Case Series of Thrombosis with Thrombocytopenia Syndrome following COVID-19 vaccination—United States, December 2020–August 2021

Abstract

BackgroundThrombosis with thrombocytopenia syndrome (TTS) is a potentially life-threatening condition associated with adenoviral-vectored COVID-19 vaccination. TTS presents similarly to autoimmune heparin-induced thrombocytopenia. Twelve cases of cerebral venous sinus thrombosis following Janssen/Johnson & Johnson (Ad26.COV2.S) COVID-19 vaccination have been described.ObjectiveDescribe surveillance data and reporting rates of TTS cases following COVID-19 vaccination.DesignCase series.SettingUnited StatesPatientsCase-patients reported to the Vaccine Adverse Event Reporting System (VAERS) receiving COVID-19 vaccine from December 14, 2020 through August 31, 2021, with thrombocytopenia and thrombosis (excluding isolated ischemic stroke or myocardial infarction). If thrombosis was only in an extremity vein or pulmonary embolism, a positive enzyme-linked immunosorbent assay for anti-platelet factor 4 antibody was required.MeasurementsReporting rates (cases/million vaccine doses) and descriptive epidemiology.Results52 TTS cases were confirmed following Ad26.COV2.S (n=50) or mRNA-based COVID-19 (n=2) vaccination. TTS reporting rates were 3.55 per million (Ad26.COV2.S) and 0.0057 per million (mRNA-based COVID-19 vaccines). Median age of patients with TTS following Ad26.COV2.S vaccination was 43.5 years (range: 18–70); 70% were female. Both TTS cases following mRNA-based COVID-19 vaccination occurred in males aged >50 years. All cases following Ad26.COV2.S vaccination involved hospitalization including 32 (64%) with intensive care unit admission. Outcomes of hospitalizations following Ad26.COV2.S vaccination included death (12%), discharge to post-acute care (16%), and discharge home (72%).LimitationsUnder-reporting and incomplete case follow-up.ConclusionTTS is a rare but serious adverse event associated with Ad26.COV2.S vaccination. The different demographic characteristics of the two cases reported after mRNA-based COVID-19 vaccines and the much lower reporting rate suggest that these cases represent a background rate.Funding SourceCDC

Risk of venous thromboembolism after COVID‐19 vaccination

“…Due to the concern for VITT in younger women, 9 the results were also stratified by sex and age (+/−60 years) and by vaccine manufacturer and there was no statistically significantly elevated risk of VTE within any of these subgroups with Janssen or Moderna vaccines. We did however observe an elevated post‐vaccination VTE risk in women less than 60 with Pfizer (aHR 1.53, 95% CI 1.07–2.19) whereas men less than 60 had a lower risk of VTE (aHR 0.70, 95% CI 0.50–0.97).…”

“…A sensitivity analysis was also performed excluding any patients with documented COVID-19 infection and the results did not change significantly (Janssen: aHR 0.98, 95% CI 0.60-1.58; Moderna: aHR 0.91, 95% CI 0.77-1.07; Pfizer aHR 0.99, 95% CI 0.86-1.15). Due to the concern for VITT in younger women, 9 the results were also stratified by sex and age (+/−60 years) and by vaccine manufacturer and there was no statistically significantly elevated risk of VTE within any of these subgroups with Janssen or Moderna vaccines. We did however observe an elevated post-vaccination VTE risk in women less than 60 with Pfizer (aHR 1.53, 95% CI 1.07-2.19) whereas men less than 60 had a lower risk of VTE (aHR 0.70, 95% CI 0.50-0.97).…”

Phenotype Algorithms for the Identification and Characterization of Vaccine-Induced Thrombotic Thrombocytopenia in Real World Data: A Multinational Network Cohort Study

“…VITT cases reported after the adenovirus COVID-19 vaccines were likely to be healthy women of reproductive age [ 5 , 16 , 17 ]. Our data suggest that the patient profiles of the captured TWT cases (using any of the proposed phenotypes and across all data sources) are not consistent with such a profile.…”

“…Multiple conditions are associated with both thrombosis and thrombocytopenia, including heparin-induced thrombocytopenia (HIT), antiphospholipid syndrome, thrombotic thrombocytopenic purpura (TTP), disseminated intravascular coagulation (DIC), and some malignant tumors. However, the term VITT today (also termed thrombosis with thrombocytopenia syndrome [TTS]) [ 5 ] refers specifically to the syndrome associated with COVID-19 vaccines and is considered a new clinical syndrome. As such, there is currently no standard case definition for VITT accepted for use by all countries.…”

Comparative analysis of ChAdOx1 nCoV-19 and Ad26.COV2.S SARS-CoV-2 vector vaccines

“…The incidence rate of VITT/TTS seems to be higher for ChAdOx1 nCoV-19. The reported rate of VITT/TTS in the USA is 0.355 cases per 100,000 people vaccinated with Ad26.COV2.S, 3 compared to 1 per 50,000-100,000 people vaccinated with ChAdOx1 nCoV-19 in the UK. 4 In Germany both vaccines were used and within this medical system, 0.56 suspected cases per 100,000 vaccine doses for Ad26.COV2.S (3,186,297 vaccine doses administered) and 1.49 suspected cases per 100,000 vaccine doses for ChAdOx1 nCoV-19 (12,692,700 vaccine doses administered) were reported.…”