A Rare, Chronic Disorder to Consider in Patients with Unexplained Thrombophilia

Vaccine-induced thrombocytopenia and thrombosis (VITT), also known as vaccine-induced immune thrombotic thrombocytopenia, is characterized by acute, transient thrombocytopenia triggered by vaccines for COVID-19 or, in some cases, adenovirus infection. VITT antibodies are generally transient, and tests becomes negative at a median of 16 weeks. VITT-like monoclonal gammopathy of thrombotic significance (MGTS) is a chronic prothrombotic disorder characterized by anticoagulant-refractory thromboses and intermittent thrombocytopenia, associated with VITT-like antibodies.

This report describes four new patients and one index patient with VITT-like MGTS, all of whom had recurrent thrombosis despite anticoagulation. The anti–platelet factor 4 (PF4) antibodies in patients with VITT-like MGTS have unique and binding epitopes on PF4, distinct from those seen in acute VITT triggered by vaccination or viral infection. The authors propose that patients with unexplained chronic prothrombotic disorders, even those without chronic thrombocytopenia, should be screened for PF4 antibodies and undergo serum protein electrophoresis and serum free light chain assays to evaluate for M proteins. Even a faint paraprotein band (<0.10 g/dL) may be clinically significant in the setting of anti-PF4 antibodies. Persistent detection of anti-PF4 antibodies as well as M protein over 3 months is required to confirm the diagnosis.