Risk of Vaccine-Induced Thrombotic Thrombocytopenia (VITT) following the AstraZeneca/COVISHIELD Adenovirus Vector COVID-19 Vaccines

Key Message

Published estimates of the risk of vaccine-induced thrombotic thrombocytopenia (VITT) from countries with moderate to high data quality range from 1 case per 26,500 to 1 case per 127,300 first doses of AstraZeneca/COVISHIELD administered (Table 1).

The risk of VITT in Canada as of May 8, 2021 has been estimated to be approximately 1 per 55,000 doses, but several presumptive cases are still under investigation.

Country	Cases	Estimated Persons Receiving 1 undefinedst Dose of Vaccine	Incidence	Data Quality	Peer Reviewed	Case Ascertainment and Estimation of Denominator Population
Norway 1	5	132,686	1:26,500	High	Yes	Centralized electronic health record system used to ascertain cases. Vaccination paused after cases discovered allowing accurate estimation of the denominator population at risk of VITT.
Netherlands 2	8	400,000	1:50,000	Uncertain	No	Unclear.
Canada 5,12	-	-	1:55,000	Uncertain	No	Retrospective ascertainment of cases since April 2021, frequency of cases may therefore be underestimated. Vaccination ongoing, size of the denominator population therefore overestimated.
Denmark 3	2	148,792	1:74,400	High	No	Centralized electronic health record system used to ascertain cases. Vaccination paused after cases discovered allowing accurate estimation of the denominator population at risk of VITT.
UK 4	242	22,600,000	1:93,400	Moderate	No	Ambispective pharmacovigilance for thrombotic events after vaccination, frequency of cases may therefore be underestimated initially. Vaccination ongoing, size of the denominator population therefore overestimated.
Germany 6	21	2,270,000	1:108,100	Uncertain	No	Unclear.
France 7	23	2,725,089	1:118,500	Moderate	No	Ambispective pharmacovigilance for thrombotic events after vaccination, frequency of cases may therefore be underestimated initially. Vaccination ongoing and no distinction made between first and second doses, size of the denominator population therefore overestimated.
Australia 8	11	1,400,000	1:127,300	Moderate	No	Ambispective pharmacovigilance for thrombotic events after vaccination, frequency of cases may therefore be underestimated initially. Vaccination ongoing and no distinction made between first and second doses, size of the denominator population therefore overestimated.
Italy 9	11	1,630,000	1:148,200	Uncertain	No	Unclear.

Background

The AstraZeneca/COVISHIELD COVID-19 vaccine is associated with immune thrombosis that is similar to heparin-induced thrombocytopenia (HIT).¹¹ Affected individuals have antibodies targeted against platelet factor 4 (PF4) that presumably induce massive platelet activation, reducing the platelet count and causing thrombosis. It has been referred to as VITT. To date, reported cases of VITT occurred between 4 and 28 days after administration of the AstraZeneca/COVISHIELD COVID-19 vaccine.¹¹

Questions

What is the reported risk of VITT following the first dose of the AstraZeneca/COVISHIELD COVID-19 vaccine in different countries?

Findings

Published estimates of the risk of VITT from countries with moderate to high data quality range from 1 case per 26,500¹ to 1 case per 127,300⁸ first doses of AstraZeneca/COVISHIELD administered (Table 1). Countries with higher data quality tend to show higher estimates of the risk of VITT.

The quality of the data varies among countries and depends on the accuracy of case ascertainment (the number of reported VITT cases used as numerator) and the reliability of the estimated size of the vaccinated population (denominator population who received the first dose of the vaccine and was at risk of VITT). The numerator in this ratio is more difficult to ascertain with certainty due to underdiagnosis.

The risk of VITT in Canada as of May 8, 2021 has been estimated to be approximately 1 per 55,000 first doses.^5,12

Interpretation

Published estimates of the risk of VITT currently range from 1 case per 26,500 to 1 case per 127,300 first doses of AstraZeneca/COVISHIELD administered. The risk of VITT in Canada has been estimated to be approximately 1 per 55,000 first doses, but several possible cases are still under investigation. Early data from the United Kingdom suggests that the risk of VITT after second doses of AstraZeneca/COVISHIELD vaccines is likely lower than after first doses.⁴

Methods Used in This Science Brief

We examined data up until May 8, 2021 from countries which have publicly reported VITT cases and had estimates of numbers of prior vaccinations with AstraZeneca/COVISHIELD COVID-19 vaccines. We excluded countries which had not yet approved the vaccine, elected to not use it, had not publicly reported data within the study period, or had reported some cases but no reported vaccination counts.¹³

We examined information from regulatory authorities, press releases, scientific journals, and media reports. We included only reports of VITT cases with thrombosis associated with thrombocytopenia after vaccination. Cases with only clotting (i.e., arterial or venous thrombosis) and no documented thrombocytopenia were excluded. To estimate the risk of VITT, we matched the announcement date of cases to the number of vaccinations given approximately two weeks prior to the date.¹³

Data were considered to be of high quality (1) if there was reliable case ascertainment, typically enabled by a universal electronic health record system, and (2) if the denominator population at risk of developing VITT 4 to 28 days after vaccination could be reliably estimated, for example if countries had paused vaccination after reports of thrombotic events. Data were considered to be of moderate quality if (1) there was dedicated pharmacovigilance undertaken to identify cases, which was prospective or ambispective (including both a retrospective and prospective element), and (2) the denominator population at risk of developing VITT 4 to 28 days after vaccination could not be reliably estimated. Data were considered to be of uncertain quality if case ascertainment was unclear or only performed retrospectively.