Frequency of positive anti-PF4/polyanion antibody tests after COVID-19 vaccination with ChAdOx1 nCoV-19 and BNT162b2

Abstract

Vaccination using the adenoviral vector COVID-19 vaccine ChAdOx1 nCoV-19 (AstraZeneca) has been associated with rare vaccine-induced immune thrombotic thrombocytopenia (VITT). Affected patients test strongly positive in PF4/polyanion enzyme immunoassays (EIAs) and serum-induced platelet activation is maximal in the presence of PF4. We determined the frequency of anti-PF4/polyanion antibodies in healthy vaccinees and assessed whether PF4/polyanion EIA-positive sera exhibit platelet-activating properties after vaccination with ChAdOx1 nCoV-19 (n=138) or BNT162b2 (BioNTech/Pfizer; n=143). In total, 19 of 281 participants tested positive for anti-PF4/polyanion antibodies post-vaccination (All: 6.8% [95%CI, 4.4-10.3]; BNT162b2: 5.6% [95%CI, 2.9-10.7]; ChAdOx1 nCoV-19: 8.0% [95%CI, 4.5-13.7%]). Optical densities were mostly low (between 0.5-1.0 units; reference range, <0.50) and none of the PF4/polyanion EIA-positive samples induced platelet activation in the presence of PF4. We conclude that positive PF4/polyanion EIAs can occur after SARS-CoV-2 vaccination with both mRNA- and adenoviral vector-based vaccines, but the majority of these antibodies likely have minor (if any) clinical relevance. Accordingly, low-titer positive PF4/polyanion EIA results should be interpreted with caution when screening asymptomatic individuals after vaccination against Covid-19. Pathogenic platelet-activating antibodies that cause VITT do not occur commonly following vaccination.

Prevalence of thrombocytopenia, anti–platelet factor 4 antibodies and D‐dimer elevation in Thai people After ChAdOx1 nCoV‐19 vaccination

“…In the Norwegian and German cohorts, the frequencies of anti-PF4 Abs after ChAdOx1 vaccination were 1.2% (6/492 using OD ≥ 0.4, LIFECODES PF4 IgG ELISA, Immucor, Waukesha, WI, USA) and 8.0% (11 of 138 using OD ≥ 0.5, an inhouse IgG-specific PF4/polyanion enzyme immunoassay). 12,13 The anti-PF4 Abs in most VITT cases had very high OD values (>2.0). 4 6 Recent studies demonstrated that different ELISA assays (Zymutest, LIFECODES, and Asserachrom) provided excellent VITT diagnostic performance with a sensitivity of >90%.…”

Antibody epitopes in vaccine-induced immune thrombotic thrombocytopaenia

“…Other cells, including monocytes, are also activated by these immune complexes, which amplifies the hypercoagulable state in HIT patients 11 . It has been postulated that VITT has a similar pathophysiology to HIT, and several investigators have demonstrated the presence of high levels of anti-PF4 antibodies in VITT samples [1][2][3]12 . However, VITT is a unique syndrome since it occurs without heparin exposure, and the pattern of platelet reactivity, in vitro, does not demonstrate typical heparin-dependence, as seen with HIT.…”

Prevalence of anti-platelet factor4/polyanionic antibodies after COVID-19 vaccination with ChAdOx1 nCoV-19 and CoronaVac in Thais

“…The copyright holder for this preprint this version posted July 19, 2021. ; https://doi.org/10.1101/2021.07.15.21260622 doi: medRxiv preprint demonstrated a higher frequency of anti-PF4 antibodies among vaccinees receiving ChAdOx1 nCoV-19 (8.0%) [5]. It also demonstrated seroconversion of anti-PF4 in 2 out of 6 available samples while preexisting antibodies were found in the other 4 available samples.…”

“…The anti-PF4/polyanion antibodies were also negative in all participants in the control group in that study. However, a study from Germany demonstrated a higher frequency of anti-PF4 antibodies among vaccinees receiving ChAdOx1 nCoV-19 (8.0%) [5]. It also demonstrated seroconversion of anti-PF4 in 2 out of 6 available samples while preexisting antibodies were found in the other 4 available samples.…”