Platelet-activating functional assay resolution in vaccine-induced immune thrombotic thrombocytopenia: differential alignment to PF4 ELISA platforms

• Published in: Research and practice in thrombosis and haemostasis Vol. 7; no. 3; p. 100128
• Main Authors: Lee, Christine S.M., Clarke, Lisa J., Kershaw, Geoffrey W., Tohidi-Esfahani, Ibrahim, Brighton, Timothy A., Chunilal, Sanjeev, Favaloro, Emmanuel J., Tran, Huyen, Chen, Vivien M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-2023; Elsevier
• Subjects: Brief Report; COVID -19 vaccine; enzyme-linked immunosorbent assay; platelet activation; platelet factor 4; vaccine-induced immune thrombotic thrombocytopenia; vaccine-induced immune thrombotic thrombocytopenia; COVID -19 vaccine; platelet factor 4; platelet activation; enzyme-linked immunosorbent assay
• ISSN: 2475-0379; 2475-0379
• DOI: 10.1016/j.rpth.2023.100128

Anti-platelet factor 4 (PF4) antibodies in vaccine-induced immune thrombotic thrombocytopenia (VITT) appear to be transient, with discrepant persistence depending on the platform used for detection.
We aimed to report a longitudinal study of antibody persistence using 2 ELISA platforms and 2 platelet-activating functional assays in a clinical cohort of patients with VITT referred for follow-up testing.
In total, 32 Australian patients with VITT or pre-VITT, confirmed by expert adjudication, with samples referred for clinical follow-up were included. Clinical follow-up assays, including Stago and Hyphen ELISAs, procoagulant platelet flow cytometry, and modified PF4-serotonin-release assay, were performed according to the pattern of reactivity for that patient at diagnosis.
The median follow-up was 24 weeks after diagnosis. A general decline in anti-PF4 antibody levels and platelet-activating capacity over time was observed with a more rapid median time to resolution of 16 weeks by functional assay vs 24 weeks by Stago ELISA. Decline in platelet-activating antibody levels detected by functional assays mirrored Stago ELISA titer but not Hyphen. However, 87% of patients received a documented second vaccination and 74% received an mRNA booster with no reported adverse events.
Anti-PF4 antibodies persist longer than functional platelet-activating antibodies in VITT but do not warrant avoidance of subsequent vaccinations. Persistence detection is assay-dependent. Stago ELISA may be a surrogate where functional assays are unavailable for follow-up testing of confirmed patients with VITT.
•Antibodies in vaccine-induced immune thrombotic thrombocytopenia (VITT) decline over time.•Serial testing of patients with VITT is advised to guide treatment duration.•Platelet-activating antibodies resolved earlier than those detected by Stago or Hyphen ELISAs.•No adverse events were reported following subsequent vaccinations of patients after VITT diagnosis.