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

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:

viral vector COVID-19 vaccines (column labelled viral vector):
- AstraZeneca Vaxzevria
- AstraZeneca and Verity/SII COVISHIELD
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:

they did not meet the case definition of TTS (n=11) or
there was insufficient information provided to conduct a causality assessment (n=8)

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

Janssen Jcovden (Johnson & Johnson)
Novavax Nuvaxovid

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 event^{table 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 certainty^{table 1 note 2}
Level 1	50	24	74
Level 2 or 3	3	7	10
WHO AEFI classification^{table 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 location^{table 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 thrombosis^{table 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 one^{table 2 note 1}	34
Anti-PF4 antibody testing
Functionally positive	37
Brighton Collaboration case definition level of certainty^{table 2 note 2}^{table 2 note 3}
Level 1	37
Clot location^{table 2 note 4}
Pulmonary embolism	16
Cerebral venous thrombosis (includes cerebral venous sinus thrombosis)	10
Deep vein thrombosis	8
Venous thrombosis, other	9
Arterial thrombosis^{table 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

Page details

Date modified:: 2023-01-11

Language selection

Search

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

On this page