04 May 2022

Some patients who have had COVID-19 have an increased risk of deep vein thrombosis up to three months after infection, pulmonary embolism up to six months, and a bleeding event up to two months, according to a new study.

A Swedish study, published in the latest edition of The BMJ, also shows an increased risk in patients with underlying conditions, those who had more severe COVID-19 and those who tested positive for the virus during the first pandemic wave compared with the second and third waves.

Ioannis Katsoularis, of Umeå University in Sweden, and colleagues say their findings support measures to prevent blood clots through thromboprophylaxis, especially for high-risk patients, and strengthen the importance of vaccination against COVID-19.

It is known that COVID-19 increases the risk of venous thromboembolism (VTE). However, little is known about the length of time this risk is increased, if risk changed during the pandemic waves, and if the virus increases the risk of major bleeding.

The researchers used national registries in Sweden to measure the risk of deep vein thrombosis, pulmonary embolism, and bleeding after COVID-19. They studied more than one million people with confirmed SARS-CoV-2 infection between 1 February 2020 and 25 May 2021.

These were matched by age, sex, and county of residence to more than four million people who had not had a positive SARS-CoV-2 test result.

The team undertook two analyses: they calculated the rates of deep vein thrombosis, pulmonary embolism, and bleeding in COVID-19 individuals during a control period (before and long after COVID-19 diagnosis) and compared it to the rates in different time intervals after COVID-19 diagnosis – days 1-7, 8-14, 15-30, 31-60, 61-90, and 91-180.

A second analysis involved calculating the rates of deep vein thrombosis, pulmonary embolism, and bleeding during the period 1-30 days after COVID-19 diagnosis in the COVID-19 group and comparing to the corresponding rates in the non-infected control group.

They found risks were still significantly increased an estimated 70 days after COVID-19 for deep vein thrombosis, 110 days for pulmonary embolism, and 60 days for bleeding.

After taking into account a range of potential confounding factors, the researchers found a five-fold increase in risk of deep vein thrombosis, a 33-fold increase in risk of pulmonary embolism, and an almost two-fold increase in risk of bleeding in the 30 days after infection.

In absolute terms, this means that a first deep vein thrombosis occurred in 401 patients with COVID-19 (absolute risk 0.04%) and 267 control patients (absolute risk 0.01%).

A first pulmonary embolism event occurred in 1,761 patients with COVID-19 (absolute risk 0.17%) and 171 control patients (absolute risk 0.004%). A first bleeding event occurred in 1,002 patients with COVID-19 (absolute risk 0.10%) and 1,292 control patients (absolute risk 0.04%).

Risks were highest in patients with more severe COVID-19 and during the first pandemic wave compared with the second and third waves. The research team say this could be because of improvements in treatment and vaccine coverage in older patients after the first wave.

The increased risk of deep vein thrombosis and pulmonary embolism was found even among mild, non-hospitalised COVID-19 patients, but no increased risk of bleeding was found in mild cases.

Although this is an observational study and the researchers acknowledge several limitations that might have affected their findings, they add their results were largely consistent with similar studies on the association between COVID-19 and thromboembolic events.

COVID-19 could be an independent risk factor for deep vein thrombosis, pulmonary embolism, and bleeding, they warn, adding: “Our findings arguably support thromboprophylaxis to avoid thrombotic events, especially for high-risk patients, and strengthen the importance of vaccination against COVID-19.”

Source: Katsoularis I, Fonseca-Rodríguez O, Farrington P, Jerndal H, Lundevaller EH, Sund M, Lindmark K, Fors Connolly AM. (2022) “Risks of deep vein thrombosis, pulmonary embolism, and bleeding after COVID-19: nationwide self-controlled cases series and matched cohort study.” BMJ, doi: 10.1136/bmj-2021-069590

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

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