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Antibodies to Platelet Factor 4 are Associated with COVID-19 Vaccine-Induced Immune Thrombotic Thrombocytopenia

April 21, 2021

In the fight against SARS-CoV-2, many highly effective vaccines have been rapidly developed with different vectors and spike (S) protein inserts.  More than 400 million people have been vaccinated, and a few reports of serious adverse events have been reported.  At least three independent studies, however, have found that vaccination with ChAdOx1 nCoV-19 (AstraZeneca SARS-CoV-2 vaccine) can cause thrombocytopenia and thrombosis approximately 5 to 24 days after receiving the first of two doses.  The papers highlight 39 cases of a new syndrome coined vaccine-induced immune thrombotic thrombocytopenia (VITT), mainly in women younger than 50 years old with a case-fatality rate of approximately 40%.  Although the mechanism of pathogenesis is not clear, almost every patient had high levels of antibodies to platelet-factor 4, similar to heparin-induced thrombocytopenia (HIT) but without heparin exposure.  The vaccine has now been given to over 34 million people.  European agencies report about 160 other cases of possible VITT with the AstraZeneca vaccine.  In addition, at least 20 cases of thrombocytopenia have been reported following the Pfizer and Moderna mRNA vaccines.  Further surveillance and investigations into the mechanism(s) of these thrombotic and thrombocytopenic events are needed.  However, it will be important for clinical pathology laboratories to be prepared to provide platelet-factor 4 antibody testing and apheresis treatments if the patients do not respond to steroids and intravenous immunoglobulin.

References:

  1. Cines DB and J.B. Bussel. SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia.  The New England Journal of Medicine 2021
  2. Greinacher A, Thiele T, Warkentin TE, Weisser K, et al. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination.  The New England Journal of Medicine 2021
  3. Schultz NH, Sørvoll IH, Michelesen AE, et al. Thrombosis and thrombocytopenia after ChAdOx1 nCov-19 vaccination.  The New England Journal of Medicine 2021
  4. Scully M, Singh D, Lown R, Poles A, et al. Pathologic antibodies to platelet factor 4 after ChAdOx1 nCov-19 vaccination.  The New England Journal of Medicine 2021
  5. Lee EJ, Cines DB, Gernsheimer T, Kessler C, et al. Thrombocytopenia following Pfizer and Moderna SARS-CoV-2 vaccination.  Am J Hematol 2021; 96;534-537

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