Thrombosis and thrombocytopenia after vaccination against and infection with SARS-CoV-2 in the United Kingdom

Abstract

Population-based studies can provide important evidence on the safety of COVID-19 vaccines. Using data from the United Kingdom, here we compare observed rates of thrombosis and thrombocytopenia following vaccination against SARS-CoV-2 and infection with SARS-CoV-2 with background (expected) rates in the general population. First and second dose cohorts for ChAdOx1 or BNT162b2 between 8 December 2020 and 2 May 2021 in the United Kingdom were identified. A further cohort consisted of people with no prior COVID-19 vaccination who were infected with SARS-Cov-2 identified by a first positive PCR test between 1 September 2020 and 2 May 2021. The fourth general population cohort for background rates included those people in the database as of 1 January 2017. In total, we included 3,768,517 ChAdOx1 and 1,832,841 BNT162b2 vaccinees, 401,691 people infected with SARS-CoV-2, and 9,414,403 people from the general population. An increased risk of venous thromboembolism was seen after first dose of ChAdOx1 (standardized incidence ratio: 1.12 [95% CI: 1.05 to 1.20]), BNT162b2 (1.12 [1.03 to 1.21]), and positive PCR test (7.27 [6.86 to 7.72]). Rates of cerebral venous sinus thrombosis were higher than otherwise expected after first dose of ChAdOx1 (4.14 [2.54 to 6.76]) and a SARS-CoV-2 PCR positive test (3.74 [1.56 to 8.98]). Rates of arterial thromboembolism after vaccination were no higher than expected but were increased after a SARS-CoV-2 PCR positive test (1.39 [1.21 to 1.61]). Rates of venous thromboembolism with thrombocytopenia were higher than expected after a SARS-CoV-2 PCR positive test (5.76 [3.19 to 10.40]).

Head-to-head comparison of four COVID-19 vaccines on platelet activation, coagulation and inflammation. The TREASURE study

“…However, limited post-vaccination increments in D-dimer and F 1 +2 , along with endothelial stunning may become significant, albeit weakly, at a population level. A pivotal paper published online in November 2022 [33] reported minor, but statistically significant, 12 % and 25 % higher risks of venous thromboembolism and pulmonary embolism, respectively, following the first dose of either Comirnaty or Vaxzevria compared to the general population. Corresponding risks observed following SARS-Cov-2 infection from September 1st 2020 up to May 2nd 2021 were respectively 61-fold and 49-fold higher; nonetheless, our findings may at least partially explain the rare occurrence of venous thromboembolic complications in subjects with hyper-inflammatory reactions to vaccination.…”

New‐onset and relapsed thrombotic microangiopathy post‐COVID‐19 vaccination

“…As per the previous evidence, most adverse events following vaccination were nonserious, such as fatigue, headache, and myalgia 3 . Although rare, vaccine‐induced thrombotic complications have recently attracted extensive concern 4,5 …”

“…3 Although rare, vaccine-induced thrombotic complications have recently attracted extensive concern. 4,5 Thrombotic microangiopathy (TMA), a pathological manifestation observed in multiple diseases, is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and ischemic organ damage. 6,7 Thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome (aHUS) are significant subtypes of TMA.…”

An international survey of venous thromboembolic events and current practices of peri‐operative VTE prophylaxis after living donor hepatectomy

“…21 This issue has been compounded by the COVID-19 pandemic as there is evidence of increased VTE events after COVID infection. 22 This may be of particular relevance to potential donors with recent symptomatic or asymptomatic COVID-19 infection.…”

“…— 20 Studies have shown that LDH may be associated with a pro‐coagulant profile in the early post‐operative period which could potentially increase VTE risk 21 . This issue has been compounded by the COVID‐19 pandemic as there is evidence of increased VTE events after COVID infection 22 . This may be of particular relevance to potential donors with recent symptomatic or asymptomatic COVID‐19 infection.…”