Scientists have identified a new underlying mechanism of platelet activation in vaccine-induced immune thrombocytopenia and thrombosis.

New research may explain why some individuals experience a rare and often fatal blood clotting disorder after receiving a COVID-19 vaccine. In a recent study published Oct. 26 in the peer-reviewed journal Blood, funded by the National Institute for Health and Care Research and the British Heart Foundation, scientists from the University of Birmingham, United Kingdom identified a new mechanism of platelet activation in vaccine-induced immune thrombocytopenia and thrombosis (VITT).

VITT is a clinical syndrome associated with COVID-19 vaccines that is characterized by thrombosis, or blood clots, at uncommon sites and mild to severe thrombocytopenia. Thrombocytopenia occurs when blood platelets are too low, resulting in excessive bleeding. VITT is similar to heparin-induced thrombocytopenia (HIT) but without prior exposure to the popular anticoagulant drug.

“Although VITT only emerged recently, the research that it has triggered is teaching us a lot about how the body works and how it can go wrong,” Richard Buka, co-lead author, and clinical research fellow at the University of Birmingham Institute of Cardiovascular Sciences, told The Epoch Times in an email.

“Our ability to work on VITT has allowed us to discover a new biological pathway—one that was unknown before. This might have relevance to lots of other fields of research, including clotting disorders more generally, and in understanding how the bone marrow makes platelets,” he added.

According to the study, people with VITT or HIT produce antibodies against a small chemokine protein released by activated platelets and form immune complexes—large clusters of molecules that activate platelets and cells of the immune system that cause clotting and inflammation.

“VITT is caused by a misguided immune response which is normally thought to protect us from infection. That immune response leads to strong antibodies against a molecule called platelet factor 4 (PF4),” Mr. Buka told The Epoch Times. “Antibodies and PF4 form large complexes which can then activate platelets and white blood cells, leading to inflammation and blood clots.”

Although scientists knew PF4 played a significant role in promoting blood coagulation and is involved in innate and adaptive immunity when platelets are activated in response to infections, the exact nature of how PF4 contributes to this process was previously unknown.

In the study, researchers collected blood samples from healthy volunteers after vaccination with AstraZeneca’s COVID-19 vaccine and nonvaccinated healthy donors to determine the role PF4 plays in activating platelets leading to thrombotic events.

Researchers found that PF4 binds to a receptor called c-Mpl on the surface of platelets, triggering small cells known to cause clotting. High concentrations of PF4 were shown to induce “robust platelet aggregation” through the c-Mpl thrombopoietin (TPO) receptor, and lower concentrations can increase the likelihood of platelet activation through the same pathway.

The TPO receptor is the chief regulator of megakaryocytes, which are responsible for producing blood platelets. Mr. Buka said he and the authors of the paper have been working on how platelets become activated in VITT.

“Previously, it was thought that the antibodies themselves activate platelets, but we have found a role for PF4 in this process. We discovered that PF4 can bind to a receptor on platelets and increase their activation—making clots more likely to form,” he said.

Knowing the role PF4 plays in VITT may open the door to better treatments for the condition, Mr. Buka added.

“We can block this process with a commonly used drug, ruxolitinib. It’s reasonable to think that this might be a good treatment for VITT, but we think that this is playing a more minor role in platelet activation. However, there are other drugs that we could use to reduce platelet activation, which in theory would be an ideal treatment,” Mr. Buka said.

The limitations of this study include its small sample size and the differing treatments received before participant samples were collected. Additionally, only a limited number of conditions were tested due to the limited sera available, and aggregation was measured only over 10 minutes instead of 30 minutes for those with VITT.

“I’d really like to pay tribute to the patients and their families with VITT who have, and continue to suffer,” Mr. Buka said. “We are privileged to work on these extremely rare blood samples, and we will continue to strive to understand as much as we possibly can about VITT.”

Blood Clotting Disorders Linked to AstraZeneca

European regulators in April 2021 first acknowledged a possible link between AstraZeneca’s COVID-19 vaccine and “very rare” blood clots after a review of 62 cases of cerebral venous sinus thrombosis (CVST) and 24 cases of splanchnic vein thrombosis were reported to the EU drug safety database EudraVigilance during the first few months of Europe’s vaccine rollout.