University Of North Carolina Discovers That Adenovirus Infections Can Cause Thrombocytopenia! Could New Strains Of Adenovirus Be At Play?

Adenovirus: In a groundbreaking discovery, researchers at the University of North Carolina School of Medicine-USA have unveiled a startling connection between adenovirus infections and a rare and potentially life-threatening blood clotting disorder. This revelation has sent shockwaves through the medical community, as it marks the first time that the widespread respiratory virus, typically associated with mild symptoms akin to the common cold and flu, has been implicated in blood clotting and severe thrombocytopenia.


 
The research team was spearheaded by Dr Stephan Moll and Dr Jacquelyn Baskin-Miller, both esteemed members of the UNC School of Medicine. Their study findings have not only shed new light on the virus's intricacies but also raised numerous questions about its implications for public health.
 
The Connection Between Adenovirus and Thrombocytopenia
Thrombocytes, or platelets, play a crucial role in the human body by forming blood clots that aid in healing wounds and injuries. A decrease in platelet count can lead to a condition known as thrombocytopenia, which can have severe consequences. This condition can be triggered by various factors, including viral infections and autoimmune diseases.
 
In this groundbreaking research, Dr Moll and Dr Baskin-Miller have established a strong connection between adenovirus infections and a unique blood clotting disorder known as an anti-platelet factor 4 disorder. These anti-PF4 disorders involve the body's immune system producing antibodies against platelet factor-4 (PF4), a crucial protein released by platelets. When these antibodies form and bind to PF4, it can set off a chain reaction leading to the rapid removal of platelets from the bloodstream, causing both blood clotting and low platelet counts.
 
Unraveling the Mystery of Spontaneous HIT and VITT
Interestingly, anti-PF4 disorders can manifest in different ways. In some cases, they are triggered by a patient's exposure to heparin, a condition known as heparin-induced thrombocytopenia (HIT). In other instances, anti-PF4 antibodies develop spontaneously without heparin exposure, leading to what researchers term "spontaneous HIT."

Recent years have witnessed a rare phenomenon where thrombocytopenia occurs after the administration of certain COVID-19 vaccines that utilize inactivated pieces of an adenoviral vector. This condition has been identified as vaccine-induced immune thrombotic thrombocytopenia (VITT). However, it's important to note that these vaccines differ from those developed in the United States, such as those by Moderna and Pfizer.
 
The Road to Discovery
The journey toward this groundbreaking discovery began with the case of a 5-year-old boy who was initially diagnosed with an adenovirus infection. However, his condition took a dire turn as he developed an aggressive blood clot in his brain, known as cerebral sinus vein thrombosis, along with severe thrombocytopenia. Intriguingly, the boy had not been exposed to heparin or received the adeno-vector COVID-19 vaccination, which are the typical triggers for HIT and VITT.
 
This puzzling c ase prompted a collaborative effort among medical professionals, with intensive care unit physicians, neuro-intensivists, and hematologists working tirelessly to save the young boy's life. Dr Baskin-Miller recalled, "He wasn't responding to therapy and was progressing quickly. We had questioned whether it could have been linked to his adenovirus considering the vaccine data, but there was nothing in the literature at that time to suggest it."
 
Recognizing the urgency and complexity of the situation, Dr Moll reached out to Dr Theodore E. Warkentin, a renowned expert in pathology and molecular medicine at McMaster University in Hamilton, Ontario. Dr Warkentin, who has spent three decades researching anti-PF4 disorders, was not aware of any association between adenoviral infections and spontaneous HIT.
 
Around the same time, Dr Moll received a call from Dr Alison L. Raybould, a hematologist-oncologist in Richmond, Virginia, and a former trainee at UNC. Dr Raybould had encountered a patient with multiple blood clots, a stroke, a heart attack, deep-vein thromboses in the arms and legs, and severe thrombocytopenia.
 
This patient had not been exposed to heparin or received vaccines but had tested positive for adenoviral infection. Testing for anti-PF4 antibodies yielded a positive result.
 
To gain more clarity on these diagnoses, Dr Warkentin offered to conduct further tests on the patients' blood samples in his laboratory at the Hamilton General Hospital. The results confirmed that the antibodies were targeting platelet factor 4, akin to the HIT antibodies. Astonishingly, the antibody shared similarities with those seen in VITT and bound to PF4 in the same region as VITT antibodies, leading to the conclusion that both patients had developed "spontaneous HIT" or a VITT-like disorder associated with adenovirus infection.
 
More Questions Than Answers
While this discovery has opened new avenues for understanding anti-PF4 disorders, it has also raised a plethora of questions that researchers are eager to address. Chief among these is the prevalence of the new anti-PF4 disorder and whether other viruses can trigger this condition. Additionally, researchers are keen to unravel why this disorder does not manifest in every adenovirus infection.
 
Dr Moll emphasized these pressing questions, saying, "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?"
 
There are also reasons to believe that newly evolved adenovirus strains could be at play here.
 
The study findings were published in the peer reviewed the New England Journal of Medicine.
https://www.nejm.org/doi/10.1056/NEJMc2307721
 
Adenovirus Diversity and Implications
Human adenoviruses are a diverse family of viruses, with nearly 60 different strains known to cause illnesses worldwide. Some strains, such as strain 7, have been associated with severe outbreaks, while others primarily cause digestive tract infections in young children. Understanding the range of adenovirus strains is crucial in comprehending the potential implications of this research.
 
Notably, different strains of adenovirus have varying levels of severity. For instance, types 2, 1, 3, 5, 7, and 6 are commonly isolated from adenovirus-infected children, with types 1 and 2 accounting for a significant portion of cases. However, adenovirus infections are responsible for only a small percentage of acute respiratory infections in children.
 
Among the adenovirus species, Adenovirus 7 (Ad7) has frequently been associated with severe illness. Research has identified seven distinct genome types of Ad7, each with unique characteristics. These genome types have evolved over time and exhibit regional variations in prevalence.
 
It's important to note that human adenoviruses are divided into seven species, with each species containing various serotypes. Different serotypes are associated with different conditions, including respiratory diseases, conjunctivitis, gastroenteritis, and even obesity. This diversity highlights the complexity of adenoviruses and their potential impact on human health.
 
When Thailand Medical News made proposals that perhaps new adenovirus strains were behind a mysterious hepatitis rise in children in 2022, we were ridiculed by the usual Western critics but subsequent studies confirmed that a new strain of adenovirus was indeed behind these occurrences!
https://www.nature.com/articles/d41586-023-00570-8
 
There is very genomic surveillance and monitoring of the evolution of various human adenoviruses and it may not be of any surprise that the adenovirus could have picked up mutations that changes its pathogenesis and now causing thrombocytopenia as well.
 
Thailand Medical News strongly believes that as a result of a change and major shift in the global immunity landscape as a result of SARS-CoV-2, various common pathogens are also evolving and mutating and spawning newer strains.
 
More studies are warranted on this hypothesis and also on the possibility that new adenovirus strains have already emerged and are behind the manifestations of thrombocytopenia.
 
With the coming Winter season expected to also see a rise in Adenovirus infections, more attention needs to be paid on clotting issues and thrombocytopenia in those infected.
 
For the latest on Adenovirus, keep on logging to Thailand Medical News.