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

Abstract

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, CXCL4) cause platelet activation, which then lead to thrombocytopenia and thrombosis. VITT resembles the immune-mediated drug reaction heparin-induced thrombocytopenia (HIT); however, unlike HIT antibodies which have been shown to be transient, VITT antibodies appear to persist for much longer.

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 (EIA), as well as their ability to activate platelets in the PF4-serotonin release assay (PF4-SRA). The median latest follow-up was 715 days (range 126-1065 days) post-vaccination.

Results: Using Kaplan-Meier analysis, we found 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 VITT antibodies can persist for nearly 3 years in some patients and a proportion of those maintain their 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.