Abstract
Anti-platelet factor 4 (PF4) antibody-mediated disorders are a heterogeneous group
of diseases characterized by the presence of highly pathogenic immunoglobulins G directed
against PF4 and/or PF4/heparin complexes. These antibodies are able to activate platelets,
neutrophils, and monocytes, thus resulting in thrombocytopenia and a hypercoagulable
state. Five different forms of anti-PF4 antibody-mediated disorders have been identified:
(1) classic heparin-induced thrombocytopenia (HIT) mediated by heparin and certain
polyanionic drugs; (2) autoimmune HIT characterized by the presence of anti-PFA/polyanion
antibodies that can strongly activate platelets even in the absence of heparin; (3)
spontaneous HIT characterized by thrombocytopenia and thrombosis without proximate
exposure to heparin, with two subtypes: (a) post-total knee arthroplasty and cardiac
surgery using cardiopulmonary bypass or extracorporeal membrane oxygenation and (b)
postinfections; (4) vaccine-induced immune thrombotic thrombocytopenia (VITT) characterized
by thrombocytopenia, arterial and venous thrombosis, or secondary hemorrhage after
receiving adenoviral vector vaccines for coronavirus disease 2019; (5) VITT-like disorders
triggered by adenoviral infections. Although extremely rare and largely unknown, there
has been growing interest in the VITT syndrome in recent years due to its clinical
relevance. Timely detection of these antibodies is crucial for the diagnosis and treatment
of anti-PF4 antibody-mediated disorders, via anti-PF4 antibody immunoassays using
several antibody capture systems (e.g., enzyme-linked immunosorbent assay-based, particle
gel, turbidimetry) and functional assays (e.g., serotonin release assay or heparin-induced
platelet activation). We aimed to present the latest on laboratory findings, clinical
characteristics, and therapeutic approaches for anti-PF4 antibody-mediated disorders.
Keywords
anti-PF4 antibody-mediated disorders - heparin-induced thrombocytopenia - VITT
