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Overall risk for venous thromboembolism (VTE) was low for typical COVID outpatients, though higher rates were identified in certain groups, suggesting opportunity for targeted interventions or increased short-term surveillance, according to authors of a cohort study.

In the California study of nearly 400,000 outpatients with a confirmed case of COVID-19, VTE was identified in 0.1% (0.26 per 100 person-years, 95% CI 0.24-0.30), a rate not much higher than in the general population (0.1-0.2 per 100 person-years), reported researchers led by Margaret C. Fang, MD, MPH, of the University of California San Francisco.

The bulk of the risk in the cohort -- which included outpatients diagnosed early in the pandemic (January 2020 to January 2021) -- showed up in the first 30 days following a diagnosis (0.58 per 100 person-years, 95% CI 0.51-0.67), the group detailed in .

"Although the absolute risk of VTE was low overall, selected patient characteristics were associated with higher rates of VTE, particularly in the first 30 days after COVID-19 diagnosis," Fang and co-authors wrote. "We identified several subgroups of patients with VTE rates that reached or exceeded the threshold of 4 per 100 person-years, which is when more intensive VTE prevention should be considered."

These included people with a prior VTE (12.44 per 100 person-years in the first 30 days), those with primary or secondary thrombophilia (4.16 per 100 person-years), and people age 75-84 years (3.96 per 100 person-years).

"Current American Society of Hematology guidelines do not recommend the routine use of anticoagulants in outpatients with COVID-19 or in those who have been recently hospitalized," the authors noted.

While prior trials of anticoagulation have shown benefit in certain patients hospitalized for COVID-19, studies in outpatients have shown no benefit.

"Although the low rates of VTE reported in our study do not support the universal use of antithrombotic agents in nonhospitalized patients with COVID-19, our results support the importance of clinical trials that are evaluating whether some higher-risk subgroups may benefit," according to Fang and colleagues.

The current study was conducted before the widespread availability of vaccines, a noted limitation. Previous research has shown that unvaccinated or partially vaccinated outpatients with COVID-19 have a 28-fold higher VTE risk compared with uninfected individuals, while the increased risk was far lower for vaccinated individuals (a 6-fold higher risk vs the uninfected).

For their retrospective study, Fang's group identified 398,530 non-hospitalized patients with a COVID-19 diagnosis from Jan. 1, 2020 to Jan. 31, 2021, with follow-up through Feb. 28, 2021. All individuals were enrolled in Kaiser Permanente Northern California or Kaiser Permanente Southern California.

Mean patient age was 44 years, and 54% were women. Three-fourths of the cohort were white, 11% Asian or Pacific Islander, and 6% were Black. More than half (54%) self-reported Hispanic ethnicity. Risk factors for VTE included a prior VTE in 0.3% of the cohort, thrombophilia in 0.2%, and inflammatory bowel disease (IBD) in 0.5%.

Of the 292 VTE events reported, 57.5% were pulmonary emboli, 34.9% were lower extremity deep venous thromboses (DVT), 5.1% were upper extremity DVTs, and 2.5% were other VTEs at unusual sites.

Multivariable analyses showed higher risk for VTE in people with prior clots (adjusted hazard ratio [aHR] 7.49, 95% CI 4.29-13.07), thrombophilia (aHR 2.52, 95% CI 1.04-6.14), IBD (aHR 2.43, 95% CI 1.02-5.80), dyslipidemia (aHR 1.41, 95% CI 1.02-1.95), along with men (aHR 1.49, 95% CI 1.15-1.96), those with a body mass index (BMI) of 30-39.9 (aHR 1.57, 95% CI 1.06-2.34), a BMI of 40 and up (aHR 3.07, 95% CI 1.95-4.83), and those age 55 and older:

• Age 55-64: aHR 1.85 (95% CI 1.26-2.72)
• Age 65-74: aHR 3.43 (95% CI 2.18-5.39)
• Age 75-84: aHR 5.46 (95% CI 3.20-9.34)
• Age ≥85: aHR 6.51 (95% CI 3.05-13.86)

Due to the time frame, the study was limited to pre-Omicron variants, and therefore may not be generalizable to current variants.

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