Platelet Factor 4 and Corresponding Antibodies in Atherosclerosis and Cardiovascular Disease

Antibodies directed against platelet factor 4 (PF4) are increasingly recognized as key mediators of immunothrombosis. In heparin-induced thrombocytopenia (HIT), these antibodies emerge following exposure to the polyanion heparin, whereas in vaccine-induced immune thrombocytopenia and thrombosis (VITT), they arise in response to vector-based vaccination or (adeno)viral infections. In both settings, anti-PF4 antibodies promote platelet activation and enhance inflammatory and thrombotic processes. PF4 itself has also been implicated in atherosclerosis and cardiovascular disease (CVD), although clinical studies investigating this link have yielded inconsistent results. We review the current knowledge on the roles of PF4 and anti-PF4 antibodies in atherosclerosis and CVD and discuss preclinical and clinical evidence for their relevance in the perioperative setting, for disease progression and antiplatelet therapy.