些变化在治疗后第一天即出现，并在第 7 天持续减少。在接受预防性或治疗性剂量抗凝治疗的患者中，凝血改善情况一致，且与呼吸功能的迅速改善相平行。
皮下注射托珠单抗可显著改善凝血参数，与抗栓治疗剂量无关。
