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Increased procoagulant platelet levels are predictive of death in COVID-19
GeroScience ( IF 5.3 ) Pub Date : 2021-06-09 , DOI: 10.1007/s11357-021-00385-3
Mohamad H Khattab 1, 2 , Calin I Prodan 2, 3 , Andrea S Vincent 4 , Chao Xu 5 , Kellie R Jones 1, 2 , Sharanjeet Thind 1, 2 , Meheroz Rabadi 2, 3 , Shubhada Mithilesh 2 , Eleanor Mathews 3 , Leslie Guthery 3 , George L Dale 1 , Angelia C Kirkpatrick 1, 2
Affiliation  

Prior research has identified abnormal platelet procoagulant responses in COVID-19. Coated-platelets, a form of procoagulant platelets, support thrombin formation and are elevated in ischemic stroke patients with increased risk for recurrent infarction. Our goal was to examine changes in coated-platelet levels over the course of COVID-19 infection and determine their association with disease severity, thrombosis, and death. Coated-platelet levels were assayed after admission and repeated weekly in COVID-19 patients, and in COVID-19 negative controls. Receiver operator characteristic (ROC) analysis was used to calculate area under the curve (AUC) values for a model including baseline coated-platelets to predict death. Kaplan–Meier and Cox proportional hazards analysis was used to predict risk for death at 90 days. We enrolled 33 patients (22 with moderate and 11 with severe infection) and 20 controls. Baseline coated-platelet levels were lower among moderate (mean ± SD; 21.3 ± 9.8%) and severe COVID-19 patients (28.5 ± 11.9%) compared to controls (38.1 ± 10.4%, p < 0.0001). Coated-platelet levels increased during follow-up in COVID-19 patients by 7% (relative) per day from symptom onset (95% CI 2–12%, p = 0.007). A cut-off of 33.9% for coated-platelet levels yielded 80% sensitivity and 96% specificity for death at 90 days, with resulting AUC of 0.880 (95% CI 0.680–1.0, p = 0.0002). The adjusted hazard ratio for death in patients with coated-platelet levels > 33.9% was 40.99 when compared to those with levels ≤ 33.9% (p < 0.0001). Platelet procoagulant potential is transiently decreased in most patients during COVID-19; however, increased baseline platelet procoagulant levels predict death. Defining the mechanisms involved and potential links with aging may yield novel treatment targets.



中文翻译:

促凝血小板水平升高可预测 COVID-19 的死亡

先前的研究已经确定了 COVID-19 中异常的血小板促凝反应。涂层血小板是促凝血小板的一种形式,支持凝血酶的形成,并且在缺血性中风患者中升高,复发性梗塞的风险增加。我们的目标是检查在 COVID-19 感染过程中涂层血小板水平的变化,并确定它们与疾病严重程度、血栓形成和死亡的关联。在 COVID-19 患者和 COVID-19 阴性对照中,在入院后测定涂层血小板水平并每周重复一次。接受者操作特征 (ROC) 分析用于计算模型的曲线下面积 (AUC) 值,该模型包括用于预测死亡的基线涂层血小板。Kaplan-Meier 和 Cox 比例风险分析用于预测 90 天时的死亡风险。我们招募了 33 名患者(22 名中度感染,11 名重度感染)和 20 名对照。与对照组 (38.1 ± 10.4%, p < 0.0001) 相比,中度(平均值 ± SD;21.3 ± 9.8%)和重度 COVID-19 患者(28.5 ± 11.9%)的基线涂层血小板水平较低。在 COVID-19 患者的随访期间,从症状出现开始,涂层血小板水平每天增加 7%(相对)(95% CI 2–12%,p = 0.007)。90 天时,涂层血小板水平的临界值为 33.9%,对死亡的敏感性为 80%,特异性为 96%,AUC 为 0.880(95% CI 0.680–1.0,p = 0.0002)。与水平≤ 33.9% 的患者相比,涂层血小板水平 > 33.9% 的患者的调整后死亡风险比为 40.99 (p < 0.0001)。在 COVID-19 期间,大多数患者的血小板促凝潜力暂时降低;然而,增加的基线血小板促凝水平预示着死亡。定义所涉及的机制以及与衰老的潜在联系可能会产生新的治疗目标。

更新日期:2021-06-10
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