TY - JOUR
T1 - Platelet-activating functional assay resolution in vaccine-induced immune thrombotic thrombocytopenia
T2 - differential alignment to PF4 ELISA platforms
AU - Lee, Christine S.M.
AU - Clarke, Lisa J.
AU - Kershaw, Geoffrey W.
AU - Tohidi-Esfahani, Ibrahim
AU - Brighton, Timothy A.
AU - Chunilal, Sanjeev
AU - Favaloro, Emmanuel J.
AU - Tran, Huyen
AU - Chen, Vivien M.
N1 - Funding Information:
The authors acknowledge the members of the THANZ VITT advisory group and the THANZ VITT ELISA group. They greatly appreciate Diane Criminale and the staff at the CRGH Blood Collection Unit for assistance in blood collection. This study is partly funded by NSW Health Pathology. V.M.C. was funded by a NSW Ministry of Health Senior Clinician Scientist Cardiovascular Capacity Building Grant. Blood collection from healthy volunteers and comparison of assays were approved by the Sydney Local Health District Human Research Ethics Committees (HREC/18/CRGH/294, X21-0160, 2021/ETH00945, and 2021/ETH11929). Healthy blood donors for functional assays gave written informed consent. C.S.M.L. designed and performed the experiments, analyzed the data, and wrote the manuscript. G.W.K. provided the ELISA results. T.B. provided the serotonin-release assay data. L.C. I.T-E. S.C. E.J.F. and H.T. collected clinical and ELISA information. V.M.C. designed and supervised the study, collected clinical information, analyzed data, and wrote the manuscript. All authors helped revise the manuscript and approved its submission. V.M.C. holds a US patent “Selective targeting of procoagulant platelets” US15/521435. C.S.M.L. and V.M.C. hold International (PCT) Patent Application No. PCT/AU2021/051233 for “Identification of prothrombotic conditions.” All the authors declare no competing financial interests. Data will be made available upon reasonable request.
Funding Information:
This study is partly funded by NSW Health Pathology . V.M.C. was funded by a NSW Ministry of Health Senior Clinician Scientist Cardiovascular Capacity Building Grant.
Publisher Copyright:
© 2023 The Authors
PY - 2023/3
Y1 - 2023/3
N2 - BackgroundAnti-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.ObjectivesWe
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.MethodsIn
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.ResultsThe
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.ConclusionAnti-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.
AB - BackgroundAnti-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.ObjectivesWe
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.MethodsIn
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.ResultsThe
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.ConclusionAnti-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.
KW - COVID -19 vaccine
KW - enzyme-linked immunosorbent assay
KW - platelet activation
KW - platelet factor 4
KW - vaccine-induced immune thrombotic thrombocytopenia
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U2 - 10.1016/j.rpth.2023.100128
DO - 10.1016/j.rpth.2023.100128
M3 - Article
C2 - 37122532
AN - SCOPUS:85152283928
SN - 2475-0379
VL - 7
JO - Research and Practice in Thrombosis and Haemostasis
JF - Research and Practice in Thrombosis and Haemostasis
IS - 3
M1 - 100128
ER -
