Association Discovered Between Common Cold Virus and Serious Blood Clotting Disorder

Platelets, also known as thrombocytes, are specialized cellular fragments responsible for the formation of blood clots when our body experiences scrapes or traumatic injuries. Conditions such as viral infections, autoimmune diseases, and others can lead to a decrease in platelet count, a condition referred to as thrombocytopenia. In an extensive collaborative effort between Dr. Stephan Moll and Dr. Jacquelyn Baskin-Miller, both affiliated with the UNC School of Medicine, a connection has been established between adenovirus infections and a rare blood clotting disorder. This remarkable discovery marks the first instance where the widespread respiratory adenovirus, typically associated with mild cold and flu symptoms, has been implicated in severe thrombocytopenia and blood clotting.

Dr. Moll, a professor of medicine in the Division of Hematology at the Department of Medicine, stated, “This adenovirus-associated disorder is now recognized as one of the four anti-PF4 disorders. We hope that our findings will lead to earlier diagnosis, improved treatment strategies, and better outcomes for patients facing this life-threatening condition.” Their groundbreaking observation has been published in the New England Journal of Medicine, shedding new light on the virus’s role in causing an anti-platelet factor 4 disorder. Furthermore, this discovery has opened up new avenues for research, as many questions remain regarding the mechanisms and predisposing factors behind this condition.

Antibodies are large Y-shaped proteins that can adhere to the surfaces of bacteria and other foreign substances, marking them for destruction by the immune system or neutralizing the threat directly. In anti-PF4 disorders, the immune system produces antibodies against platelet factor-4 (PF4), a protein released by platelets. When these antibodies form against PF4 and bind to it, it can trigger the activation and rapid removal of platelets from the bloodstream, resulting in blood clotting and decreased platelet levels. Sometimes, the formation of anti-PF4 antibodies is prompted by a patient’s exposure to heparin, termed heparin-induced thrombocytopenia (HIT). In other cases, it arises as an autoimmune condition without heparin exposure, referred to as “spontaneous HIT.”

In recent years, thrombocytopenia has been observed rarely after the administration of COVID-19 vaccines constructed with inactivated components of an adenoviral vector, distinct from vaccines made in the United States by companies like Moderna and Pfizer. This condition is known as vaccine-induced immune thrombotic thrombocytopenia (VITT).

The journey toward this discovery began with the hospitalization of a 5-year-old boy diagnosed with adenovirus infection, who exhibited an aggressive blood clot in his brain and severe thrombocytopenia. Notably, this patient had not been exposed to heparin or the adenovirus vector COVID-19 vaccine, the typical triggers for HIT and VITT. Dr. Baskin-Miller noted, “The medical team was working tirelessly to determine the best course of action for this young patient. His condition was deteriorating rapidly, and we wondered if it could be related to his adenovirus infection based on vaccine data, although there was no prior literature to suggest such a connection.”

To address this perplexing case, Dr. Moll, an expert in thrombosis, was consulted, and he suspected that the young patient might have “spontaneous HIT.” Subsequent testing confirmed the presence of the HIT platelet-activating antibody.

In the pursuit of further insight, Dr. Moll contacted Dr. Theodore E. Warkentin, a renowned researcher in anti-PF4 disorders at McMaster University in Ontario, Canada, who had been studying these disorders for decades. Surprisingly, Dr. Warkentin was unaware of an association between adenoviral infection and spontaneous HIT.

Around the same time, Dr. Moll received a call from Dr. Alison L. Raybould, a hematologist-oncologist in Richmond, Virginia. She was treating a patient who had experienced multiple blood clots, a stroke, a heart attack, deep-vein thromboses in the limbs, and severe thrombocytopenia. This patient had not been exposed to heparin or vaccines but had initially presented with viral symptoms, including cough and fever, and tested positive for adenoviral infection. Testing for an anti-PF4 antibody also yielded positive results.

To clarify the diagnoses of these two patients, Dr. Warkentin offered to conduct further testing on their blood samples in his laboratory. The results confirmed that the antibodies were targeting platelet factor 4, resembling HIT antibodies. Consequently, both patients were diagnosed with “spontaneous HIT” or a VITT-like disorder associated with adenovirus infection.

This groundbreaking discovery has raised several important questions for Dr. Moll and his colleagues. They are eager to determine the prevalence of this new anti-PF4 disorder, investigate whether it can be triggered by other viruses, and understand why it doesn’t occur with every adenovirus infection. Additionally, they are exploring preventive measures and treatment options to improve the survival chances of patients with this potentially deadly condition.

Dr. Moll emphasized, “How common is the disorder? What degree of thrombocytopenia warrants testing for anti-PF4 antibodies? And finally, how can we best treat these patients to increase their chances of survival against this potentially life-threatening disease?”

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