Semin Hematol 2022 Apr 20;59(2):59-71. Epub 2022 Feb 20.
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada; Transfusion Medicine, Hamilton Regional Laboratory Medicine Program, Hamilton, ON, Canada; Service of Benign Hematology, Hamilton Health Sciences, Hamilton General Hospital, Hamilton, ON, Canada; McMaster Center for Transfusion Research, McMaster University, Hamilton, ON, Canada. Electronic address:
Platelet factor 4 (PF4) is a highly cationic tetrameric protein that can be targeted by platelet-activating anti-PF4 antibodies of immunoglobulin G (IgG) class. Certain features of PF4, including its multivalent nature (duplicate antigen sites per tetramer), the ability of many PF4 tetramers to undergo close approximation through charge neutralization, and the dimeric binding of IgG molecules, results in formation of IgG-containing immune complexes in situ on platelets, neutrophils, and monocytes, resulting in Fcγ receptor-mediated pancellular activation that also activates hemostasis (potential for disseminated intravascular coagulation). This review discusses 4 anti-PF4 disorders: classic heparin-induced thrombocytopenia ([HIT]; triggered by heparin and certain other polyanionic pharmaceuticals, featuring predominantly heparin-dependent antibodies), autoimmune HIT (aHIT; severe subtype of HIT that features both heparin-dependent and heparin-independent platelet-activating antibodies), and spontaneous HIT (non-heparin triggers such as knee replacement surgery and infection; predominantly heparin-independent platelet-activating antibodies). Read More