Healthcare (Commonwealth Union) – Scientists specializing in hematology at McMaster University in Canada, have made a significant breakthrough, uncovering the reason behind unexpected and persistent blood clotting that occurs even when patients are treated with high-dose anticoagulants.
Their findings, recently published in The New England Journal of Medicine, are poised to reshape how medical professionals diagnose and manage unusual or recurrent clotting disorders, with the potential to enhance patient care.
The researchers identified a newly recognized blood clotting condition that shares key characteristics with vaccine-induced immune thrombocytopenia and thrombosis (VITT)—a rare but severe clotting disorder linked to certain COVID-19 vaccines that are no longer in use.
The study highlights that some individuals can develop serious blood clotting due to antibodies that mimic those responsible for VITT, even without common triggers such as blood thinners (heparin) or prior vaccination.
This newly classified disorder has been named VITT-like monoclonal gammopathy of thrombotic significance (MGTS).
Theodore (Ted) Warkentin, the study’s co-first and corresponding author, who serves as professor emeritus in the Department of Pathology & Molecular Medicine at McMaster University indicated that their study revealed that it is crucial to identify and diagnose this emerging blood-clotting condition.
Warkentin, a hematologist in the Department of Medicine at Hamilton Health Sciences’ Hamilton General Hospital stated that recognizing and accurately diagnosing VITT-like MGTS is crucial to developing more advanced treatment approaches that extend beyond standard anticoagulant therapy.
Comprehensive testing took place at the McMaster Platelet Immunology Laboratory, housed within the Michael G. DeGroote Centre for Transfusion Research. This facility is the only one in Canada equipped with the full range of tests needed to identify and analyze the VITT-like antibodies that specifically target the PF4 protein.
Scientists conducted an in-depth examination of cases where patients continued to experience abnormal blood clotting despite receiving full-dose anticoagulants. Their focus was on individuals with unexplained VITT-like antibodies that remained present for at least a year or more.
The investigation revealed the existence of M (monoclonal) proteins—markers commonly associated with plasma cell disorders. The persistence of these VITT-like immune responses for over 12 months, an unusual characteristic for most anti-PF4 antibodies, suggested an ongoing disease process rather than a temporary immune reaction.
The research was conducted through an international collaboration, gathering data from five patients who received treatment at medical institutions in Canada, New Zealand, France, Spain, and Germany.
Jing Jing Wang of Flinders University in Australia played a key role in confirming that the M proteins in each patient were the disease-causing VITT-like antibodies. Meanwhile, Andreas Greinacher from Greifswald University in Germany contributed by identifying additional similar cases through his anti-PF4 reference laboratory.
“The findings of this study underscore our ability to leverage fundamental molecular and biochemical science to unravel disease mechanisms,” explained the co-lead author Ishac Nazy, director of the McMaster Platelet Immunology Laboratory as well as co-director of the Michael G. DeGroote Centre for Transfusion Medicine.
“This approach enables precise patient diagnosis and informs timely treatment strategies, even for previously unidentified diseases, exemplifying true bench-to-bedside translational medicine,” says Nazy, who is an associate professor in the department of Medicine at the McMaster University.
An important finding was that all the patients did not respond to standard blood-thinning treatments. However, they experienced some improvement with alternative therapies, including high-dose intravenous immunoglobulin (IVIG), Bruton tyrosine kinase inhibitors (ibrutinib), and treatments targeting plasma cells used for myeloma.
The identification of this new blood clotting disorder carries significant implications for how medical professionals diagnose and manage patients with unusual or treatment-resistant blood clots in the future.
This research received financial support from the Canadian Institutes of Health Research (CIHR), the Public Health Agency of Canada, and the Heart and Stroke Foundation of Canada.
