VTE Related to SARS-CoV-2 Infection Less of a Problem in Outpatients

The findings argue against routine use of VTE prophylaxis outside of a hospital setting, the researchers say.

VTE Related to SARS-CoV-2 Infection Less of a Problem in Outpatients

In contrast to the elevated risk of venous thromboembolism (VTE) observed in patients hospitalized with COVID-19, outpatients with SARS-CoV-2 infection do not appear to carry a greater risk, a study out of the Kaiser Permanente Northern California system shows.

When looking at all VTE events identified in the study, the rate was higher in those with a positive SARS-CoV-2 test versus those without (7.6 vs 5.2 per 1,000 participants; P < 0.001), researchers led by Nareg Roubinian, MD (Kaiser Permanente Northern California Division of Research and the Permanente Medical Group, Oakland, CA), report.

That difference, however, was driven by events that occurred during or after a hospitalization (5.8 vs 3.0 per 1,000 participants; P < 0.001), and not those that occurred in the outpatient setting (1.8 vs 2.2 per 1,000 participants; P = 0.16).

“It was surprising and reassuring to see that the incidence of blood clots in people with COVID-19 who were not hospitalized was similar to what we saw in patients without COVID-19,” Roubinian told TCTMD via email.

He and his colleagues conclude the findings, published online April 5, 2021, in a research letter in JAMA Internal Medicine, “argue against the routine use of outpatient thromboprophylaxis outside of clinical trials.”

They add, “Recognizing that COVID-19-associated symptoms and disability may persist for months, clinical trials and additional longitudinal studies are needed to understand the role of outpatient and hospital treatment in 90-day VTE.”

It became clear in the early stages of the pandemic that patients hospitalized with COVID-19, particularly those who required intensive care, had a greater risk of thromboembolic events. “But most people with COVID-19 do not need to be hospitalized, and we needed to know how often patients outside the hospital were having blood clots,” Roubinian told TCTMD.

To tackle that issue, he and his colleagues examined data on 220,588 symptomatic adults (mean age 47.1; 59.4% women) tested for SARS-CoV-2 in the integrated Kaiser Permanente Northern California system between February 25 and August 31, 2020. Most (86%) were tested in the outpatient setting, with 9% undergoing testing in the emergency department and 5% during hospitalization. Overall, 11.8% of the tests came back positive.

Blood clots do occur in COVID-19 patients but not on a scale where we need to put all or many COVID outpatients on blood thinners. Nareg Roubinian

Within 30 days of testing, VTE was diagnosed in a higher proportion of patients with a positive versus negative test result (0.8% vs 0.5%; P < 0.001). The disparity between testing groups was attributed to a higher rate of hospital-associated, but not outpatient, VTE in those with a positive result. Drilling down further, there was a significantly higher rate of inpatient VTE (4.8 vs 1.8 per 1,000 participants; P < 0.001) but not posthospitalization VTE (1.0 vs 1.1 per 1,000 participants; P = 0.51) among those with SARS-CoV-2 infection.

“Our study examines how often blood clots occur in the time period from infection prior to developing worsened illness that would require hospitalization,” Roubinian explained, saying that it “suggests that blood clots did not occur as frequently during that time period as they did during COVID-19 hospitalizations.”

Asked what this means for the use of prophylactic or therapeutic anticoagulation in patients with SARS-CoV-2 infection, Roubinian said the results indicate “that we need to wait for the results from clinical trials to determine the best treatment approach and not routinely put outpatients on blood thinners. Guidelines continue to recommend blood thinners to prevent blood clots in patients who are hospitalized with COVID-19.”

However, he added, the study suggests it is important to find ways to identify outpatients with SARS-CoV-2 infection that have a high risk of requiring hospitalization in the future. “Some of these patients would be likely to benefit from blood thinners to prevent future blood clots,” he said.

What the analysis cannot address, Roubinian said, is the ongoing discussion about the potential for rare blood clots associated with use of the COVID-19 vaccine from AstraZeneca and the University of Oxford. “Researchers are studying that data now to learn more.”

For now, Roubinian said, “our findings suggest that blood clots do occur in COVID-19 patients but not on a scale where we need to put all or many COVID outpatients on blood thinners. As we have learned with other potential therapies for COVID-19, blood thinners need to be prospectively studied in a clinical trial to determine if they improve patient outcomes.”

In addition, he said, further studies are required to examine the long-term thrombotic risks associated with COVID-19 and to determine whether treatments that stall progression of the disease can also lower risk of blood clots.

Todd Neale is the Associate News Editor for TCTMD and a Senior Medical Journalist. He got his start in journalism at …

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  • The study was funded by The Permanente Medical Group Delivery Science and Applied Research Program.
  • Roubinian reports receiving grants from the National Institutes of Health and the National Heart, Lung, and Blood Institute during the conduct of the study.