Oxford–AstraZeneca COVID-19 Vaccine Associated with Small Excess Risk of Deep Venous Thrombosis

Anders Hviid, PhD

A new Danish exploratory retrospective cohort study among frontline workers in Denmark found that receipt of the AZD1222 (Oxford–AstraZeneca) COVID-19 vaccine was associated with a small excess risk for deep venous thrombosis.

Investigators noted that clinically relevant risks could not be excluded with certainty despite not seeing a statistically significant increase in corresponding risks for more rare and severe thrombotic outcomes.

However, there was no statistically significant association of BNT162b2 (Pfizer-BioNTech) vaccination with thrombotic or thrombocytopenic events.

Investigators led by Anders Hviid, PhD, Department of Epidemiology Research at Statens Serum Institute, noted that back in March 2021, several European countries suspended the used of the AZD1222 COVID-19 vaccine out of concern of thromboembolic safety concerns.

With their study, Hviid and colleagues evaluated the risk of outcomes related to thrombosis and thrombocytopenia after vaccination with either theAZD1222 or BNT162b2 COVID-19 vaccine.

The Methods

The team constructed a nationwide cohort of all people born between 1957 and 2005 who were designated as frontline personnel and eligible for priority vaccination by the Danish authorities.

The Danish Civil Registration System was used to link information from national health care registers to the study cohort via a personal identifier.

The identifier linked information on COVID-19 vaccination status, COVID-19 test status, occupation, comorbid conditions, prescription drug use, region, and hospital contacts for relevant thromboembolic outcomes.

From there, data on dates of COVID-19 vaccination in the study cohort was obtained via the Danish vaccination register. As of April 14, 2021, the 2 messenger RNA vaccines, BNT162b2 and mRNA-1273 (Moderna), and the non-replicating viral vector vaccine AZD1222 had been in use in Denmark.

Investigators acquired additional data on the diagnoses of thromboembolic and thrombocytopenic events among study participants from the Danish National Patient Register.

Study outcomes were cerebral venous sinus thrombosis, splanchnic vein thrombosis, pulmonary embolism, deep venous thrombosis, arterial thrombosis, and thrombocytopenia and death.

The Findings

Hviid and colleagues identified 383,728 people born between 1957 and 2005, living in Denmark on December 27, 2020, and designated as frontline personnel by the Danish health authorities. However, they excluded 10,585 who were using antithrombotic drugs at baseline and 17,934 with a positive result on a SARS-CoV-2 test before study start, yielding a cohort comprising 355,209 participants.

A total of 121,152 participants (34.1%) received a first dose of the AZD1222 vaccine, 101,212 (28.5%) received a first dose of the BNT162b2 vaccine, 2205 (0.6%) received a first dose of the mRNA-1273 vaccine, and only 504 (<1% of those vaccinated with AZD1222) received a second dose of AZD1222 vaccine.

Investigators observed that vaccination with AZD1222 compared to no vaccination was associated with a significant risk differences at day 28 of the study for deep venous thrombosis (RD, 8.35 [95% CI, 0.21 to 16.49] per 100 000 vaccinations).

Meanwhile, the RDs for cerebral venous sinus thrombosis (RD, 1.68 [CI, −0.64 to 4.00] per 100 000 vaccinations) and thrombocytopenia (RD, 2.39 [CI, −1.09 to 5.87] per 100 000 vaccinations) were deemed not significant, and no adverse associations were seen for BNT162b2 vaccination.

“Although the corresponding risks for the more rare and severe thrombotic outcomes (such as cerebral venous sinus thrombosis) were not statistically significantly increased, statistical precision was low, and clinically relevant risks could not be excluded with certainty,” the team wrote.