Content area
Full text
Introduction
Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a new clinical entity first described after the administration of adenovirus-vectored COVID-19 vaccines including Ad26.COV2.S (Janssen, referred to hereafter as Ad26) and ChAdOx1 nCoV-19 (AstraZeneca, referred to hereafter as ChAdOx1), VITT is characterised by the onset of symptoms 5–30 days after COVID-19 vaccination, with thrombocytopenia, thrombosis, presence of anti-platelet factor 4 (PF4) antibodies, and grossly elevated D-dimer1. Thromboses frequently occur in multiple vascular beds and unusual anatomical sites such as the cerebral venous sinuses, internal jugular and splanchnic veins. Case identification is challenged by the rarity of the disease, lack of awareness, diverse clinical presentations due to varied loci of thromboses, variable access to laboratory investigations, and confusion with thrombotic thrombocytopenic syndromes identified after vaccination that may or may not be causally related2, 3, 4, 5–6. As a result, the true incidence of VITT is difficult to establish. Incidence rates of VITT appear to be higher after ChAdOx1 than Ad267,8, a phenomenon potentially contributed to by differences in process-related impurities, with higher levels of anti-PF4 complexes and increased vascular permeability observed after ChAdOx than Ad269. However, accurate comparison of incidence is not possible due to differences in the way each vaccine was deployed in terms of geographical distribution, age and risk groups targeted for vaccination, and disease awareness. Incidence rates have been reported to be highest in women aged 30–49 years1,7,10, but sex-specific exposure data for each vaccine to guide interpretation of this observation are limited.
The differential diagnosis of VITT includes other immune-mediated causes of thrombosis with co-occurring thrombocytopenia, such as heparin-induced thrombocytopenia (HIT), antiphospholipid syndrome, and haemolytic-uraemic syndrome, as well as non-immune mediated causes, such as malignancies, liver disease, septicaemia, haemolysis-elevated liver enzymes and low platelets syndrome and drug toxicity. Co-occurring thrombosis and thrombocytopenia may also be associated with infections, such as dengue or cerebral malaria11.
There is increasing understanding of the underlying pathophysiological processes of VITT, the nature of the VITT anti-PF4 antibodies and the immune-complex activation of platelets and leucocytes12, 13–14. Large scale epidemiological studies have not shown increased thrombosis with mRNA vaccines and VITT has not been reported after vaccination with other Ad26-vector vaccines that have been...