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

Lisa Clarke; Timothy Brighton; Sanjeev D Chunilal; Christine S M Lee; Freda Passam; Jennifer Curnow; Vivien M Chen; Huyen A Tran

doi:10.1016/j.vaccine.2023.03.071

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.

Authors

Lisa Clarke¹, Timothy Brighton², Sanjeev D Chunilal³, Christine S M Lee⁴, Freda Passam⁵, Jennifer Curnow⁶, Vivien M Chen⁷, Huyen A Tran⁸

Affiliations

¹ Transfusion Policy and Education, Australian Red Cross Lifeblood, Sydney, NSW, Australia; Department of Haematology, Concord Repatriation General Hospital, NSW Health Pathology, Sydney, NSW, Australia. Electronic address: Lclarke@redcrossblood.org.au.
² Department of Haematology, Prince of Wales Hospital, Randwick, New South Wales Health Pathology, Sydney, NSW, Australia.
³ Department of Clinical Haematology, Monash Medical Centre, Melbourne, Victoria, Australia.
⁴ ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia.
⁵ Department of Haematology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
⁶ Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Department of Haematology, Westmead Hospital, Sydney, NSW, Australia.
⁷ Department of Haematology, Concord Repatriation General Hospital, NSW Health Pathology, Sydney, NSW, Australia; ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
⁸ Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australia; Department of Clinical Haematology, The Alfred Hospital, Melbourne, Victoria Australia.

PMID: 37085453
DOI: 10.1016/j.vaccine.2023.03.071

Abstract

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
Chromosome Breakage
Chromosome Disorders
Female
Humans
Male
Purpura, Thrombocytopenic, Idiopathic* / chemically induced
Thrombocytopenia* / chemically induced
Thrombocytopenia* / congenital
Thrombosis*
Vaccination / adverse effects
Vaccines

Substances

Antibodies
ChAdOx1 nCoV-19
Vaccines
COVID-19 Vaccines

Supplementary concepts

Thrombocytopenia chromosome breakage