(SLC-053) Risk of Venous Thrombosis With Thrombocytopenia Syndrome After Vaccination With AZD1222: A European VAC4EU Post-Authorisation Safety Study

Tuesday, August 26, 2025

12:15 PM - 1:15 PM ET

Co-Author(s)

Joan Forns, MPH, PhD

Director, Epidemiology
Pharmacoepidemiology and Risk Management, RTI Health Solutions, Barcelona, Spain
RP

Romin Pajouheshnia

Pharmacoepidemiology and Risk Management, RTI Health Solutions, Barcelona, Netherlands
TA

Taylor Aurelius

Drug Safety Research Unit (DSRU), Southampton, UK, United Kingdom
ZB

Zachary Bouck

Safety Epidemiology, Chief Medical Office, R&D, AstraZeneca, Mississauga, Canada, Canada
JC

Juan José Carreras Martínez

Vaccine Research Department, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO-Public Health), Valencia, Spain, Spain
JC

Jungyeon Choi

Department of Data Science and Biostatistics, Julius Center for Health Science and Primary Care, University Medical Center of Utrecht, Utrecht University, Utrecht, The Netherlands, Netherlands
AC

Albert Cid Royo

Department of Data Science and Biostatistics, Julius Center for Health Science and Primary Care, University Medical Center of Utrecht, Utrecht University, Utrecht, The Netherlands, Netherlands
EC

Elisa Correcher Martínez

Vaccine Research Department, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO-Public Health), Valencia, Spain, Spain
SF

Silvia Fernandez-Garcia, MD

Fundació Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
Barcelona, Catalonia, Spain
CF

Catherine Fry

Drug Safety Research Unit, Southampton, UK, United Kingdom
JG

Jordy Gaspersz

PHARMO Institute for Drug Outcomes Research, Utrecht, The Netherlands, Netherlands
MG

Maria Giner-Soriano, PharmD, PhD

Researcher
Fundació Institut Universitari per a la Recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
Barcelona, Catalonia, Spain
Rosa Gini, PhD

Agenzia Regionale di Sanità della Toscana (ARS Toscana), Florence, Italy, Italy
AG

Anna Girardi

Agenzia Regionale di Sanità della Toscana (ARS Toscana), Florence, Italy, Italy
RH

Ron Herings

PHARMO Institute for Drug Outcomes Research, Utrecht, The Netherlands, Netherlands
WH

Wan-Ting Huang

National Taiwan University Children’s Hospital, Taipei, Taiwan, Taiwan (Republic of China)
GH

Giulia Hyeraci

Agenzia Regionale di Sanità della Toscana (ARS Toscana), Florence, Italy, Italy
JK

Joseph Kim, PhD

Head, Safety Epidemiology
Safety Epidemiology, Chief Medical Office, R&D, AstraZeneca, Cambridge, UK, United Kingdom
SL

Samantha Lane

Drug Safety Research Unit, Southampton, UK, United Kingdom
DL

Deborah Layton, FISPE FRPharmS PhD

Principal and Drug Safety Lead, Health Analytics
Lane Clark & Peacock (LCP) LLP , UK
Winchester, England, United Kingdom
AL

Andrew Lee

BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK, United Kingdom
TL

Thom Lysen

PHARMO Institute for Drug Outcomes Research, Utrecht, The Netherlands, Netherlands
DM

David Martinez

Pharmacoepidemiology and Risk Management, RTI Health Solutions, Barcelona, Spain, Spain
DM

Denise Morris

Drug Safety Research Unit, Southampton, UK, United Kingdom
RM

Rosa Morros, MD, PhD

Fundació Institut Universitari per a la Recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain, Spain
DO

Dan Ouchi

Fundació Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain, Spain
JO

Jetty Overbeek

PHARMO Institute for Drug Outcomes Research, Utrecht, The Netherlands, Netherlands
Susana Perez-Gutthann, MD, PhD, FISPE, FRCP

Sn VP, Regulatory RWE/Epidemiology & Biostatistics
Pharmacoepidemiology and Risk Management, RTI Health Solutions, Barcelona, Spain
Barcelona, Catalonia, Spain
Estel Plana, MSc

