Red-colored region depicts region on platelet factor 4 (PF4) molecule recognized by VITT-like antibodies obtained from patient 2 (adult). Credit: Mercy Daka and Ishac Nazy.
Working with two patients harboring a life-threatening disorder without a name, researchers and clinicians have uncovered a very surprising biological link: adenovirus infection, or the common cold.
In a new case study published in the New England Journal of Medicine, researchers at the UNC School of Medicine have linked adenovirus infection with a rare blood clotting disorder. This is the first time that the common respiratory virus has been reported to be associated with blood clots and severe thrombocytopenia, which is when infections cause platelet levels to drop throughout the body.
Thanks to the research, the adenovirus-associated disorder is now one of four recognized anti-PF4 disorders. In anti-PF4 disorders, a person’s immune system makes antibodies against platelet factor-4 (PF4), a protein that is released by platelets. When an antibody forms against PF4 and binds to it, this can trigger the activation and rapid removal of platelets in the bloodstream, leading to blood clotting and low platelets, respectively.
The formation of anti-PF4 antibodies is most commonly triggered by a patient’s exposure to the medication heparin, an anticoagulant. Beside heparin-induced thrombocytopenia (HIT), the disorder can sometimes also occur as an autoimmune condition without heparin exposure, which is referred to as spontaneous HIT.
That’s what Jacquelyn Baskin-Miller, MD, ended up diagnosing an ill 5-year-old boy with when he admitted to the hospital. The boy had originally presented to the hospital as an outpatient with adenovirus infection, but then had to be admitted with an aggressive blood clot forming in his brain and severe thrombocytopenia. Doctors confirmed the boy had not been exposed to heparin.
Around the same time, Baskin-Miller and collaborator Stephan Moll, MD, received a call from Alison Raybould, MD, a former trainee who became a hematologist-oncologist in Virginia. Raybould had a patient with multiple blood clots, a stroke and heart attack, arm and leg deep-vein thromboses, and severe thrombocytopenia. But this patient hadn’t been exposed to heparin, either.
To help clarify the diagnoses of the two patients, researchers at McMaster University further tested the patients’ blood. The Canadian team confirmed that the antibodies were targeting platelet factor 4, much like the HIT antibodies. They concluded that both patients had spontaneous HIT, associated with an adenovirus infection.
These two cases represent the first time adenovirus infection has been associated with blood clots and life-threatening thrombocytopenia. And although it opens many new research doors, it also leaves more questions than answers.
Can the disorder be caused by other viruses? Why doesn’t it occur with every adenovirus infection? What degree of thrombocytopenia raises the threshold to test for anti-PF4 antibodies? What preventative measures can be made to help patients who develop the potentially deadly anti-PF4 disorder? And finally, what is the best way to treat patients with the disorder to optimize the chance or survival?