Platelet factor 4 antibody persistence and long-term pathogenicity in vaccine-induced immune thrombotic...

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a transient prothrombotic process, although recent data suggest that VITT anti-platelet factor 4 (PF4) antibodies are more persistent than those in heparin-induced thrombocytopenia.

We sought to interrogate whether anti-PF4 antibody persistence in VITT is related to the continued persistence of antibody clones from the acute phase or to the development of novel anti-PF4 antibodies due to epitope spreading.

Samples from 6 patients with Ad26.COV2.S-associated VITT with a median time to follow-up of 244 days from acute presentation (range, 114-664 days) were studied in antigenic/functional assays and by mass spectrometry. One patient with ChAdOx1 nCoV-19-associated VITT was tested >4 years after acute presentation.

Upon affinity-enrichment of anti-PF4 antibodies, mono/oligoclonal anti-PF4 antibodies were observed despite negative results in serum protein electrophoresis/"Mass-Fix" testing of native sera. Anti-PF4 antibody abundance decreased over time, with no evidence of novel anti-PF4 antibody production after acute presentation. Although previous studies indicate a stereotypical pairing of VITT antibodies with lambda light chains, 1 patient with VITT produced antibodies with a kappa light chain. Long-term thrombocytopenia/thrombosis was not seen in any of the 6 Ad26.COV2.S-associated VITT patients; however, platelet-activating anti-PF4 antibodies were seen 4 years after the acute event in an additional patient with ChAdOx1 nCoV-19-associated VITT with chronic low-grade thrombocytopenia.

VITT, unlike monoclonal gammopathy of thrombotic significance, appears to be a monoclonal gammopathy of unknown significance-negative state, but it needs confirmation in larger studies. VITT antibodies can be composed of lambda or kappa light chains, and some patients with VITT exhibit persistent thrombocytopenia many years after the acute event.