Adenovirus Vaccines and Blood Clots

December 8, 2021

New research suggests how COVID-19 adenovirus vaccines may lead to extremely rare cases of thrombosis with thrombocytopenia syndrome (TTS), an autoimmune response which can lead to fatal blood clots. Thrombosis with thrombocytopenia was verified by the WHO as a possible adverse event to AstraZeneca and Johnson & Johnson COVID-19 vaccines earlier this year, following the first but rarely after the second dose.

If the adenovirus – the mechanism used to deliver the coronavirus gene into human cells – leaks into the bloodstream, it has the potential to bind to blood proteins responsible for clotting. Current evidence indicates that TTS appears to be driven by specific autoantibodies (anti-PF4) which cluster and create more autoantibodies. “This creates a positive feedback loop as antibodies bind to increasing copies of PF4, stimulating further platelet activation, culminating in the activation of the clotting cascade.” As a response, the body releases antibodies against the protein, with the extremely rare chance of causing blood clots to form. Researchers note that whether anti-PF4 autoantibodies induce thrombosis or not, “is a function of concentration and antibody affinity for PF4.” Recent case reports indicated that over 90% of patients presenting with TTS tested positive for anti-PF4 antibodies.

The study’s investigators found that patients who developed TTS had not been treated with heparin before vaccination. Heparin is an anticoagulant used to prevent blood clots, but it is not recommended that patients take heparin to inhibit the interaction between adenovirus vaccines and PF4 antibodies, nor should patients take heparin following the development of symptoms after vaccination.

Researchers hypothesize that understanding the interaction between adenoviruses and blood proteins may present an opportunity to engineer the outer shell of the vaccine to prevent this from happening. Furthermore, studies are needed to confirm whether adenovirus complexes can induce thrombosis when anti-PF4 antibodies are present.