Platelet factor 4 (PF4) is a cationic protein, able to form complexes with negatively charged molecules upon
its self-assembly into PF4 tetramers. The targeting of these PF4 complexes by IgG antibodies underlies
anti-PF4 disorders such as heparin-induced thrombocytopenia (HIT) and Vaccine-Induced Immune
Thrombocytopenia and Thrombosis (VITT)/ VITT-like disorders. The formation of IgG/PF4 immune
complexes facilitates uncontrolled activation of platelets, neutrophils and monocytes, via IgG-mediated Fcγ
receptor binding. This promotes the thrombosis and thrombocytopenia characteristic of anti-PF4 disorders.
HIT is predominantly triggered by heparin exposure. VITT is a recently recognised anti-PF4 disorder,
which developed following specific SARS-CoV-2 vaccinations. It is thought that hexon proteins,
components of adenoviral vectors, may form complexes with PF4 to trigger anti-PF4 antibody production
in VITT. A novel anti-PF4 disorder has been recognised causing platelet activation without administration
of heparin or SARS-CoV-2 vaccination and referred to as ‘VITT-like disorder.’ Clinical evaluation of HIT
and VITT/VITT-like disorders is based on thrombotic events, platelet counts, and D-dimer levels.
Laboratory assays such as heparin/PF4-induced platelet activation assays can be used to distinguish
between HIT and VITT. Treatment plans for HIT and VITT may differ across patient cases. In this review,
we discuss the pathogenesis, diagnosis and management of anti-PF4 disorders.