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

Mary Wilson

Well-known member
Published 06 April 2022

BMJ 2022; 377 doi: https://doi.org/10.1136/bmj-2021-069590

Ioannis Katsoularis 1, Osvaldo Fonseca-Rodríguez 2, Paddy Farrington 3, Hanna Jerndal 2, Erling Häggström Lundevaller 4, Malin Sund 5 6, Krister Lindmark 1, Anne-Marie Fors Connolly

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.

https://www.bmj.com/content/377/bmj-2021-069590
 
Linked article:

The self-controlled case series method and covid-19

Published 06 April 2022

BMJ 2022; 377 doi: https://doi.org/10.1136/bmj.o625

Paddy Farrington

The self-controlled case series method is one of two approaches used to estimate the association between covid-19 and venous thromboembolism or bleeding. This article briefly describes the method, its assumptions, and how it was implemented in the linked study, and offers some pointers to guide the interpretation of the results.

The self-controlled case series method

The self-controlled case series method is an epidemiological design for estimating the association between an exposure and a health outcome.12 In the linked study (doi:10.1136/bmj-2021-069590), the exposure is covid-19 and the outcome is deep vein thrombosis, pulmonary embolism, or bleeding.3

Key features

The self-controlled case series method automatically adjusts for all multiplicative confounders that do not vary over the duration of the study—automatically meaning that such confounders need not be adjusted for explicitly measured, or even known. This is because estimation is within individuals: individuals act as their own control (hence the term self-controlled). Time varying confounders (such as time, age, or other exposures), however, must be adjusted for explicitly. Also, cases (people who have experienced the outcome) only need be sampled as they contribute to the estimation (hence the term case series).

For these reasons, the method is well suited to the analysis of uncommon outcomes, using data from pre-existing databases with possibly incomplete information on potential confounders. ...

https://www.bmj.com/content/377/bmj.o625
 
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