Clark Chantal C, Jukema Bernard N, Barendrecht Arjan D, Spanjaard Judith S, Jorritsma Nikita K N, Smits Simone, de Maat Steven, Seinen Cor W, Verhoef Sandra, Parr Naomi M J, Sebastian Silvie A E, Koekman Arnold C, van Wesel Annet C W, van Goor Harriet M R, Spijkerman Roy, Bongers Suzanne H, van der Vries Erhard, Nierkens Stefan, Boes Marianne, Koenderman Leo, Kaasjager Karin A H, Maas Coen
Department of Central Diagnostic Laboratory Research, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
Front Med (Lausanne). 2021 Apr 22;8:650129. doi: 10.3389/fmed.2021.650129. eCollection 2021.
Coronavirus disease of 2019 (COVID-19) is associated with a prothrombotic state and a high incidence of thrombotic event(s) (TE). To study platelet reactivity in hospitalized COVID-19 patients and determine a possible association with the clinical outcomes thrombosis and all-cause mortality. Seventy nine hospitalized COVID-19 patients were enrolled in this retrospective cohort study and provided blood samples in which platelet reactivity in response to stimulation with ADP and TRAP-6 was determined using flow cytometry. Clinical outcomes included thrombotic events, and all-cause mortality. The incidence of TE in this study was 28% and all-cause mortality 16%. Patients that developed a TE were younger than patients that did not develop a TE [median age of 55 vs. 70 years; adjusted odds ratio (AOR) = 0.96 per 1 year of age, 95% confidence interval (CI) 0.92-1.00; = 0.041]. Furthermore, patients using preexisting thromboprophylaxis were less likely to develop a thrombotic complication than patients that were not (18 vs. 54%; AOR = 0.19, 95% CI 0.04-0.84; = 0.029). Conversely, having asthma strongly increased the risk on TE development (AOR = 6.2, 95% CI 1.15-33.7; = 0.034). No significant differences in baseline P-selectin expression or platelet reactivity were observed between the COVID-19 positive patients ( = 79) and COVID-19 negative hospitalized control patients ( = 21), nor between COVID-19 positive survivors or non-survivors. However, patients showed decreased platelet reactivity in response to TRAP-6 following TE development. We observed an association between the use of preexisting thromboprophylaxis and a decreased risk of TE during COVID-19. This suggests that these therapies are beneficial for coping with COVID-19 associated hypercoagulability. This highlights the importance of patient therapy adherence. We observed lowered platelet reactivity after the development of TE, which might be attributed to platelet desensitization during thromboinflammation.
2019年冠状病毒病（COVID-19）与血栓前状态及血栓事件（TE）的高发生率相关。为研究住院COVID-19患者的血小板反应性，并确定其与血栓形成临床结局及全因死亡率之间可能存在的关联。本回顾性队列研究纳入了79例住院COVID-19患者，并采集了血样，使用流式细胞术测定了血小板对ADP和TRAP-6刺激的反应性。临床结局包括血栓事件和全因死亡率。本研究中TE的发生率为28%，全因死亡率为16%。发生TE的患者比未发生TE的患者更年轻[中位年龄分别为55岁和70岁；调整优势比（AOR）=每增加1岁为0.96，95%置信区间（CI）0.92 - 1.00；P = 0.041]。此外，与未使用预防性抗凝治疗的患者相比，使用过预防性抗凝治疗的患者发生血栓并发症的可能性更小（18%对54%；AOR = 0.19，95%CI 0.04 - 0.84；P = 0.029）。相反，患有哮喘会显著增加发生TE的风险（AOR = 6.2，95%CI 1.15 - 33.7；P = 0.034）。在COVID-19阳性患者（n = 79）和COVID-19阴性住院对照患者（n = 21）之间，以及COVID-19阳性幸存者与非幸存者之间，未观察到基线P-选择素表达或血小板反应性的显著差异。然而，患者在发生TE后对TRAP-6的血小板反应性降低。我们观察到使用预防性抗凝治疗与COVID-19期间TE风险降低之间存在关联。这表明这些治疗方法有助于应对COVID-19相关的高凝状态。这突出了患者坚持治疗的重要性。我们观察到发生TE后血小板反应性降低，这可能归因于血栓炎症期间血小板的脱敏作用。
