Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study

Abstract

Objective: To quantify the risk of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19.

Design: Self-controlled case series and matched cohort study.

Setting: National registries in Sweden.

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.

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).

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.

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.

Fig 1

Overview of self-controlled case series study design, including risk periods, periods before exposure to SARS-CoV-2, and control periods. The covid-19 date was set as the earliest from the date of disease onset, sample date, diagnosis date, or date of report to the communicable disease surveillance system SmiNet (Public Health Agency of Sweden)

Fig 2

Adjusted relative risks with 95% confidence intervals of a first deep vein thrombosis, pulmonary embolism, and bleeding event within 30 days after covid-19 in matched cohort study adjusted for weighted Charlson comorbidity index score, cancer, surgery, and long term anticoagulation treatment. Total cohort consists of individuals who tested positive for SARS-CoV-2 and those who were not reported to the Public Health Agency of Sweden (test negative) as baseline

Fig 3

Adjusted relative risks with 95% confidence intervals of a first deep vein thrombosis, pulmonary embolism, and bleeding event within 30 days after covid-19 in matched cohort study adjusted for weighted Charlson comorbidity index score, cancer, surgery, and long term anticoagulation treatment, and stratified according to disease severity using control participants who were not reported to the Public Health Agency of Sweden (test negative) as baseline. ICU=intensive care unit