Management of cerebral and splanchnic vein thrombosis associated with thrombocytopenia in subjects previously vaccinated with Vaxzevria (AstraZeneca): a position statement from the Italian Society for the Study of Haemostasis and Thrombosis (SISET).

Correspondence: Valerio De Stefano e-mail: valerio.destefano@unicatt.it 1Department of Medicine and Surgery, Section of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy; 2Department of Oncology and Haematology, University Hospital, Modena, Italy; 3Department of Medicine and Surgery, “Insubria” University, Varese, Italy; 4Department of Experimental and Clinical Medicine, “Careggi” University Hospital, University of Florence, Florence, Italy; 5“A.O. SS. Antonio e Biagio” Hospital, Alessandria, Italy; 6Department of Medicine and Surgery, Research Centre on Thromboembolic Disorders and Antithrombotic Therapies, University of Insubria, Varese, Italy; 7Department of Immunohaematology and Transfusion Medicine, “Papa Giovanni XXIII” Hospital, Bergamo; 8Thrombosis and Haemostasis Unit, Fondazione I.R.C.C.S. “Casa Sollievo della Sof ferenza”, S. Giovanni Rotondo, Foggia, Italy; 9“Arianna Anticoagulazione” Foundation, Bologna, Italy; 10Fondazione IRCCS “Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi” Haemophilia and Thrombosis Centre and “Fondazione Luigi Villa”, Milan, Italy; 11Section of Haematology, Department of Radiological and Haematological Sciences, Catholic University, Fondazione Policlinico “A. Gemelli” IRCCS, Rome, Italy ChAdOx1 nCOV-19 (Vaxzevria) is a vaccine against SARS-CoV-2 infection (COVID-19) developed by Oxford University and AstraZeneca that uses a replication-deficient chimpanzee adenoviral vector (ChAdOx1) containing the SARS-CoV-2 structural surface glycoprotein antigen (spike protein; nCoV-19) gene1. Over the last few weeks, there have been several reports of thromboembolic events in subjects who had been administered Vaxzevria in the previous weeks. This led several European countries to decide to suspend its administration or, more recently, to limit it to subjects over 60 years of age2,3. While the incidence of venous thromboembolism (VTE) at usual sites in vaccinated subjects has not exceeded that in the non-vaccinated population4,5, a rare and particular type of event has been described following vaccination. This is characterised by cerebral and/or splanchnic vein thrombosis, often associated with multiple thromboses, with thrombocytopenia and bleeding, and sometimes disseminated intravascular coagulation (DIC), occurring in otherwise healthy subjects. This syndrome was mainly observed in females under 55 years of age, and the events occurred between 4 and 16 days after receiving the Vaxzevria vaccine, with a high fatality rate. It is known that it may be extremely difficult to prove that an adverse event following immunisation is actually caused by the vaccine itself when its occurrence is extremely rare6. However, the described clinical picture requires attention and it is emerging as a likely, although very rare, complication of vaccination with Vaxzevria7. Several scientific societies and experts have concluded for a causative role of Vaxzevria vaccination in these peculiar thrombotic events and two groups of investigators independently described this condition as a prothrombotic disorder resembling heparin-induced thrombocytopenia8,9 issuing a number of recommendations for its management10-12. However, some other cases recently reported were tested for anti PF4/heparin antibodies and found negative (manuscript in preparation). While awaiting a conclusive demonstration of causation and a more complete understanding