Prior to this study, anti-platelet factor 4 disorder was thought to be caused by exposure to heparin or autoimmune conditions.
The adenovirus infection, which causes the common cold, has been linked with a rare blood clotting disorder, according to the results of a case study published in the New England Journal of Medicine.
When an individual gets a viral infection, autoimmune disease, or other conditions, platelet levels—or thrombocytes—can drop throughout the body, which is called thrombocytopenia. For the first time, a robust clinical and research collaboration has linked the common respiratory virus with blood clots and severe thrombocytopenia, according to the study authors.
The observation sheds new light on the virus and its role in causing an anti-platelet factor 4 (anti-PF4) disorder. In addition, the discovery opens new avenues for research, as questions remain as to how and why the condition occurs and who is most likely to develop it.
“This adenovirus-associated disorder is now one of 4 recognized anti-PF4 disorders” said Stephen Moll, MD, professor of medicine in the University of North Carolina (UNC) Department of Medicine’s Division of Hematology, in a press release. “We hope that our findings will lead to earlier diagnosis, appropriate and optimized treatment, and better outcomes in patients who develop this life-threatening disorder.”
In anti-PF4 disorders, an individual’s immune system creates antibodies against PF4, a protein that is released by platelets. However, when an antibody forms against PF4 and binds to it, activation and rapid removal of platelets in the bloodstream can be triggered and lead to blood clotting and low platelets.
Occasionally, a patient’s exposure to heparin, called heparin-induced thrombocytopenia (HIT), triggers the formation of anti-PF4 antibodies. Sometimes, it occurs as an autoimmune condition without any previous heparin exposure, which is called spontaneous HIT.
Researchers began their path toward results once a 5-year-old boy with adenovirus infection was admitted to the hospital with an aggressive blood clot forming in his brain—called cerebral sinus vein thrombosis—and severe thrombocytopenia.
However, the patient was not exposed to heparin, or the adeno-vector COVID-19 vaccination, which has been shown to rarely cause vaccine-induced immune thrombotic thrombocytopenia (VITT) after injection. The boy was not responding to therapy and his disease was progressing quickly, yet physicians could not figure out the reasoning behind the boy’s condition.
Jacquelyn Baskin-Miller, MD, a co-collaborator on the study, reached out to Moll, an expert in thrombosis with various connections in the field. Moll hypothesized that the patient could have spontaneous HIT, and testing for the HIT platelet activating antibody came back positive.
Moll then reached out to Theodore E. Warkentin, MD, who had been researching anti-PF4 disorders for decades, to inquire whether he was aware of a link between adenoviral infection and spontaneous HIT, which he was not.
Around the same period, Moll received a call from Alison L. Raybould, MD, a previous trainee from UNC who was treating a patient with multiple blood clots, stroke, heart attack, arm and leg deep-vein thromboses, and severe thrombocytopenia. The patient was not exposed to any traditional triggers, but did have viral symptoms when his illness began, and tested positive for adenoviral infection. Anti-PF4 antibody testing was also positive.
Warkentin offered to further test the patient’s blood at his laboratory in Hamilton General Hospital, and they confirmed that the antibodies were targeting PF4, much like HIT antibodies. The investigators concluded that each patient had spontaneous HIT associated with an adenovirus infection.
The investigators are now faced with questions regarding this newfound discovery. These questions include determining the prevalence of this new anti-PF4 disorder, whether the condition can be caused by other viruses, and why the condition doesn’t occur with every adenovirus infection, according to the study authors.
“How common is the disorder? What degree of thrombocytopenia raises the threshold to test for anti-PF4 antibodies? And then finally, how do we best treat these patients to optimize the chance that they will survive such a potentially deadly disease?” Moll asked.
Common cold virus linked to potentially fatal blood clotting disorder. University of North Carolina Health Care. EurekAlert! News release. Accessed August 10, 2023. Published August 10, 2023.