Thrombosis with thrombocytopenia syndrome: Findings from the Advisory Committee on Causality Assessment

On this page

Thrombosis with thrombocytopenia syndrome

Thrombosis with thrombocytopenia syndrome (TTS) is a serious health condition involving blood clots (thrombosis) with low platelets (thrombocytopenia). When reports of TTS after vaccination with COVID-19 viral vector vaccines started to emerge in 2021, TTS became a priority for investigation in Canada and globally. The Public Health Agency of Canada and Health Canada continue to closely monitor Canadian and international reports of thrombosis with thrombocytopenia syndrome following vaccination.

Health Canada worked with companies to update the product information (product monograph) based on emerging evidence. Updates included information about these very rare events of blood clots associated with low levels of platelets following immunization:

For more information, please refer to the Janssen and AstraZeneca Vaxzevria/COVISHIELD COVID-19 vaccine public advisory.

Demographics for reviewed case reports

The Advisory Committee on Causality Assessment (ACCA) completed a causality assessment on case reports of TTS. These cases followed COVID-19 vaccinations and were reported to the Canadian Adverse Events Following Immunization Surveillance System up to and including October 31, 2022.

In the following tables, all COVID-19 vaccines were the original formulations (no bivalent vaccines). For reporting in Table 1 and 2, the COVID-19 vaccines with case reports, were combined into 2 groups:

  1. viral vector COVID-19 vaccines (column labelled viral vector):
    • AstraZeneca Vaxzevria
    • AstraZeneca and Verity/SII COVISHIELD
  2. mRNA COVID-19 vaccines (column labelled mRNA):
    • Moderna Spikevax
    • Pfizer-BioNTech Comirnaty

A total of 103 cases were reported. Of those, 19 were excluded by ACCA because:

No cases of TTS were reported for the following COVID-19 vaccines distributed in Canada:

There were no cases reported for individuals under 30 years of age. Some rows have been combined to achieve a minimum count of 3 per cell.

The data on this page may change as ACCA receives more information about case reports.

Table 1. Demographics for case reports reviewed by ACCA of TTS reported up to and including October 31, 2022
Demographics Viral vector,
n=53
mRNA,
n=31
Total,
n=84
Age group (years)
Less than 50 20 5 25
50 and older 33 26 59
Sex
Female 25 8 33
Male 28 23 51
Dose number associated with eventtable 1 note 1
Dose number 1 50 19 69
Dose numbers 2 to 4 0 11 11
Anti-PF4 antibody testing
Functionally positive 37 0 37
Functionally negative 1 0 1
Screen negative, not tested or unknown 15 31 46
Brighton Collaboration case definition level of certaintytable 1 note 2
Level 1 50 24 74
Level 2 or 3 3 7 10
WHO AEFI classificationtable 1 note 3
A: Consistent with causal association to immunization A1: Vaccine product-related reaction (as per published literature) 37 0 37
B1: Indeterminate: Temporal relationship is consistent but there is insufficient definitive evidence for vaccine causing event (may be new vaccine-linked event) 0 12 12
B2: Indeterminate: Qualifying factors result in conflicting trends of consistency and inconsistency with causal association to immunization 8 0 8
C: Inconsistent with causal association to immunization: Coincidental underlying or emerging condition(s), or condition(s) caused by exposure to something other than vaccine 8 19 27
Clot locationtable 1 note 4
Pulmonary embolism 21 13 34
Cerebral venous thrombosis (includes cerebral venous sinus thrombosis) 11 0 11
Deep vein thrombosis 14 9 23
Venous thrombosis, other 12 4 16
Arterial thrombosistable 1 note 5 11 10 21
Outcome
Fatal 5 5 10

Definitions:
WHO: World Health Organization
AEFI: Adverse event following immunization

Table 1 Notes
Table 1 Note 1

Four cases did not report COVID-19 vaccine dose number associated with the reported event.

Return to table 1 note 1 referrer

Table 1 Note 2

Brighton Collaboration case definition Levels of Certainty shown in this table are limited to:

  • Level 1 Definite case
  • Level 2 Probable case
  • Level 3 Possible case

Return to table 1 note 2 referrer

Table 1 Note 3

Only WHO AEFI classifications A to C, are shown in this table.

Return to table 1 note 3 referrer

Table 1 Note 4

Some case reports described more than 1 clot location, resulting in more clot locations than case reports.

Return to table 1 note 4 referrer

Table 1 Note 5

Arterial thrombosis can include different sites.

Return to table 1 note 5 referrer

Demographics for case reports classified as consistent with causal association to immunization

In the following table, ACCA reviewed the demographics for a subset of Table 1 for TTS cases. The demographics are for cases that were reported up to and including October 31, 2022. These cases have a WHO classification consistent with causal association to immunization (A A1). All case reports represent events following immunization with a viral vector COVID-19 vaccine. All events occurred between March 1, 2021, and May 31, 2021.

Table 2. Demographics for case reports of TTS reported up to and including October 31, 2022, with a WHO classification consistent with causal association to immunization (A A1)
Demographics WHO AEFI
Classification A A1,
n=37
Age group (years)
Less than 50 19
50 and older 18
Sex
Female 18
Male 19
Dose number associated with event
Dose number onetable 2 note 1 34
Anti-PF4 antibody testing
Functionally positive 37
Brighton Collaboration case definition level of certaintytable 2 note 2table 2 note 3
Level 1 37
Clot locationtable 2 note 4
Pulmonary embolism 16
Cerebral venous thrombosis (includes cerebral venous sinus thrombosis) 10
Deep vein thrombosis 8
Venous thrombosis, other 9
Arterial thrombosistable 2 note 5 9
Outcome
Fatal 4

Definitions:
WHO: World Health Organization
AEFI: Adverse event following immunization

Table 2 Notes
Table 2 Note 1

Three cases did not report COVID-19 vaccine dose number associated with the reported event.

Return to table 2 note 1 referrer

Table 2 Note 2

Brighton Collaboration case definition Levels of Certainty for TTS are:

  • Level 1 Definite case
  • Level 2 Probable case
  • Level 3 Possible case

Return to table 2 note 2 referrer

Table 2 Note 3

All cases with a WHO AEFI classification of A A1, had a Brighton Collaboration case definition Level of Certainty 1.

Return to table 2 note 3 referrer

Table 2 Note 4

Some case reports described more than 1 clot location, resulting in more clot locations than case reports.

Return to table 2 note 4 referrer

Table 2 Note 5

Arterial thrombosis can include different sites.

Return to table 2 note 5 referrer

Related links

Report a problem or mistake on this page
Please select all that apply:

Thank you for your help!

You will not receive a reply. For enquiries, contact us.

Date modified: