Researchers have linked adenoviruses to a rare blood clotting disorder, expanding knowledge about the causes of severe thrombocytopenia and prompting further research into its treatment and prevalence.
Platelets, or platelets, are specialized cell fragments that form blood clots when you suffer an abrasion or trauma. Conditions such as viral infections, autoimmune diseases, etc. can cause the number of platelets in the body to drop, a condition known as thrombocytopenia.
Through an extensive clinical research partnership, Dr. Stephan Moll and Dr. Jacquelyn Baskin-Miller of the UNC School of Medicine identified a link between adenovirus infections and rare blood clotting disorders. The discovery marks the first time a respiratory disease has become widespread. virusis known to cause mild symptoms similar to colds and flu, but is thought to be involved in blood clotting and severe thrombocytopenia.
“This adenovirus-associated disease is one of four currently recognized anti-PF4 diseases,” said Professor Mol, from the School of Medicine’s Department of Hematology. “We hope that our findings will lead to earlier diagnosis, appropriate and optimized treatment, and better outcomes for patients who develop this life-threatening disease.”
Dr. Stephen Mohr.Credit: UNC Blood Research Center
Their new observations are New England Medical Journal, Sheds new light on viruses and their role in causing antiplatelet factor 4 disorders. Additionally, this discovery opens a whole new door for research, as many questions remain about how and why this condition occurs and who is most likely to develop this disorder.
HIT, VITT, and “spontaneous HIT”
Antibodies are large Y-shaped proteins that attach to the surface of bacteria or other “foreign objects” and can alert the immune system to destruction or directly neutralize the threat.
In anti-PF4 disease, a person’s immune system creates antibodies against platelet factor 4 (PF4), a protein released by platelets. The formation and binding of antibodies against PF4 causes activation and rapid removal of platelets from the bloodstream, which can lead to blood clotting and platelet reduction, respectively.
The formation of anti-PF4 antibodies can be caused by a patient’s exposure to heparin, called heparin-induced thrombocytopenia (HIT), or it can occur as an autoimmune disease without heparin exposure. is called “spontaneous HIT.”
Over the past 3 years, it has been shown that thrombocytopenia rarely occurs after injection. COVID-19 (new coronavirus infection) A vaccine made from an inactivated portion of an adenovirus vector. These vaccines are different from those made in the United States, such as Moderna and Pfizer. This condition is called vaccine-induced immune thrombotic thrombocytopenia (VITT).
path to discovery
The path to the discovery was that a 5-year-old boy diagnosed with adenovirus infection at an outpatient clinic was diagnosed with a progressive blood clot (called cerebral sinus vein thrombosis) that had formed in his brain and severe thrombocytopenia. It started with me having to be hospitalized. . Doctors determined that he had not been exposed to the coronavirus vaccination with heparin or adenovector, which are classic triggers for HIT and VITT.
“Intensive care unit physicians, neurointensivists, and hematology groups worked around the clock to determine the next steps in this boy’s care,” said Dr. Baskin-Miller. “He was not responding to treatment and was rapidly progressing. We were wondering if it could be related to his adenovirus, given the vaccine data. However, there was nothing in the literature of the time to suggest this.
Collaborative clinical efforts to help patients expanded. Mr. Baskin-Miller reached out to Mr. Moll, who is an expert in thrombosis and has various connections throughout the field. To Mohr, it appeared that the pediatric patient might have a “spontaneous HIT.” He then tested for HIT platelet-activating antibodies, which came back positive.
collaboration is key
Professor Moll reached out to Theodore E. Warkentin, MD, professor of pathology and molecular medicine at McMaster University in Hamilton, Ontario, who has been researching anti-PF4 disease for 30 years, to investigate the association between adenoviruses and adenoviruses. I asked them if they were aware of their gender. Infection and spontaneous HIT. Warkentin is one of the leading international researchers of anti-PF-4 disorders, but he didn’t know about the disease.
Around the same time, Mohr received a call from Allison L. Raybould, M.D., a hemato-oncologist in Richmond, Virginia, and a former UNC resident. She was seeing patients with multiple blood clots, strokes and heart attacks, 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 symptoms also began with viral symptoms of cough and fever, and he tested positive for adenovirus infection. A test for anti-PF4 antibodies also turned out to be positive.
In order to clarify the diagnosis of the two patients, Dr. Warkentin immediately suggested further testing of the patients’ blood and the samples were sent directly to his laboratory at Hamilton General Hospital for further research. Ta. They confirmed that the antibody targeted platelet factor 4, similar to his HIT antibody.
Remarkably, this antibody was similar to that of VITT and bound to PF4 in the same region as the VITT antibody. They concluded that both patients had “spontaneous HIT” or VITT-like disease associated with adenovirus infection.
Ask more questions
Following these groundbreaking conclusions, Moll et al. are now investigating the prevalence of the new anti-PF4 disease, whether this condition can be caused by other viruses, and why this condition is unique to adenoviruses. Many questions remain, including whether this does not happen every time there is an infection.
They also wonder what preventative measures and treatments can be used to help patients who develop the new, potentially deadly anti-PF4 disease.
“How common is this disorder?” Mol asked. “How much thrombocytopenia would raise the threshold for testing for anti-PF4 antibodies? And finally, to give these patients the best chance of surviving such a potentially fatal disease? What is the best way to treat it?”
Reference: “Adenovirus-associated thrombocytopenia, thrombosis, and VITT-like antibodies” by Theodore E. Warkentin, Jacquelyn Baskin-Miller, Alison L. Raybould, Jo-Ann I. Sheppard, Mercy Daka, Ishac Nazy, and Stephan Moll. , August 10, 2023, New England Medical Journal.
DOI: 10.1056/NEJMc2307721
