Article Impact Level: HIGH Data Quality: STRONG Summary of New England Journal of Medicine, NEJMoa2415930. https://doi.org/10.1056/NEJMoa2415930 Dr. Jing Jing Wang et al.
Points
- Researchers at McMaster University have identified a novel chronic blood clotting disorder known as VITT-like monoclonal gammopathy of thrombotic significance (MGTS), which shares similarities with vaccine-induced immune thrombocytopenia and thrombosis (VITT).
- In contrast to acute VITT, MGTS is a chronic condition characterized by persistent thromboses that do not respond to anticoagulant therapy, recurrent low platelet levels, and the presence of VITT-like antibodies that target platelet factor 4 (PF4). It includes low levels of monoclonal (M) protein along with unique immunopathogenic characteristics.
- The research analyzed five global cases involving patients who exhibited VITT-like symptoms for more than 12 months, even while receiving full-dose anticoagulation therapy. Intravenous immunoglobulin (IVIG), Bruton tyrosine kinase inhibitors (ibrutinib), and therapies targeting plasma cells demonstrated favorable outcomes.
- The results indicate that standard anticoagulants might not be effective for MGTS patients, highlighting the necessity for novel treatment approaches specifically designed for this uncommon clotting condition.
- Gaining insights into VITT-like MGTS improves the diagnosis and treatment of recurrent or unexplained blood clots, offering a deeper understanding of abnormal clotting mechanisms and enhancing the clinical management of those impacted.
Summary
Researchers at McMaster University have identified a new blood clotting disorder that resembles vaccine-induced immune thrombocytopenia and thrombosis (VITT), which has been named VITT-like monoclonal gammopathy of thrombotic significance (MGTS). This condition is characterized by ongoing thromboses that are resistant to anticoagulant treatment and episodes of thrombocytopenia in affected individuals, along with the presence of VITT-like antibodies that target platelet factor 4 (PF4). In contrast to the acute VITT cases linked to COVID-19 vaccination, this chronic condition is characterized by low levels of monoclonal (M) proteins, with a median level of 0.14 g/dL. The antibodies linked to thrombotic events show unique clonotype profiles and PF4 binding epitopes, indicating a distinct immunopathogenesis when compared to acute VITT.
The research examined data from five patients located in Canada, New Zealand, France, Spain, and Germany, each exhibiting prolonged VITT-like antibody reactivity lasting more than 12 months. Patients exhibited irregular blood clotting even while receiving full-dose anticoagulation treatment. Notably, the patients showed positive responses to various alternative treatments, such as high-dose intravenous immunoglobulin (IVIG), Bruton tyrosine kinase inhibitors (ibrutinib), and therapies aimed at targeting plasma cells in myeloma. The results suggest that conventional anticoagulants might not be suitable for addressing this condition, highlighting the need for innovative treatment approaches to care for these patients.
The findings of this study carry important clinical relevance, emphasizing the need for accurate diagnosis and treatment of this emerging disorder, potentially enhancing the management of patients experiencing recurrent or unexplained blood clots. Identifying VITT-like MGTS allows healthcare professionals to investigate treatment alternatives beyond anticoagulation therapy, which may enhance outcomes for patients with this uncommon and persistent condition. The findings enhance our comprehension of the mechanisms behind abnormal blood clotting, providing valuable insights for innovative patient care strategies.
Link to the article: https://www.nejm.org/doi/10.1056/NEJMoa2415930
References Wang, J. J., Warkentin, T. E., Schönborn, L., Wheeler, M. B., Geerts, W. H., Costedoat-Chalumeau, N., Gendron, N., Ene, G., Lozano, M., Langer, F., Lindhoff-Last, E., Budde, K., Chataway, T., Troelnikov, A., Sheppard, J.-A. I., Zhang, Y., Arnold, D. M., Gordon, T. P., Thiele, T., … Nazy, I. (2025). Vitt-like monoclonal gammopathy of thrombotic significance. New England Journal of Medicine, NEJMoa2415930. https://doi.org/10.1056/NEJMoa2415930
