Thrombocytes, or blood platelets, are specialized cell formations that form blood clots when we have scratches and traumatic injuries to help blood clot and heal. Viral infections, autoimmune diseases and other conditions can cause a decrease in platelet levels throughout the body, a condition known as thrombocytopenia. In rare cases, the number of platelets can be so low that dangerous internal bleeding can occur, including in the brain, which can cause death.
Two researchers at the University of North Carolina (UNC) School of Medicine, Dr. Stephan Moll and Dr. Jacquelyn Baskin-Miller, have linked adenovirus infection to a rare blood clotting disorder.
This is the preceding that this common respiratory virus, which causes mild cold and flu symptoms, has been reported to be associated with blood clots and severe thrombocytopenia.
“This adenovirus-associated disorder is now one of four recognized anti-PF4 disorders,” said Dr. Stephan Moll, professor of medicine in the department of hematology at UNC.
The researchers hope that the results will lead to earlier diagnosis, appropriate and optimized treatment and better outcomes for patients who develop this life-threatening disease.
The research, published Thursday in the medical journal New England Journal of Medicine – NEJMshed new light on the virus and its role in causing a factor 4 coagulation disorder.
In addition, the discovery opens new research horizons, as many questions remain, currently unanswered, regarding how and why this condition occurs – and who is the person most prone to develop this condition.
Heparin-induced thrombocytopenia (HIT) and “spontaneous HIT”
Antibodies are large Y-shaped proteins that can remain on the surface of bacteria and other “foreign” substances, marking them for destruction by the immune system, or neutralizing the threat directly.
In anti-PF4 disease, the person’s immune system produces antibodies against platelet factor-4 (PF4), a protein that comes from platelets.
When an antibody forms against PF4 and binds to it, it can trigger the activation and rapid removal of platelets from the blood, leading to blood clotting and low platelet levels.
Sometimes the formation of anti-PF4 antibodies is triggered by a patient’s exposure to heparin, which is called heparin-induced thrombocytopenia (HIT), and other times it occurs as an autoimmune condition without exposure to heparin, which is called “spontaneous HIT.”
In the last three years, it has been shown that thrombocytopenia can occur, in rare cases, after injections with the vaccines against Covid-19, made with inactivated fragments of an adeno-viral vector.
These vaccines differ from those manufactured in the United States, such as those produced by Moderna and Pfizer with messenger RNA (mRNA).
The condition is called immune-mediated thrombocytopenia (VTT).
The road to this discovery
It all started when a 5-year-old boy diagnosed with an adenovirus infection in an outpatient setting had to be admitted to the hospital with an aggressive blood clot forming in the brain (called cerebral sinus vein thrombosis) and severe thrombocytopenia.
Doctors determined that he had not been exposed to heparin or the adeno-vector vaccine against Covid-19, the classic triggers for TIH and TTIV.
Doctors in the intensive care unit, the neuro-intensivist and the hematology group worked around the clock to determine the next steps in this boy’s care, said Dr. Jacquelyn Baskin-Miller.
The boy did not respond to therapy and his condition rapidly deteriorated.
“We asked if it could be related to his adenovirus, given the vaccine data, but there was nothing in the literature at the time to suggest this,” the doctor said.
Collaborative clinical efforts to help the patient increase. Dr. Baskin-Miller contacted Dr. Moll, who is an expert in thrombosis and has many connections in this field.
Dr. Moll suspected that the pediatric patient might be suffering from “spontaneous IHT.”
The two doctors tested the platelet-activating antibody TIH, which came out positive.
In the medical field, collaboration is essential
Dr. Moll contacted Dr. Theodore E. Warkentin, professor of pathology and molecular medicine at McMaster University in Hamilton, Ontario, Canada, who has researched anti-PF4 disease for three decades, to see if he knew of an association between adenovirals. infection and spontaneous HIT.
Dr. Warkentin, who is one of the leading international researchers in the field of anti-PF-4 disease, was not aware of this condition.
Around the same time, Dr. Moll received a call from Dr. Alison L. Raybould, a hematologist-oncologist in Richmond, Va., and former UNC intern.
He saw a patient with multiple blood clots, a stroke and myocardial infarction, deep vein thrombosis (DVT) in the arms and legs, and severe thrombocytopenia.
The patient has not been exposed to heparin or Covid vaccines.
nonetheless, this patient’s severe illness also began with viral symptoms of cough and fever and tested positive for adenoviral infection.
Testing for an anti-PF4 antibody was also positive.
To help clarify the diagnosis of the two patients, Dr. Warkentin immediately offered more tests on the patients’ blood, and the samples were sent directly to his laboratory at Hamilton General Hospital for further study.
They confirmed that the antibodies target platelet factor 4, as do the TIH antibodies.
Surprisingly, the antibody was similar to that of TTIV and bound to PF4 in the same region as the TTIV antibodies.
Doctors concluded that both patients had “spontaneous HIT”, or a disease similar to TTIV, associated with an adenovirus infection.
More questions
After such a breakthrough finding, Dr. Moll and his colleagues are now left with many questions about the prevalence of the new anti-PF4 disease, whether the condition can be caused by other viruses, and why this condition does not occur with every adenovirus infection. .
Doctors are also wondering what preventative measures or treatments can be taken to help patients who develop the new, potentially fatal anti-PF4 disease.
“How common is this disease?” Dr. Moll asked. “What degree of thrombocytopenia raises the threshold for testing for anti-PF4 antibodies? So, ultimately, how can we best treat these patients to optimize their chances of surviving such a potentially fatal disease?
Future research is needed to answer these questions, the doctor said.
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