Antibodies to PF4 in severe COVID-19: same but different

Abstract

In this issue of Blood, Zhu et al1 find evidence of B-cell clones with the hallmarks of heparin-induced thrombocytopenia (HIT) specificity in a subset of patients with severe COVID-19 and platelet-activating antibodies. Given the shared pathogenesis of immunothrombosis, they looked for platelet factor 4 (PF4)/heparin antibodies in 130 patients hospitalized with severe COVID-19. As many as 80% of these patients demonstrated PF4/heparin immunoglobulin G (IgG) antibodies (optical density at 450 nm [OD450] >0.5), but only half of these displayed a functional capacity to activate platelets as measured by increased platelet surface P-selectin expression (PEA) after sensitization with a synthetic Toll-like receptor 9 (TLR-9) agonist motif cytosine triphosphate deoxynucleotide followed by a guanine triphosphate deoxynucleotide (PEACpG assay) Show more