Anti-PF4 IgG levels in patients with VITT remain high at 7 months following vaccination and can still activate platelets

ABSTRACT

Background: Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a new syndrome that occurs 4-30 days following COVID-19 vaccination with adenoviral vector vaccines. VITT is characterised by thrombocytopenia, thrombosis, highly elevated levels of D-dimers and anti-platelet factor 4 (PF4) antibodies. Anti-PF4 antibodies activate platelets via FcgammaRIIA driving pathophysiology. However, the evolution of these antibodies and their ability to activate platelets after initial treatment remains unknown. Aim(s) To determine how anti-PF4 antibody levels in VITT patients change following recovery and the ability of patient serum to activate platelets. Method(s) We followed-up seven discharged VITT patients from diagnosis up to 280 days (range 199-280) post-vaccination and measured anti-PF4 antibodies and other biomarkers, including PF4 levels, in patient serum. We tested the ability of patient serum to activate healthy and patient platelets using light transmission aggregometry with and without PF4 addition. We also assessed platelet function of patients' platelets at the latest follow-up timepoint. Result(s) Anti-PF4 IgG antibody levels remained high in 6 out of 7 patients up to 7 months post-vaccination. The other patient received rituximab. Diagnostic patient serum strongly activated control (n = 3) and patient platelets, either alone or with PF4. Most follow-up serum alone (5 out of 7 patients) was weaker at stimulating platelets, despite similar anti-PF4 antibody levels. However, PF4-enhanced serum-mediated platelet activation was detectable in 3 out 7 patients beyond 150 days post-vaccination. Patients' PF4 serum levels were reduced at diagnosis compared to follow-up (p < 0.0001, n = 7) but returned to healthy control levels during follow-up. Patients' platelet responses and FcgammaRIIA levels were similar to controls. Conclusion(s) The reduction in serum-mediated platelet activation during follow-up, despite similar PF4 antibody levels remains unexplained. Further assessment is required to determine if levels of high affinity anti-PF4 antibodies are reduced during follow-up. Additional understanding is also required to assess duration of ongoing anticoagulation for VITT patients.