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Ischemic stroke was a presenting feature of vaccine-induced thrombosis and thrombocytopenia (VITT) in three patients who received the AstraZeneca COVID-19 vaccine, researchers in England said.

Previous descriptions of VITT have largely involved cerebral venous sinuses, but characteristics of VITT with arterial thrombosis have not been previously described, wrote David Werring, PhD, of UCL Queen Square Institute of Neurology in London, and colleagues, in a letter to the .

"This case series shows that ischemic stroke -- the commonest type, due to blockage of an artery supplying the brain -- can be the presenting feature of the recently recognized syndrome," Werring told 麻豆传媒.

"Doctors and people receiving the vaccine should be aware that ischemic stroke can be a sign of VITT," he said. "Ischemic stroke as part of VITT needs to be recognized quickly because there are specific treatments, including immunoglobulins, plasma exchange, and anticoagulants, that can improve the outcome."

VITT is a rare syndrome associated with the AstraZeneca adenoviral vector vaccine, which uses a chimpanzee adenovirus-based vector. It is used in England and other countries but not the U.S. Cerebral venous sinus thrombosis also has been reported in people who received the , which uses a human adenovirus-based vector.

"The risk of VITT remains very low -- about one in 100,000 -- and is far outweighed by the proven benefits of vaccination in protecting against COVID-19," Werring said.

Previously showed VITT has key characteristics that include low platelet counts and the presence of platelet factor 4 (PF4) antibodies.

In this case series, all three patients with arterial thrombosis had extremely low platelet counts, confirmed anti-PF4 antibodies, and raised D-dimer levels. Ischemic stroke was associated with blockages of carotid and middle cerebral arteries. Two people also had venous thrombosis.

The first patient, a 35-year-old Asian woman, experienced intermittent headache on her right side and around her eyes 6 days after vaccination. Five days later, she woke with drowsiness and left face, arm, and leg weakness. Imaging showed right middle cerebral artery occlusion with extensive ischemia and right portal vein thrombosis. After urgent decompressive hemicraniectomy, IV immunoglobulin, and plasmapheresis, she received anticoagulation with fondaparinux. Fourteen days after presentation, her conscious level dropped suddenly and she died.

The second, a 37-year-old woman, presented with diffuse headache, confusion, weakness in her left arm, and left visual field loss 12 days after receiving the vaccine. Imaging showed occlusion of bilateral internal carotid arteries, left transverse sinus thrombosis, pulmonary embolism, and thromboses of the left transverse and sigmoid sinuses, left jugular, right hepatic, and both iliac veins. Platelets increased after treatment with IV immunoglobulin, methylprednisolone, and plasmapheresis. She then received fondaparinux and improved clinically.

The third patient was a 43-year-old Asian man who presented 21 days after vaccination with dysphasia. Imaging showed acute left frontal and insular infarct with no evidence of cerebral venous sinus thrombosis. He received platelet transfusion, IV immunoglobulin, and fondaparinux, and remains clinically stable.

COVID-19 itself is a risk factor for stroke, occurring in 1.4% of SARS-CoV-2 infections, noted Hugh Markus, MD, of the University of Cambridge in England, in an .

"During the current period of COVID-19 vaccination, a high index of suspicion is required to identify thrombotic episodes following vaccination," he wrote. "However, it is important to remember that these side effects are rare and much less common than both cerebral venous thrombosis and ischemic stroke associated with COVID-19 infection itself, as illustrated by a recent large epidemiological study."

Patients presenting with ischemic stroke after receiving the Oxford-AstraZeneca vaccine should urgently be evaluated for VITT with laboratory tests for platelet count, D-dimers, fibrinogen, and anti-PF4 antibodies, Werring said.

"Patients must also be managed by a multidisciplinary team, including hematology, neurology, stroke, neurosurgery, and neuroradiology, for rapid access to potentially lifesaving treatments including intravenous immune globulin, methylprednisolone, plasmapheresis, and non-heparin anticoagulants, for example fondaparinux, argatroban, or direct oral anticoagulants," he added.

In the U.S., the CDC has cautioned that patients with a prior history of an episode of an immune-mediated syndrome characterized by thrombocytopenia and thrombosis (like heparin-induced thrombocytopenia) should avoid the Johnson & Johnson COVID-19 vaccine in the immediate aftermath of their illness. The agency also has partnered with the American Society of Hematology to provide information about recommendations.

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