The first dose of AstraZeneca’s COVID-19 vaccine was associated with a "very small" increased risk of bleeding and other rare blood disorders, researchers say.

Findings published in Nature Medicine on Wednesday stemmed from a study in Scotland, involving 2.53 million people who received first doses of COVID-19 vaccines between Dec. 8 to April 14, comprising 57.5% of the country’s adult population. Of the total, some 1.7 million people received AstraZeneca’s vaccine, and about 820,000 people were administered Pfizer’s vaccine.

While the AstraZeneca COVID-19 vaccine is not yet authorized for use in the U.S., an independent committee advising vaccinations in the U.K. previously recommended those aged 18-39 with no underlying health issues be provided an alternative to the jab given rare cases involving clotting and low platelet count. As of April 21, the U.K. regulatory body (MHRA) received 209 reports of clotting and low platelet levels against a backdrop of 22 million first doses and nearly 7 million second doses of the AstraZeneca vaccine, per the study.

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Researchers reported an increased risk of abnormally low platelet count within six days of vaccination with AstraZeneca’s product. There were 1.33 more events of thrombocytopenia per 100,000 than expected. Researchers also found an incidence of 1.13 cases per 100,000 of so-called idiopathic thrombocytopenic purpura (ITP), or a blood disorder involving an abnormal drop in the number of platelets, per Hopkins Medicine. ITP was "most pronounced" about 21 to 27 days post-vaccination, but was seen seven days post-vaccination. 

"This very small risk is important but needs to be seen within the context of the very clear benefits of the ChAdOx1 vaccine," study authors wrote.

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The issue was found more often among older adults; researchers noted ITP during AstraZeneca's post-vaccination period for 40–49-year-olds 0.62 more events than expected per 100,000 doses, and in the adults under study, there were 0.46 more events than expected per 100,000 doses.

Study authors reported 22 patients with the abnormal drop in platelet count, though nearly half had prior prescriptions that could bring on the issue. The study suggests very few ITP patients were prescribed ITP therapies after receiving AstraZeneca’s vaccine.

Researchers noted three deaths post-ITP, though not due to ITP, and the deaths occurred in both vaccinated and unvaccinated people over age 70.

"First dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events. Given these small increased risks for ChAdOx1, alternative vaccines for individuals at low COVID-19 risk might be warranted when supply allows," study authors wrote.

The heightened risk for so-called arterial thromboembolic events occurred within 27 days after receiving the AstraZeneca vaccine, though fewer cases cropped up than expected (3,288 versus 3,328), and hemorrhagic, or bleeding, events occurred within 27 days of vaccination, though fewer cases were observed than expected (301 vs 349).

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No such issues were found with Pfizer’s vaccine.

Researchers couldn't draw firm conclusions about an association to clotting issues, including the rare but deadly cerebral venous sinus thrombosis, CVST. Six cases of CVST occurred in vaccinated individuals with AstraZeneca’s product, and researchers suspected the outcome is likely "extremely rare."

Study authors suggested public health officials inform people of the "relatively small increased risks associated" with AstraZeneca’s vaccine.