Persistence of anti-platelet factor 4 antibodies in vaccine-induced immune thrombocytopenia and thrombosis for 3 years

BACKGROUND: Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare and potentially life-threatening complication of adenoviral vector-based vaccines against SARS-CoV-2. In VITT, antibodies against platelet factor 4 (PF4; ie, CXCL4) cause platelet activation, which then leads to thrombocytopenia and thrombosis. VITT resembles the immune-mediated drug reaction of heparin-induced thrombocytopenia; however, unlike heparin-induced thrombocytopenia antibodies, which have been shown to be transient, VITT antibodies appear to persist for much longer. OBJECTIVE(S): To identify the clinical outcomes and laboratory testing features of VITT patients beyond the acute phase of disease. METHODS: In this study, we followed a Canadian cohort of VITT patients (N = 30) for nearly 3 years from their initial presentation and report serial testing for anti-PF4 antibody levels by enzyme immunoassay, as well as the ability to activate platelets in the PF4-serotonin release assay. The median latest follow-up time was 715 days (range, 126-1065) post-vaccination. RESULTS: Using Kaplan-Meier analysis, we found that 65.2% of VITT patients continued to test positive for anti-PF4 antibodies, and 34.1% of patients continued to test positive for platelet-activating anti-PF4 antibodies. There were no cases of recurrent thrombosis; however, 7/8 (87.5%) VITT patients with persistent platelet-activating anti-PF4 antibodies remained on anticoagulant or antiplatelet therapy. CONCLUSION: Our findings demonstrate that VITT antibodies can persist for nearly 3 years in some patients, and a proportion of those maintain the ability to activate platelets in vitro. The complete duration of VITT antibody persistence remains unknown, and whether this has clinical implications requires ongoing surveillance with further evaluation.