Monoclonal gammopathy of thrombotic significance in a nutshell

This nutshell review discusses the pathophysiology, diagnostic features, treatment strategies and avenues for future research in a recently identified thrombotic entity, monoclonal gammopathy of thrombotic significance (MGTS). MGTS is an anti-platelet factor 4 (PF4) antibody-mediated disorder distinct from heparin-induced thrombocytopenia (HIT) and vaccine-induced thrombotic thrombocytopenia (VITT), as it involves the production of persistent, monoclonal anti-PF4 antibodies. Several subtypes of MGTS, including 'HIT-like', 'VITT-like' and 'non-HIT/VITT-like', exhibit unique serological profiles that can complicate diagnosis. Recognition of 'HIT-like' MGTS is critical to avoid heparin exposure in these patients, which can result in adverse effects like those seen in heparin-exposed HIT patients. 'Non-HIT/VITT-like' MGTS antibodies have only been detected in PF4-enhanced functional testing; therefore, we recommend using these platelet-based tests as the front-line assay for detecting MGTS antibodies. Mass profiling using mass spectrometry is critical for the 'fingerprinting' of monoclonal antibodies to establish a diagnosis of MGTS. Treatments used in HIT and VITT, such as non-heparin anticoagulants and intravenous immunoglobulin G, are typically insufficient for managing MGTS. Emerging MGTS therapies, such as plasma cell-directed drugs and Bruton tyrosine kinase inhibitors, are discussed. The review concludes with an emphasis on areas of future research in MGTS.