First-dose ChAdOx1 and BNT162b2 COVID-19 vaccines and thrombocytopenic, thromboembolic and hemorrhagic events in Scotland

Abstract

Reports of ChAdOx1 vaccine–associated thrombocytopenia and vascular adverse events have led to some countries restricting its use. Using a national prospective cohort, we estimated associations between exposure to first-dose ChAdOx1 or BNT162b2 vaccination and hematological and vascular adverse events using a nested incident-matched case-control study and a confirmatory self-controlled case series (SCCS) analysis. An association was found between ChAdOx1 vaccination and idiopathic thrombocytopenic purpura (ITP) (0–27 d after vaccination; adjusted rate ratio (aRR) = 5.77, 95% confidence interval (CI), 2.41–13.83), with an estimated incidence of 1.13 (0.62–1.63) cases per 100,000 doses. An SCCS analysis confirmed that this was unlikely due to bias (RR = 1.98 (1.29–3.02)). There was also an increased risk for arterial thromboembolic events (aRR = 1.22, 1.12–1.34) 0–27 d after vaccination, with an SCCS RR of 0.97 (0.93–1.02). For hemorrhagic events 0–27 d after vaccination, the aRR was 1.48 (1.12–1.96), with an SCCS RR of 0.95 (0.82–1.11). A first dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events. The attenuation of effect found in the SCCS analysis means that there is the potential for overestimation of the reported results, which might indicate the presence of some residual confounding or confounding by indication. Public health authorities should inform their jurisdictions of these relatively small increased risks associated with ChAdOx1. No positive associations were seen between BNT162b2 and thrombocytopenic, thromboembolic and hemorrhagic events.

Targeting SARS-CoV-2-Platelet Interactions in COVID-19 and Vaccine-Related Thrombosis

“…They found that there was an excess (observedexpected) of 1.33 cases of non-immune thrombocytopenia per 100,000 people and 0.45 per 100,000 for immune thrombocytopenia. There was also evidence of a small increase in arterial thrombosis and haemorrhagic events but no increase in venous thromboembolic events (Simpson et al, 2021). Thus, it would appear that platelet activation in response to AZD1222 is a real but rare (around 1 in 100,000) event although it is not clear if this is due to a response to the Adenovirus vector or to the SARS-CoV-2 spike protein or even to a combination of the two.…”

COVID-19 vaccination and immune thrombocytopenia

“…Estimating the 'true effect' is hampered by the multiple challenges associated with the diagnosis of ITP and the low number of incident ITP events observed. Overall, the authors conclude there is no clear evidence of an association of ITP with the first dose of the BNT162b2 vaccine and there is a possible small increased risk of ITP with the ChAdOx1 vaccine 1 .…”

“…With all of its benefits, there also comes the potential for side effects, including autoimmune responses. In this issue of Nature Medicine, Simpson and colleagues implicate the AstraZeneca (ChAdOx1) vaccine, but not the Pfizer (BNT162b2) vaccine, in the development of immune thrombocytopenia (ITP) 1 . In interpreting such findings, it is important to consider not only the strengths and limitations of the study but also the wider clinical context and the balance of risks and benefits of vaccination.…”

“…These included analysis of diagnostic codes, together with documentation of ITP-directed therapy (such as corticosteroids or intravenous immunoglobulin), in addition to the absence of concurrent and/or subsequent diagnostic codes for other known etiologies of thrombocytopenia (e.g., malignancy, myelodysplastic syndrome or drug-induced thrombocytopenia) 8 . Simpson et al also attempted to verify the use of ITP-directed therapy but were limited in their access to hospital medication records 1 .…”

Covid-19: AstraZeneca vaccine linked with small risk of ITP, real world data show

“…The autoimmune bleeding disorder is characterised by a decrease in the number of platelets, which can cause minor bruising in some patients and excessive bleeding and long term illness in others. The authors of the study, published in Nature Medicine , stress that the condition is treatable and that the benefits of vaccination greatly outweigh the risks 1…”