VTE Risk Substantially Lower in Breakthrough COVID Cases

While mild COVID-19 increases venous thromboembolism (VTE) risk, those events are much less likely for vaccinated than unvaccinated patients, a large population-based study showed.

COVID-19 overall raised 30-day risk of deep vein thrombosis or pulmonary embolism, with incidence of 50.99 per 1,000 person-years in infected outpatients seen from March 2020 to September 2021, compared with 2.37 cases per 1,000 person-years in uninfected individuals.

But the unvaccinated or partially vaccinated had a 27.94-fold higher risk than uninfected individuals, while fully vaccinated people had only a 5.95-fold higher risk with infection (P=0.02 for interaction), reported Dani Prieto-Alhambra, MD, PhD, of the University of Oxford, England, and colleagues in JAMA Internal Medicine.

“Previous studies had shown that risk of VTE was higher among more severe cases of COVID, and we know that vaccines reduce the severity,” Alhambra told MedPage Today in email correspondence. “We hypothesized this would be the case. So we saw what we expected.”

Other factors independently associated with higher risk in infected patients included male sex and obesity.

Also, COVID-19 patients who had genetically inherited, V Leiden thrombophilia had a 2.07-fold higher risk (95% CI 1.15-3.66) for VTE within 30 days after infection, while each decade of life carried a hazard ratio of 1.87 (95% CI 1.50-2.33).

Genetic testing for VTE has been discussed in other clinical scenarios, so the researchers posited, why not in high risk COVID-19 patients? “This newly identified association with COVID-19–related VTE, comparable with a 10-year aging risk, supports the potential value of targeted genetic screening for thrombophilia in the infected older adults,” the group wrote.

Prieto-Alhambra added that the findings also might suggest preventive measures for high-risk infected individuals and stratifying for VTE risk. “Prophylaxis against VTE (e.g., with anticoagulants) is a recognised strategy for people with severe COVID,” Prieto-Alhambra noted.

However, the paper pointed to “mixed evidence of benefit from anticoagulation” in ambulatory COVID-19 and suggested “prophylaxis, including timing and dosing regimens, requires further refinement.”

Routine use of the anticoagulant enoxaparin to prevent thromboembolic complications provided no benefit for symptomatic outpatients with COVID-19 in the OVID and ETHIC trials; and neither antiplatelet aspirin nor anticoagulant apixaban (Eliquis) helped prevent poor outcomes in clinically stable symptomatic outpatients in the ACTIV-4B platform trial.

The retrospective cohort study relied on data from U.K. Biobank, and included 18,818 infected COVID-19 outpatients who were propensity score-matched in a 1:5 ratio with 93,179 uninfected participants (56.0% women, mean 64 years). In the matched set, 40% were fully vaccinated against SARS-CoV-2 during the study period, while the remainder were not vaccinated or only partially vaccinated.

For those who had a COVID-19 infection, there were 67 cases of VTE in the unvaccinated or partially vaccinated subset (74.96 per 1,000 person-years) versus six cases among the fully vaccinated subset (11.15 per 1,000 patient-years).

Overall, the researchers concluded that the study reinforces the need for vaccination, given this apparent VTE advantage even in breakthrough infections. “This evident benefit should not be ignored in the ongoing global vaccination campaigns.”