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Editorials
A new enemy is emerging in the fight against the SARS-CoV-2 pandemic
Francesco Rodeghiero1 and Carlo L. Balduini2
1Hematology Project Foundation, Vicenza and 2Fondazione Ferrata-Storti, Pavia, Italy E-mail: CARLO L. BALDUINI - carlo.balduini@unipv.it
doi:10.3324/haematol.2021.279186
The discovery of a new disease is always big news even more so when a new iatrogenic disorder emerges after the administration of a vaccine to millions of people during a global pandemic. This is pre- cisely the case of vaccine-induced immune thrombotic thrombocytopenia (VITT) reported after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). VITT was first described in April 2021 by three independent groups in 39 people, 5 to 29 days after the first administration of the vaccine ChAdOx1 nCoV- 19 (AstraZeneca), a recombinant chimpanzee adenoviral vector encoding the spike protein of SARS-CoV-2.1-3 Affected people were young or middle-aged adults, most- ly women, who had acute onset of moderate to severe thrombocytopenia and thrombosis, often in unusual localizations such as cerebral venous sinus or portal, splanchnic, or hepatic veins. Other patients presented with venous thromboembolisms or acute arterial throm- bosis. The disease was serious, with 40% mortality. Of note, nearly all patients had high levels of antibodies reacting to platelet factor 4 (PF4)-heparin complexes, as in heparin-induced thrombocytopenia, but they had not been previously exposed to this anticoagulant. This find- ing suggests a close correlation between VITT and autoimmune heparin-induced thrombocytopenia, which occurs in patients never exposed to heparin. The sequence of events leading to thrombosis did not emerge from these three pioneering studies. In particular, the nature of the polyanion macromolecule mimicking heparin remains uncertain. While the intact vaccine did not seem to be implicated, a pathogenic role of some spe-
cific components, including the spike protein synthetized by the vaccine, could not be ruled out.
In this issue of Haematologica, two papers provide new information on VITT. The article by Althaus et al.4 describes the clinical and laboratory features of eight additional cases and significantly confirms the clinical and laboratory picture that has emerged from previous reports. Furthermore, this study provides new evidence of the pathogenesis of VITT by comparison of platelet activation induced by sera from patients with this condi- tion with sera from subjects vaccinated without any clin- ical complications, as well as from patients with SARS- CoV-2. Finally, the authors report on the autopsy findings of two deceased VITT patients that revealed multidistrict thrombosis and showed kidney lesions similar to those of thrombotic microangiopathies.
The letter by Pomara et al.5 published in the same issue focuses on the results of a thorough post-mortem examina- tion of two patients with typical VITT. The macroscopic picture was impressive revealing the extent of thrombosis which was much more widespread than initially revealed by imagining during life. The authors made extensive use of immunocytochemistry for the characterization of the affected organs and noted, among other interesting find- ings, platelet aggregates diffusely lining the endothelial layer of small and medium vessels. Pomara’s paper, there- fore, confirms the observation made by Althaus that VITT has this feature in common with thrombotic microangiopathies, confirming that generalized platelet activation plays a major role in this disorder.
The study of these additional ten new cases advances
Figure 1. Of the 49 patients with vaccine-induced immune thrombotic thrombocytopenia reported to date, 79% were women and only 4% were over 60 years old.
The risk of this disease, therefore, seems to be extremely low in old people who, on the other hand, have a high risk of death from SARS-CoV-2. The administration of adenoviral vaccines against SARS-CoV-2 is therefore highly advantageous in this category of subjects. Conversely, vaccine-induced immune thrombotic thrombo- cytopenia (VITT) seems to be more common in young or middle-aged adults, especially women, who instead have a risk of death from SARS-CoV-2 much lower and in some age categories even close to zero. Pending new data, these considerations have convinced some countries not to administer adenoviral vaccines to young subjects.
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haematologica | 2021; 106(8)