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Globally, at the time of writing (20 March 2021), 121.759.109 confirmed COVID-19 cases have been reported to the WHO, including 2.690.731 deaths. Globally, on 18 March 2021, a total of 364.184.603 vaccine doses have been administered. In Italy, 3.306.711 confirmed COVID-19 cases with 103.855 deaths have been reported to WHO. In Italy, on 9 March 2021, a total of 6.634.450 vaccine doses have been administered. On 15 March 2021, Italian Medicines Agency (AIFA) decided to temporarily suspend the use of the AstraZeneca COVID-19 vaccine throughout the country as a precaution, pending the rulings of the European Medicines Agency (EMA). This decision was taken in line with similar measures adopted by other European countries due to the death of vaccinated people. On 18 March 2021, EMA's safety committee concluded its preliminary review about thromboembolic events in people vaccinated with COVID-19 Vaccine AstraZeneca at its extraordinary meeting, confirming the benefits of the vaccine continue to outweigh the risk of side effects, however, the vaccine may be associated with very rare cases of blood clots associated with thrombocytopenia, i.e., low levels of blood platelets with or without bleeding, including rare cases of cerebral venous thrombosis (CVT). We report the case of a 54-year-old woman who developed disseminated intravascular coagulation (DIC) with multi-district thrombosis 12 days after the AstraZeneca COVID-19 vaccine administration. A brain computed tomography (CT) scan showed multiple subacute intra-axial hemorrhages in atypical locations, including the right frontal and the temporal lobes. A plain old balloon angioplasty (POBA) of the right coronary artery was performed, without stent implantation, with restoration of distal flow, but with persistence of extensive thrombosis of the vessel. A successive thorax angio-CT added the findings of multiple contrast filling defects with multi-vessel involvement: at the level of the left upper lobe segmental branches, of left interlobar artery, of the right middle lobe segmental branches and of the right interlobar artery. A brain magnetic resonance imaging (MRI) in the same day showed the presence of an acute basilar thrombosis associated with the superior sagittal sinus thrombosis. An abdomen angio-CT showed filling defects at the level of left portal branch and at the level of right suprahepatic vein. Bilaterally, it was adrenal hemorrhage and blood in the pelvis. An evaluation of coagulation factors did not show genetic alterations so as the nasopharyngeal swab ruled out a COVID-19 infection. The patient died after 5 days of hospitalization in intensive care. [ABSTRACT FROM AUTHOR]