Vaccine-induced immune thrombotic thrombocytopenia post dose 2 ChAdOx1 nCoV19 vaccination: Less severe but remains a problem

Vaccine. 2023 May 11;41(20):3285-3291. doi: 10.1016/j.vaccine.2023.03.071. Epub 2023 Apr 19.


Background: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but established complication of 1st dose ChAdOx1 nCoV19 vaccination (AZD1222), however this complication after dose 2 remains controversial.

Objectives: To describe the clinicopathological features of confirmed cases of VITT post dose 2 AZD1222 vaccination in Australia, and to compare this cohort to confirmed cases of VITT post 1st dose.

Methods: Sequential cases of clinically suspected VITT (thrombocytopenia, D-Dimer > 5x upper limit normal and thrombosis) within 4-42 days of dose 2 AZD1222 referred to Australia's centralised testing centre underwent platelet activation confirmatory testing in keeping with the national diagnostic algorithm. Final classification was assigned after adjudication by an expert advisory committee. Descriptive statistics were performed on this cohort and comparative analyses carried out on confirmed cases of VITT after 1st and 2nd dose AZD1222.

Results: Of 62 patients referred, 15 demonstrated presence of antibody mediated platelet activation consistent with VITT after dose 2 AZD1222. Four were immunoassay positive. Median time to presentation was 13 days (range 1-53) platelet count 116x10^9/L (range 63-139) and D-dimer elevation 14.5xULN (IQR 11, 26). Two fatalities occurred. In each, the dosing interval was less than 30 days. In comparison to 1st dose, dose 2 cases were more likely to be male (OR 4.6, 95% CI 1.3-15.8, p = 0.03), present with higher platelet counts (p = 0.05), lower D-Dimer (p = 01) and less likely to have unusual site thromboses (OR 0.14, 95% CI 0.04-0.28, p = 0.02).

Conclusions: VITT is a complication of dose 2 AZD1222 vaccination. Whilst clinicopathological features are less severe, fatalities occurred in patients with concomitant factors.

Keywords: ChAdOx1 nCoV19 vaccination; Dose 2; Thrombosis with thrombocytopenia syndrome; VITT; Vaccine-induced immune thrombotic thrombocytopenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies
  • COVID-19 Vaccines* / adverse effects
  • ChAdOx1 nCoV-19
  • Female
  • Humans
  • Male
  • Purpura, Thrombocytopenic, Idiopathic* / chemically induced
  • Thrombocytopenia* / chemically induced
  • Thrombosis*
  • Vaccination / adverse effects
  • Vaccines


  • Antibodies
  • ChAdOx1 nCoV-19
  • Vaccines
  • COVID-19 Vaccines

Supplementary concepts

  • Thrombocytopenia chromosome breakage