AstraZeneca COVID-19 Vaccine Linked to Rare Thrombosis, Thrombocytopenia Events

April 9, 2021
Kevin Kunzmann

Kevin Kunzmann is the managing editor for Contagion, as well as its sister publication HCPLive. Prior to joining parent company MJH Life Sciences in 2017, he worked as a health care and government reporter for The Pocono Record, and as a freelance writer for NJ Advance Media, The Express-Times, The Daily Journal, and more. He graduated from Rowan University with a degree in journalism in 2015. In his spare time, he enjoys reading, cooking, running his dog, and complaining about the Mets. Follow him on Twitter @NotADoctorKevin or email him at [email protected]

The newest research of rare adverse events among patients administered the vaccine highlights that venous or arterial thrombosis can develop in unexpected regions, including the brain or abdomen, 5-20 days after administration.

An assessment of the clinical and laboratory features of 11 European patients to experience thrombosis or thrombocytopenia after vaccination with the AstraZeneca COVID-19 vaccine indicated that the adenovirus prophylaxis can result in rare developments of immune thrombotic thrombocytopenia.

The findings, presented by a team of German investigators in The New England Journal of Medicine, associated the risk with the COVID-19 vaccine’s development of platelet factor 4 (PF4) inhibiting antibodies. Clinically, the antibodies mimic autoimmune heparin-induced thrombocytopenia.

The newest contribution to understanding of rare adverse events among patients administered the two-dose vaccine—which is currently available in 70-plus countries—provides clinicians advisory that venous or arterial thrombosis can develop in unexpected regions, including the brain or abdomen, and can become apparent 5-20 days after a patient has been vaccinated with ChAdOx1 nCov-19.

Investigators suggested the novel entity vaccine-induced immune thrombotic thrombocytopenia event be shortened and refrred to as VITT, establishing its unique presence in AstraZeneca vaccine-provided patients, and contrasted from standard heparin-induced thrombocytopenia.

“If such a reaction is accompanied by thrombocytopenia, it can represent an adverse effect of the preceding Covid-19 vaccination,” investigators wrote. “To date, this reaction has been reported only with the ChAdOx1 nCov-19 vaccine, which has been used in approximately 25% of vaccine recipients in Germany and in 30% of those in Austria.”

Led by Andreas Greinacher, MD, of the University of Greifswald School of Medicine in Germany, investigators sought to interpret data on the pathogenesis of the observed clotting disorder in a handful of patients to have received ChAdOx1 nCov-19.

Their assessment included 11 patients in Germany and Austria. The team used an enzyme-linked immunosorbent assay (ELISA) to detect PF4-heparin antibodies, and a modified PF4-enhaced platelet-activation assay to detect platelet-activating antibodies under multiple reaction conditions.

They included samples from patients with blood samples referred for investigation of thrombotic events linked to vaccines; 28 patients tested positive on a screening PF4-heparin immunoassay.

Mean patient age among the original 11 was 36 years (range, 22 – 49), with 9 being women. Patients presented with ≥1 thrombotic event 5-16 days after vaccination, while 1 patient presented with fatal intracranial hemorrhage. Thrombotic events included:

  • 9 cerebral venous thromboses
  • 3 splanchnic-vein thromboses
  • 3 pulmonary embolisms
  • 4 other thromboses
  • 5 disseminated intravascular coagulations
  • 6 deaths

Investigators observed that none of the patients had received heparin prior to symptom onset. All 28 patients who had been positive for PF4-heparin antibodies also tested positive on the platelet-activation assay in the presence of PF4 independent of heparin.

In discussing the findings, Greinacher and colleagues emphasized the availability and benefit of ELISA in detecting potential post-vaccination thrombocytopenia or thrombosis associated with PF4 antibodies. “A strongly positive ELISA result that is obtained in a patient who has not been recently exposed to heparin would be a striking abnormality,” they stressed.

What’s more, a PF4-dependent ELISA or PF4-enhanced platelet-activation assay could be beneficial in confirming such diagnoses at a time when COVID-19 vaccination has been planned for millions with the AstraZeneca product.

“Although treatment decisions such as administering intravenous immune globulin and starting anticoagulation do not need to await laboratory diagnosis, detection of these unusual platelet-activating antibodies will be highly relevant for case identification and future risk–benefit assessment of this and other vaccines,” they wrote.