VITT-like Monoclonal Gammopathy of Thrombotic Significance, 2025, Jing Jing Wang, Ph.D et al

Summary
Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is associated with antibodies that target platelet factor 4 (PF4) and are heparin-independent. VITT antibodies are implicated in acute, transient prothrombotic disorders that are triggered by adenoviral vector vaccines against coronavirus disease 2019 or by adenovirus infection.

We describe chronic prothrombotic disorders featuring anticoagulant-refractory thromboses and intermittent thrombocytopenia that were associated with VITT-like antibodies in five patients (four patients with newly reported cases and the index patient). The patients had low levels of M proteins (median level, 0.14 g per deciliter); in each patient, we found that the M protein was the VITT-like antibody. The antibody clonotype profiles and binding epitopes on PF4 were different from those observed with the acute disorders occurring after vaccination or viral infection, features that reflect distinct immunopathogenesis.

Treatment strategies besides anticoagulation alone are needed for the chronic disorders, referred to as VITT-like monoclonal gammopathy of thrombotic significance. (Funded by the Canadian Institutes of Health Research and others.)
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New blood-clotting disorder identified by McMaster University researchers

“Our study highlights the importance of recognizing and diagnosing this new blood-clotting disorder,” said Theodore (Ted) Warkentin, co-first author and corresponding author of the study and professor emeritus in the Department of Pathology & Molecular Medicine at McMaster University.

“By understanding how to diagnose VITT-like MGTS, we can develop more effective treatment strategies that go beyond traditional anticoagulation,” said Warkentin, a hematologist in the Department of Medicine based at Hamilton Health Sciences’ Hamilton General Hospital.

Specialized testing was conducted at the McMaster Platelet Immunology Laboratory within the Michael G. DeGroote Centre for Transfusion Research, the only laboratory in Canada with the full repertoire of testing required to characterize the VITT-like antibodies that target the PF4 protein. Researchers performed a detailed analysis of cases exhibiting unusual blood-clotting despite patients being on full-dose blood thinners, focusing on those patients who had unexplained VITT-like antibodies that were detectable for a year or more.

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