Recent advances in classic heparin-induced thrombocytopenia (HIT), autoimmune HIT, spontaneous HIT, and vaccine-induced immune thrombotic thrombocytopenia

Anti-PF4 disorders are a group of platelet-consumptive disorders characterized by platelet-activating antibodies against platelet factor4 (PF4), thrombocytopenia and an increased risk of thrombosis. PF4 is a chemokine released by platelet alpha granules upon activation, which can form immune complexes with negatively charged substances, such as heparin, cartilage components, nucleic acids, and viral and bacterial agents. Antibodies formed in response to PF4-polyanion complexes may display platelet-activating properties and cause pan-cellular activation, leading to the marked prothrombotic state of anti-PF4 disorders. In recent years, the landscape of anti-PF4 disorders has evolved to include classic heparin-induced thrombocytopenia (cHIT), autoimmune HIT (aHIT), spontaneous HIT (SpHIT), vaccine-induced immune thrombotic thrombocytopenia (VITT), and the newly recognized spontaneous VITT (SpVITT). These disorders havegarnered increased attention due to their association with severe clinical outcomes. Recent discoveries have expanded the understanding of these conditions, highlighting the role of various triggers, such as upper respiratory tract infections and monoclonal gammopathy of undetermined significance, in their development. Compared to cHIT, the less common anti-PF4 disorders VITT, aHIT, SpHIT and SpVITTgenerally appear more severe, with aggressive disease courses,more severe thrombocytopenia and a higher frequency ofbleeding, thrombosis at unusual sites, involvement of the centralnervous system and of multiple vascular beds. Clinical suspicionand knowledge of the less well-known triggers of anti-PF4disorders are pivotal to ordering the appropriate laboratory testsand initiating the necessary treatments. Herein, we will reviewcHIT, aHIT, SpHIT and VITT, focusing on their clinicalpresentation and therapeutic management.