BMJ:新型冠状病毒肺炎后深静脉血栓形成、肺栓塞和出血的风险：全国性自身病例对照系列和配对队列研究

AbstrAct

Objective

To quantify the risk of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19.明确新型冠状病毒肺炎后深静脉血栓形成、肺栓塞和出血的风险。

Design

Self-controlled case series and matched cohort study. 自身病例对照系列和配对队列研究。

Setting

National registries in Sweden. 瑞典国家登记处。

Participants

1 057 174 people who tested positive for SARS- CoV-2 between 1 February 2020 and 25 May 2021 in Sweden, matched on age, sex, and county of residence to 4 076 342 control participants. 2020年2月1日至2021年5月25日，瑞典共1057174人SARS-CoV-2检测阳性，根据年龄、性别和居住地进行匹配，共4076342人纳入对照组。

Main Outcomes Measures

Self-controlled case series and conditional Poisson regression were used to determine the incidence
rate ratio and risk ratio with corresponding 95% confidence intervals for a first deep vein thrombosis, pulmonary embolism, or bleeding event. In the self- controlled case series, the incidence rate ratios for first time outcomes after covid-19 were determined using set time intervals and the spline model. The risk ratios for first time and all events were determined during days 1-30 after covid-19 or index date using the matched cohort study, and adjusting for potential confounders (comorbidities, cancer, surgery, long term anticoagulation treatment, previous venous thromboembolism, or previous bleeding event). 采用自身病例对照和条件泊松回归分析确定首次发生深静脉血栓、肺栓塞或出血事件的发生率比值和风险比，以及相应的95%可信区间。在自身病例对照系列中，采用设定的时间间隔和样条模型确定新型冠状病毒肺炎后首次结局的发生率比值。采用配对队列研究，调整潜在的混杂因素（合并症，肿瘤，手术，长期抗凝治疗，既往有静脉血栓或出血事件）后确定新型冠状病毒肺炎后1～30天或检索日期首次发生所有事件的风险比。

Results

Compared with the control period, incidence rate ratios were significantly increased 70 days after covid-19 for deep vein thrombosis, 110 days for pulmonary embolism, and 60 days for bleeding. In particular, incidence rate ratios for a first pulmonary embolism were 36.17 (95% confidence interval 31.55 to 41.47) during the first week after covid-19 and 46.40 (40.61 to 53.02) during the second week. Incidence rate ratios during days 1-30 after covid-19 were 5.90 (5.12 to 6.80) for deep vein thrombosis, 31.59 (27.99 to 35.63) for pulmonary embolism, and 2.48 (2.30 to 2.68) for bleeding. Similarly, the risk ratios during days 1-30 after covid-19 were 4.98 (4.96 to 5.01) for deep vein thrombosis, 33.05 (32.8 to 33.3) for pulmonary embolism, and 1.88 (1.71 to 2.07) for bleeding, after adjusting for the effect of potential confounders. The rate ratios were highest in patients with critical covid-19 and highest during the first pandemic wave in Sweden compared with the second and third waves. In the same period, the absolute risk among patients with covid-19 was 0.039% (401 events) for deep vein thrombosis, 0.17% (1761 events) for pulmonary embolism, and 0.101% (1002 events) for bleeding. 与对照组相比，新型冠状病毒肺炎后70天发生深静脉血栓、110天发生肺栓塞和60天发生出血的发生率比值均显著增加。特别是，新型冠状病毒肺炎后第1周和第二周首次肺栓塞的发生率比值分别为36.17（95%可信区间31.55~41.47）、46.40（40.61 ~ 53.02）。新型冠状病毒肺炎后1 ~ 30 天内深静脉血栓、肺栓塞和出血的发生率比值分别为5.90（5.12 ~ 6.80）、31.59（27.99 ~ 35.63）、2.48（2.30 ~ 2.68）。同样，调整潜在混杂因素的影响后，新型冠状病毒肺炎后1~ 30天深静脉血栓、肺栓塞和出血的风险比分别为4.98（4.96~ 5.01）、33.05（32.8~ 33.3）、1.88（1.71~ 2.07）。重症新型冠状病毒肺炎患者的风险比最高，且与瑞典的第二波和第三波疫情相比，第一波疫情的风险比最高。同期，新型冠状病毒肺炎患者发生深静脉血栓、肺栓塞和出血事件的绝对风险分别为0.039%（401次事件）、0.17%（1761次事件）、0.101%（1002次事件）。

Conclusions

The findings of this study suggest that covid-19 is a risk factor for deep vein thrombosis, pulmonary embolism, and bleeding. These results could impact recommendations on diagnostic and prophylactic strategies against venous thromboembolism after covid-19. 研究结果表明，新型冠状病毒肺炎是发生深静脉血栓、肺栓塞和出血的危险因素。这些结果可能会影响新型冠状病毒肺炎后静脉血栓栓塞诊断和预防策略的建议。