December 1, 2023

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Common Cold Virus Found to Be Linked to Life-Threatening Blood Clotting Disorder

Common Cold Virus Found to Be Linked to Life-Threatening Blood Clotting Disorder

Common Cold Virus Found to Be Linked to Life-Threatening Blood Clotting Disorder.

Platelets, also known as blood platelets, are specialized cell fragments that form blood clots when we experience scrapes and injuries.

Virus infections, autoimmune diseases, among other conditions, can lead to a decrease in the number of platelets in the body, a condition known as thrombocytopenia.

Through extensive clinical and research collaboration, Dr. Stephan Moll and Dr. Jacquelyn Baskin-Miller of the United Nations University Medical School have discovered a connection between adenovirus infections and a rare clotting disorder.

This finding marks the first association of this widely prevalent respiratory virus with blood clotting and severe thrombocytopenia, despite the virus typically causing mild symptoms similar to the common cold and flu.

Dr. Moll, a Professor of Hematology in the Department of Medicine, stated, “This adenovirus-associated condition is now recognized as one of the four known anti-PF4 disorders. We hope that our research findings will lead to earlier diagnosis, appropriate and optimized treatment, and improved outcomes for patients suffering from this life-threatening disorder.”

Common Cold Virus Found to Be Linked to Life-Threatening Blood Clotting Disorder

Stephen Moore, MD. Source: United Nations University Blood Research Center

Their new observations are published in the New England Journal of Medicine, revealing the role of the virus in causing disruption to anti-platelet factor 4 (PF4). Furthermore, this discovery opens up an entirely new avenue of research, as there remain many questions about how this disease develops, why it occurs, and who is most susceptible.

HIT, VITT, and “Spontaneous HIT”

Antibodies are large Y-shaped proteins that can attach to the surface of bacteria and other “foreign” substances, marking them for destruction by the immune system or neutralizing the threat directly.

In anti-platelet factor 4 disorders, patients’ immune systems produce antibodies against platelet factor 4 (PF4), a protein released by platelets. When antibodies against PF4 form and bind to it, it triggers platelet activation and rapid clearance from the blood, resulting in both blood clotting and low platelet counts.

Sometimes, the formation of anti-PF4 antibodies is triggered by a patient’s exposure to heparin, known as heparin-induced thrombocytopenia (HIT), and sometimes it occurs in the absence of heparin exposure, known as “spontaneous HIT.”

Over the past three years, research has shown rare cases of thrombocytopenia following COVID-19 vaccine administration, particularly those made from inactivated adenovirus vector fragments. These vaccines differ from those produced in the United States, such as those by Moderna and Pfizer. This condition is termed vaccine-induced immune thrombocytopenia (VITT).

The Path to Discovery

The discovery of vaccine-induced immune thrombotic thrombocytopenia (VITT) began when a 5-year-old boy diagnosed with adenovirus infection presented with invasive blood clots in the brain (cerebral venous sinus thrombosis) and severe thrombocytopenia, requiring hospitalization. Doctors confirmed that he had not been exposed to heparin or the adenovirus vector COVID-19 vaccine, which are typical triggers for HIT and VITT.

Baskin-Miller said, “Intensive care physicians, neurointensivists, and the hematology team worked tirelessly day and night to determine the next treatment steps for this young boy. He did not respond to treatment, and his condition progressed rapidly. Given the vaccine data, we suspected a link to his adenovirus, but there were no hints in the literature at the time.”

Collaborative efforts to assist the patients continued to expand: Baskin-Miller reached out to Moll, an expert in thrombosis with various connections in the field. Moll believed that the child may have had “spontaneous HIT.” Subsequently, they tested for HIT platelet-activating antibodies, and the results were positive.

The Key is Collaboration

Moll contacted Dr. Theodore E. Warkentin, a Professor of Pathology and Molecular Medicine at McMaster University in Hamilton, Ontario, to inquire whether there was any connection between adenovirus infection and spontaneous HIT. Warkentin is a leading international researcher on anti-PF4 disorders but was unaware of this scenario.

Around the same time, Moll received a call from Dr. Alison L. Raybould, a hematologist-oncologist in Richmond, Virginia, who had previously trained at the United Nations University. She was treating a patient with multiple blood clots, strokes, heart disease, deep vein thrombosis (DVT) in the arms and legs, and severe thrombocytopenia.

The patient had not been exposed to heparin or vaccines. However, the patient’s severe illness began with viral symptoms like cough and fever, and her adenovirus infection test came back positive. Antibody testing for anti-PF4 also yielded positive results.

To help clarify the diagnoses for these two patients, Warkentin immediately proposed further blood testing and sent samples to his laboratory at Hamilton General Hospital for additional research. They confirmed that the antibodies were targeting platelet factor 4, similar to HIT antibodies.

Surprisingly, these antibodies were similar to VITT antibodies, and the region binding to PF4 was the same as in VITT antibodies. Their conclusion was that both patients had “spontaneous HIT” or a condition similar to VITT, linked to adenovirus infection.

More Questions Remain

After arriving at this groundbreaking conclusion, Moll and his colleagues have many more questions: What is the incidence of these new anti-PF4 disorders? Could other viruses also be responsible for this condition? Why doesn’t this happen every time there’s an adenovirus infection? They also want to know what prevention or treatment measures might help patients with these new, potentially fatal anti-PF4 disorders.

“How common is this condition?” Moll asks. “To what extent should platelet counts decrease before testing for anti-PF4 antibodies? Finally, how can we best treat these patients to improve their chances of survival in this potentially fatal condition?”

Common Cold Virus Found to Be Linked to Life-Threatening Blood Clotting Disorder

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