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Factors Linked With Increased VTE Risk in COVID Outpatients

Overall risk for venous thromboembolism (VTE) in nonhospitalized COVID-19 patients is low, but some of those patients may have factors that increase the risk and warrant more surveillance, according to a new retrospective cohort study.

Though VTE risk is well studied and significant in those hospitalized with COVID, little is known about the risk in the outpatient setting, said the authors of the new research published online in JAMA Network Open.

The study was conducted at two integrated health care delivery systems in northern and southern California. Data were gathered from the Kaiser Permanente Virtual Data Warehouse and electronic health records.

Nearly 400,000 patients studied

Researchers, led by Margaret Fang, MD, with the division of hospital medicine, University of California, San Francisco, identified 398,530 outpatients with COVID-19 from Jan. 1, 2020, through Jan. 31, 2021.

VTE risk was low overall for ambulatory COVID patients.

“It is a reassuring study,” Dr. Fang said in an interview.

The researchers found that the risk is highest in the first 30 days after COVID-19 diagnosis (unadjusted rate, 0.58; 95% confidence interval, 0.51-0.67 per 100 person-years vs. 0.09; 95% CI, 0.08-0.11 per 100 person-years after 30 days).

Factors linked with high VTE risk

They also found that several factors were linked with a higher risk of blood clots in the study population, including being at least 55 years old; being male; having a history of blood clots or thrombophilia; and a body mass index (BMI) of at least 30 kg/m2.

The authors write, “These findings may help identify subsets of patients with COVID-19 who could benefit from VTE preventive strategies and more intensive short-term surveillance.”

Are routine anticoagulants justified?

Previously, randomized clinical trials have found that hospitalized patients with moderate COVID-19 may benefit from therapeutically dosed heparin anticoagulants but that therapeutic anticoagulation had no net benefit – and perhaps could even harm – patients who were critically ill with COVID.

“[M]uch less is known about the optimal thromboprophylaxis strategy for people with milder presentations of COVID-19 who do not require hospitalization,” they write.

Mild COVID VTE risk similar to general population

The authors note that rates of blood clots linked with COVID-19 are not much higher than the average blood clot rate in the general population, which is about 0.1-0.2 per 100 person-years.

Therefore, the results don’t justify routine administration of anticoagulation given the costs, inconvenience, and bleeding risks, they acknowledge.

Dr. Fang told this publication that it’s hard to know what to tell patients, given the overall low VTE risk. She said their study wasn’t designed to advise when to give prophylaxis.

Physicians should inform patients of their higher risk

“We should tell our patients who fall into these risk categories that blood clot is a concern after the development of COVID, especially in those first 30 days. And some people might benefit from increased surveillance,” Dr. Fang said.

“I think this study would support ongoing studies that look at whether selected patients benefit from VTE prophylaxis, for example low-dose anticoagulants,” she said.

Dr. Fang said the subgroup factors they found increased risk of blood clots for all patients, not just COVID-19 patients. It’s not clear why factors such as being male may increase blood clot risk, though that is consistent with previous literature, but higher risk with higher BMI might be related to a combination of inflammation or decreased mobility, she said.

Unanswered questions

Robert H. Hopkins Jr., MD, says the study helps answer a couple of important questions – that the VTE risk in nonhospitalized COVID-19 patients is low and when and for which patients risk may be highest.

However, there are several unanswered questions that argue against routine initiation of anticoagulants, notes the professor of internal medicine and pediatrics chief, division of general internal medicine, at University of Arkansas for Medical Sciences, Little Rock.

One is the change in the COVID variant landscape.

“We do not know whether rates of VTE are same or lower or higher with current circulating variants,” Dr. Hopkins said.

The authors acknowledge this as a limitation. Study data predate Omicron and subvariants, which appear to lower clinical severity, so it’s unclear whether VTE risk is different in this Omicron era.

Dr. Hopkins added another unknown: “We do not know whether vaccination affects rates of VTE in ambulatory breakthrough infection.”

Dr. Hopkins and the authors also note the lack of a control group in the study, to better compare risk.

Coauthor Dr. Prasad reports consultant fees from EpiExcellence LLC outside the submitted work. Coauthor Dr. Go reports grants paid to the division of research, Kaiser Permanente Northern California, from CSL Behring, Novartis, Bristol Meyers Squibb/Pfizer Alliance, and Janssen outside the submitted work.

The research was funded through Patient-Centered Outcomes Research Institute.

Dr. Hopkins reports no relevant financial relationships.

This article originally appeared on, part of the Medscape Professional Network.

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