Table 1. Table 1. Characteristics of the Patients.

Patient 1 was a 37-year-old woman with headaches that developed 1 week after vaccination with ChAdOx1 nCoV-19. At presentation to the emergency department the next day, she had fever and persistent headaches. She was found to have severe thrombocytopenia (Table 1). Computed tomography (CT) of the head showed thrombosis in the left transverse and sigmoid sinuses. Because of the low platelet count, a reduced dose of dalteparin (2500 IU daily) was given. The next day, her clinical condition deteriorated, and a new CT scan showed a massive cerebellar hemorrhage and edema in the posterior fossa. She was treated with platelet transfusions and decompressive craniectomy. During surgery, massive and uncontrollable edema developed. The patient died on day 2 after surgery.

Figure 1. Figure 1. Platelet Count Responses to Treatment. The vertical dashed line indicates the time at which the results of platelet factor 4 (PF4)–polyanion antibody tests were known. IVIG denotes intravenous immune globulin.

Patient 2 was a 42-year-old woman who had headaches 1 week after vaccination with ChAdOx1 nCoV-19. Her condition worsened rapidly, and she presented with reduced consciousness at presentation to the emergency department 3 days later. Her platelet count was 14,000 per cubic millimeter. ADAMTS13 activity was found to be normal. CT venography revealed venous thrombosis with occlusion of the transverse and sigmoid sinuses and hemorrhagic infarction in the left hemisphere. Hemicraniectomy was performed, and treatment with dalteparin at a dose of 2500 IU daily was initiated. She received multiple platelet transfusions over the following days. On day 8, methylprednisolone (1 mg per kilogram of body weight per day) and intravenous immune globulin (1 g per kilogram per day) were administered. The platelet count increased thereafter (Figure 1). However, the patient died after 2 weeks in the intensive care unit (ICU) from increased intracranial pressure and severe cerebral hemorrhagic infarction on day 15.

Patient 3, a 32-year-old man, presented to the emergency department with a backache 7 days after vaccination with ChAdOx1 nCoV-19. He had no preexisting conditions apart from asthma. No clinical signs of bleeding and no neurologic deficits were evident. Blood tests showed severe isolated thrombocytopenia (Table 1). A thoracoabdominal CT scan showed thrombosis of several branches of the portal vein with occlusion of the left intrahepatic portal vein and left hepatic vein. In addition, thrombosis was observed in the splenic vein, the azygos vein, and the hemiazygos vein. Contrast-enhanced magnetic resonance imaging (MRI) of the spine showed areas of hypointensity in several thoracic vertebrae and basivertebral veins, indicating compromised venous drainage. He was treated with intravenous immune globulin (1 g per kilogram per day for 2 days) and prednisolone (1 mg per kilogram per day). Dalteparin was administered at a dose of 5000 IU (one dose on the first day and two doses on the second day), after which the platelet count returned to normal and the dose was increased to 200 IU per kilogram per day (Figure 1). An abdominal CT scan indicated partial resolution of thrombosis. He was discharged from the hospital on day 12 in good health with warfarin and tapering doses of prednisolone.

Patient 4, a previously healthy 39-year-old woman who was vaccinated with ChAdOx1 nCoV-19, presented to the emergency department with abdominal pain and headaches 8 days after vaccination. A mild thrombocytopenia was revealed. An abdominal ultrasound examination was normal, and she was discharged. The headaches increased in intensity, and she returned to the emergency department 2 days later. Cerebral CT with venography showed massive thrombosis in the deep and superficial cerebral veins and right cerebellar hemorrhagic infarction. The platelet count was 70,000 per cubic millimeter. She was afebrile and had no signs of infection and no neurologic deficits. Treatment with dalteparin (200 IU per kilogram per day), prednisolone (1 mg per kilogram per day), and intravenous immune globulin (1 g per kilogram per day for 2 days) was started. The platelet count was normalized within 2 days (Figure 1). Follow-up CT venography showed recanalization in the affected cerebral venous sinuses. When she was discharged after 10 days, the symptoms had resolved. Her anticoagulation treatment was changed from dalteparin to warfarin, and treatment with prednisolone was continued in tapering doses.

Patient 5, a 54-year-old woman with a history of hypertension who was receiving hormone-replacement therapy, presented to the emergency department with stroke symptoms that had been present when she woke up from sleep, including hemiparesis on the left side of her body, 1 week after vaccination with ChAdOx1 nCoV-19. The platelet count was 19,000 per cubic millimeter, and CT of the head showed a right frontal hemorrhage. She received a platelet transfusion before she was transferred to our hospital, where treatment with methylprednisolone (1 mg per kilogram per day) and intravenous immune globulin (1 g per kilogram per day for 2 days) was commenced. A CT scan with venography showed a massive cerebral vein thrombosis with global edema and growth of hematoma (Table 1, and Fig. S1 in the Supplementary Appendix, available with the full text of this article at NEJM.org). Venous recanalization was achieved 4 hours after admission by endovascular intervention with thrombectomy after administration of 5000 IU of unfractionated heparin. During the procedure, a fully dilated right pupil was observed, and decompressive hemicraniectomy was performed immediately. Two days later, treatment was withdrawn because of an uncontrollable increase in intracranial pressure.