Director Biostatistician
Pharmacoepidemiology and Risk Management, RTI Health Solutions, Barcelona, Spain, Spain
RP

Robert W. Platt, PhD

Principal Investigator
Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada, Quebec, Canada
GR

Giuseppe Roberto

Agenzia Regionale di Sanità della Toscana (ARS Toscana), Florence, Italy, Italy
DR

Debabrata Roy

Drug Safety Research Unit (DSRU), Southampton, UK, United Kingdom
MS

Miriam C.J. Sturkenboom

Department of Data Science and Biostatistics, Julius Center for Health Science and Primary Care, University Medical Center of Utrecht, Utrecht University, Utrecht, The Netherlands, Netherlands
HU

Hae-Won Uh

Department of Data Science and Biostatistics, Julius Center for Health Science and Primary Care, University Medical Center of Utrecht, Utrecht University, Utrecht, The Netherlands, Netherlands
AU

Arantxa Urchueguía

Vaccine Research Department, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO-Public Health), Valencia, Spain, Spain
DW

Daniel Weibel

Vaccine monitoring collaboration for Europe (VAC4EU), Brussels, Belgium, Netherlands

Presenting Author(s)

CR

Cristina Rebordosa, MD, PhD

Senior Director Epidemiology
Pharmacoepidemiology and Risk Management, RTI Health Solutions, Barcelona, Spain, Catalonia, Spain

Background: AstraZeneca was asked to conduct a post-authorisation safety study (PASS) for the AZD1222 COVID-19 vaccine. One of the 40 PASS outcomes was thrombosis with thrombocytopenia syndrome (TTS) for which a signal was detected in March 2021 and additional risk minimisation measures (RMM) were implemented, including age restrictions.

Objectives: To estimate the risk of TTS in subjects who received ≥1 dose of AZD1222, compared to concurrent unvaccinated subjects (primary), pre-pandemic historical comparators, or mRNA-vaccinated subjects (exploratory).

Methods: A cohort study was conducted using secondary data—CPRD (UK), VID (Valencia, Spain), SIDIAP (Catalonia, Spain), and PHARMO (The Netherlands). AZD1222-vaccinated subjects were 1:1 matched on age, sex, region, prior COVID-19, and by special populations of interest. As no TTS code exists, venous TTS (42-day risk window) was defined as a thromboembolic event (TE) and thrombocytopenia (TCP) ±10 days, and no TTS in the last year, with prior TE/TCP permitted. Incidence rates (IR) per 10,000 py and IR ratios (IRR) were estimated using propensity score-weighted Poisson regression. Subgroup, sensitivity, and meta-analyses were performed. Instead of a dichotomous interpretation based on significance testing, our interpretation considers the magnitude, precision, and potential bias.

Results: 5,321,930 AZD1222-vaccinated subjects were matched to concurrent unvaccinated subjects, 4,831,010 to historical comparators (CPRD, SIDIAP, PHARMO), and 4,028,091 to mRNA-active comparators (CPRD). In CPRD, 83% of subjects were vaccinated in Q1 2021 (pre-RMM implementation), and 64% were < 60 yrs. In VID, SIDIAP, and PHARMO, >60% were vaccinated after Q1 2021; most subjects were aged ≥60 yrs.
In the primary analysis, IRR (95% CIs) for TTS were 1.14 (0.60-2.17) in CPRD, 0.34 (0.10-1.18) in VID, and 0.66 (0.33-1.34) in SIDIAP; PHARMO identified no TTS events. Estimated IR and IRR for TTS, where available, were higher in the AZD1222 cohort than in the concurrent unvaccinated cohort in people aged < 60 yrs or when using shorter risk windows. After case validation, PPV-adjusted IRRs were below 1 in all data sources.
In the historical comparators analysis, meta-analysis yielded an IRR of 1.78 (1.12-2.82; I2=0%). In the mRNA-active comparators analysis, the IRR was 1.12 (0.61-2.05).

Conclusions: Acknowledging limitations introducing uncertainty, such as potential outcome misclassification, the totality of evidence suggests a possible increased risk of TTS post-AZD1222 vaccination that may be higher among individuals aged < 60 yrs, which is in line with the literature. Differential age distributions, resulting from country-level differences in the RMMs, may explain IRR disparities across data sources.