Department of Internal Medicine, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Department of Internal Medicine, Hospital Universitario de Fuenlabrada, Madrid, Spain.
J Thromb Haemost. 2021 Aug;19(8):1981-1989. doi: 10.1111/jth.15400. Epub 2021 Jun 20.
Some local protocols suggest using intermediate or therapeutic doses of anticoagulants for thromboprophylaxis in hospitalized patients with coronavirus disease 2019 (COVID-19). However, the incidence of bleeding, predictors of major bleeding, or the association between bleeding and mortality remain largely unknown.
We performed a cohort study of patients hospitalized for COVID-19 that received intermediate or therapeutic doses of anticoagulants from March 25 to July 22, 2020, to identify those at increased risk for major bleeding. We used bivariate and multivariable logistic regression to explore the risk factors associated with major bleeding.
During the study period, 1965 patients were enrolled. Of them, 1347 (69%) received intermediate- and 618 (31%) therapeutic-dose anticoagulation, with a median duration of 12 days in both groups. During the hospital stay, 112 patients (5.7%) developed major bleeding and 132 (6.7%) had non-major bleeding. The 30-day all-cause mortality rate for major bleeding was 45% (95% confidence interval [CI]: 36%-54%) and for non-major bleeding 32% (95% CI: 24%-40%). Multivariable analysis showed increased risk for in-hospital major bleeding associated with D-dimer levels >10 times the upper normal range (hazard ratio [HR], 2.23; 95% CI, 1.38-3.59), ferritin levels >500 ng/ml (HR, 2.01; 95% CI, 1.02-3.95), critical illness (HR, 1.91; 95% CI, 1.14-3.18), and therapeutic-intensity anticoagulation (HR, 1.43; 95% CI, 1.01-1.97).
Among patients hospitalized with COVID-19 receiving intermediate- or therapeutic-intensity anticoagulation, a major bleeding event occurred in 5.7%. Use of therapeutic-intensity anticoagulation, critical illness, and elevated D-dimer or ferritin levels at admission were associated with increased risk for major bleeding.
一些地方方案建议对患有 2019 年冠状病毒病（COVID-19）的住院患者进行血栓预防时使用中等或治疗剂量的抗凝剂。然而，出血的发生率、大出血的预测因素或出血与死亡率之间的关系在很大程度上仍不清楚。
我们对 2020 年 3 月 25 日至 7 月 22 日期间因 COVID-19 住院并接受中等或治疗剂量抗凝剂的患者进行了队列研究，以确定大出血风险增加的患者。我们使用双变量和多变量逻辑回归来探讨与大出血相关的危险因素。
在研究期间，共纳入 1965 例患者。其中，1347 例（69%）接受中等剂量抗凝治疗，618 例（31%）接受治疗剂量抗凝治疗，两组的中位治疗时间均为 12 天。住院期间，112 例（5.7%）患者发生大出血，132 例（6.7%）患者发生非大出血。大出血的 30 天全因死亡率为 45%（95%置信区间[CI]：36%-54%），非大出血的 30 天全因死亡率为 32%（95% CI：24%-40%）。多变量分析显示，与住院期间大出血相关的风险因素包括 D-二聚体水平>10 倍正常上限（危险比[HR]，2.23；95% CI，1.38-3.59）、铁蛋白水平>500ng/ml（HR，2.01；95% CI，1.02-3.95）、危重症（HR，1.91；95% CI，1.14-3.18）和治疗强度抗凝（HR，1.43；95% CI，1.01-1.97）。
在 COVID-19 住院患者中接受中等或治疗强度抗凝治疗的患者中，大出血发生率为 5.7%。使用治疗强度抗凝、危重症以及入院时 D-二聚体或铁蛋白水平升高与大出血风险增加相关。
