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[JAMA发表论文]:纽约市新冠病毒感染住院患者的血栓形成
2020年09月12日 时讯速递, 进展交流 暂无评论

Research Letter July 20, 2020

Thrombosis in Hospitalized Patients With COVID-19 in a New York City Health System

Seda Bilaloglu, Yin Aphinyanaphongs, Simon Jones, et al

JAMA. 2020;324(8):799-801. doi:10.1001/jama.2020.13372

Patients with coronavirus disease 2019 (COVID-19) are at increased risk of thrombosis.1 However, studies have been limited in size, did not report all thrombotic events, and focused on patients with severe disease hospitalized in intensive care units (ICUs). We assessed the incidence of, and risk factors for, venous and arterial thrombotic events in all hospitalized patients with COVID-19 at a large health system consisting of 4 hospitals in New York City.

Methods

This study included consecutive patients aged at least 18 years, admitted to a hospital affiliated with NYU Langone Health between March 1 and April 17, 2020, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using reverse transcriptase–polymerase chain reaction of patient sputum or nasopharyngeal or oropharyngeal swabs. This study was approved by the NYU Grossman School of Medicine Institutional Review Board, which waived the need for informed consent.

Screening for thrombotic events is not standard; diagnoses were made during routine clinical care. Thrombotic events included both venous (deep vein thrombosis [DVT] and pulmonary embolism [PE]) and arterial (myocardial infarction [MI], ischemic stroke, and other systemic thromboembolism). Low-dose (prophylaxis) anticoagulation was used in most patients. As described previously,2 an open-source natural-language processing tool called simpleNLP, with sensitivity and specificity greater than 95%, searched clinical notes and radiology reports for thrombotic events. Additional chart reviews were performed on echocardiograms, presumptive diagnoses, and diagnostic codes for thrombotic end points. All findings were confirmed by manual chart review. Covariate information was obtained from chart review, and mortality was defined as in-hospital death or discharge to hospice as of June 1, 2020.

We investigated risk factors for thrombotic events and conducted competing risk survival analyses. For the end point of mortality, competing risk was discharge; for the end point of thrombosis, competing risks were death or discharge. Variables were included in the models because of their known association with the outcome of interest and statistical differences on multivariable testing, including age, sex, race/ethnicity, body mass index, smoking, comorbidities, and D-dimer levels.

Statistical analyses were conducted using Rstudio (R version 3.5.1). A 2-tailed P< .05 was considered statistically significant.

Results

Among 3334 consecutive hospitalized COVID-19 patients, the median age was 64 (interquartile range, 51-75) years; 39.6% were female. Any thrombotic event (patients could have more than 1) occurred in 533 (16.0%) patients; 207 (6.2%) were venous (3.2% PE and 3.9% DVT) and 365 (11.1%) were arterial (1.6% ischemic stroke, 8.9% MI, and 1.0% systemic thromboembolism; Table 1). Following multivariable adjustment, age, sex, Hispanic ethnicity, coronary artery disease, prior MI, and higher D-dimer levels at hospital presentation were associated with a thrombotic event (Table 2).

共有3334名连续入院的新冠病毒感染患者,中位年龄64 (四分位间距, 51-75) 岁;39.6% 为女性。533 名 (16.0%) 患者发生血栓事件(患者可能发生1个以上血栓事件);207 名 (6.2%) 为静脉血栓 (3.2% PE, 3.9% DVT),365名 (11.1%) 为动脉血栓 (1.6% 缺血性卒中,8.9% 心肌梗塞,1.0% 全身性血栓栓塞;Table 1)。经过多因素校正,年龄,性别,拉美裔,冠心病,既往心肌梗塞以及入院时D-二聚体水平较高与血栓事件相关 (Table 2)。

All-cause mortality was 24.5% and was higher in those with thrombotic events (43.2% vs 21.0%; P < .001) (Table 1). After multivariable adjustment, a thrombotic event was independently associated with mortality (adjusted hazard ratio, 1.82; 95% CI, 1.54-2.15; P < .001). Both venous (adjusted hazard ratio, 1.37; 95% CI, 1.02-1.86; P = .04) and arterial (adjusted hazard ratio, 1.99; 95% CI, 1.65-2.40; P < .001) thrombosis were associated with mortality (P = .25 for interaction).

全因病死率为24.5%,血栓事件患者病死率较高 (43.2% vs 21.0%; P < .001) (Table 1)。多因素校正后,血栓事件与病死率独立相关 (校正HR, 1.82; 95% CI, 1.54-2.15; P < .001)。静脉(校正HR, 1.37; 95% CI, 1.02-1.86; P = .04) 和动脉 (校正HR, 1.99; 95% CI, 1.65-2.40; P < .001) 血栓形成与病死率相关 (交互作用P = .25)。

Among 829 ICU patients, 29.4% had a thrombotic event (13.6% venous and 18.6% arterial). Among 2505 non-ICU patients, 11.5% had a thrombotic event (3.6% venous and 8.4% arterial).

共829名ICU患者中,29.4% 发生血栓事件 (13.6% 静脉,18.6% 动脉)。在2505名非ICU患者中,11.5% 发生血栓事件 (3.6% 静脉,8.4%动脉)。

Discussion

In patients with COVID-19 hospitalized in a large New York City health system, a thrombotic event occurred in 16.0%. D-dimer level at presentation was independently associated with thrombotic events, consistent with an early coagulopathy.

Prior studies varied regarding the precise incidence of thrombosis; however, all suggested a heightened risk in patients with COVID-19.3,4 This analysis found variation by clinical setting and type of thrombosis event. While thrombosis is observed in other acute infections5 (eg, 5.9% prevalence during the 2009 influenza pandemic),6 the thrombotic risk appears higher in COVID-19. Thrombosis in patients with COVID-19 may be due to a cytokine storm, hypoxic injury, endothelial dysfunction, hypercoagulability, and/or increased platelet activity.

This study has several limitations. A diagnosis of thrombosis may be underestimated because imaging studies were limited due to concerns of transmitting infection or competing risk of death. Type of MI was not confirmed with cardiac catheterization. Clinical practice changed over the study period, with increased awareness of thrombotic events and use of anticoagulation, which may affect the incidence of thrombosis.

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