Interactions of adenoviruses with platelets and coagulation and the vaccine-associated autoimmune thrombocytopenia thrombosis syndrome

The Covid-19 pandemic has heavily impacted global health and economy and vaccination remains the primary way of controlling the infection. During the ongoing vaccination campaign some unexpected thrombotic events have emerged in subjects who recently received the AstraZeneca Vaxzevria vaccine or the Johnson&Johnson (Janssen) vaccine, two adenovirus vector-based vaccines. Epidemiological studies confirm that the observed/expected rate of these unusual thromboses is abnormally increased, especially in women in the fertile age. The characteristics of this complication, with venous thromboses at unusual sites, most frequently cerebral vein sinus but also splanchnic, often multiple associated thromboses, thrombocytopenia, and sometimes disseminated intravascular coagulation, are unique and the time course and tumultuous evolution are suggestive of an acute immunological reaction, and indeed platelet-activating anti-PF4 antibodies have been detected in a large fraction of the affected patients. Several data suggest that adenoviruses may interact with platelets, the endothelium and the blood coagulation system. Here we review the interactions between adenoviral vectors and the haemostatic system of possible relevance for the vaccine associated thrombotic thrombocytopenia syndrome, we analyse systematically the clinical data on the reported thrombotic complications of adenovirus-based therapeutics and discuss all the current hypotheses on the mechanisms triggering this novel syndrome. Although considering current evidence the benefit of vaccination clearly outweighs the potential risks, it is of paramount importance to fully unravel the mechanisms leading to the vaccine associated thrombotic thrombocytopenia syndrome and to identify prognostic factors through further research.