key: cord-0708322-mlfd2wcq authors: Blauenfeldt, Rolf Ankerlund; Kristensen, Søren Risom; Ernstsen, Siw Leiknes; Kristensen, Claudia Christina Hilt; Simonsen, Claus Ziegler; Hvas, Anne‐Mette title: Thrombocytopenia with acute ischemic stroke and bleeding in a patient newly vaccinated with an adenoviral vector‐based COVID‐19 vaccine date: 2021-05-05 journal: J Thromb Haemost DOI: 10.1111/jth.15347 sha: 2f7a7958f7c01ab21f80bd18af3ec34b932e350e doc_id: 708322 cord_uid: mlfd2wcq We describe the first Danish case of presumed inflammatory and thrombotic response to vaccination with an adenoviral (ChAdOx1) vector‐based COVID‐19 vaccine (AZD1222). The case describes a 60‐year‐old woman who was admitted with intractable abdominal pain 7 days after receiving the vaccine. Computed tomography of the abdomen revealed bilateral adrenal hemorrhages. On the following day, she developed a massive right‐sided ischemic stroke and magnetic resonance imaging angiography showed occlusion of the right internal carotid artery. The ischemic area was deemed too large to offer reperfusion therapy. During admission, blood tests showed a remarkable drop in platelet counts from 118,000 to 5000 per μl and a substantial increase in D‐dimer. The patient died on the sixth day of hospitalization. Blood tests revealed platelet factor 4 reactive antibodies, imitating what is seen in heparin‐induced thrombocytopenia. This may be a novel immune‐mediated response to the vaccine. On the second day of admission, she was last seen well in the afternoon and found 1 hour later with left-sided weakness and eye deviation to the right. A magnetic resonance imaging scan performed 2 hours after she was last seen well showed diffusion restriction and hence completed infarction in the entire area supplied by the right middle cerebral artery ( Figure S1 ). Because of the size of the infarct, it was deemed that reperfusion therapy could not be offered. A CT scan of the aorta excluded dissection. Treatment by hydrocortisone 100 mg three times daily as substitution therapy and cefuroxime was initiated. Platelet inhibitor treatment was deferred because of the possibility of malignant media infarction with subsequent surgery. On the third hospital day, her Glasgow Coma Scale score dropped from 12 to 5. CT of the cerebrum showed a malignant media infarction with a midline shift of 12 mm ( Figure S1 ). Blood tests (Table 1 ) showed a drop in platelet counts and the patient received three pools of platelet concentrates before hemicraniectomy. During admission, she received a total of seven pools of platelet concentrates. Hemicraniectomy was performed, but the patient did not regain consciousness. Postoperative dalteparin 5000 IU daily was started. On the fourth hospital day, the first through third fingers of the left hand were discolored dark/blue. The skin of the left foot was mottled with decreased capillary response. Follow-up CT scan of the cerebrum showed edema of the right hemisphere and no new ischemic or hemorrhagic lesions, but an unresolved midline shift. The patient was transferred to palliative care, in agreement with the family, and died on the sixth hospital day. A vaccine activates the immune system, and unwanted side effects are often seen. Common side effects may include pain at the injection site, headache, muscle and joint pain, and general feeling of being unwell. Rarely, autoimmune diseases may be elicited such as Guillain-Barré syndrome. 7 Anaphylactic shock with vasodilation and hypotension is the most feared side effect, and rapid identification and treatment can be life-saving. The syndrome suffered by the patient in this case, has to our knowledge, not previously been described in the medical literature as a potential postvaccination reaction. It is a highly unique and a rarely seen reaction with a temporal relation to vaccination. Therefore, an association between vaccination and the clinical syndrome is suspected. Several differential diagnoses were considered. Infectious and noninfectious endocarditis was unlikely, given normal blood cultures and a normal transthoracic echocardiography. Septicemia and in particular Waterhouse-Friedrichsen syndrome with adrenal hemorrhages caused by meningococcal disease was also unlikely, given normal blood culture and negative Neisseria meningitidis antibody. Aortic dissection was ruled out by a CT scan of the aorta. Thrombotic thrombocytopenic purpura was ruled out by a normal blood smear and a normal a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 level. Catastrophic antiphospholipid syndrome was considered, but tests for lupus anti- • We describe the first-ever case of presumed immune mediated thrombocytopenia, hemorrhage, and ischemic stroke after vaccination with an adenoviral (ChAdOx1) vector based COVID-19 vaccine (AZD1222). • Thrombocytopenia with thrombosis and bleeding may be a novel immune-mediated response to an adenoviral vector-based COVID-19 vaccine, resembling heparin-induced thrombocytopenia. • The presence of platelet factor 4 antibodies was confirmed. TA B L E 1 Blood tests during the admission of a 60-year-old woman with ischemic stroke and immune-mediated thrombocytopenia following vaccination ses in the published papers were mainly venous thromboses. This case demonstrates that a primary arterial thrombosis also may be a complication. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK Norwegian doctors are investigating if blood clots could be linked to the AstraZeneca-vaccine Researchers from Greifswald Germany report breakthrough in SARS-CoV2 vaccination related thrombotic complications Guillain-Barré syndrome following influenza vaccination Testing for heparin-induced thrombocytopenia antibodies Autoimmune heparininduced thrombocytopenia Management of heparin-induced thrombocytopenia Neutrophil activation and NETosis are the major drivers of thrombosis in heparin-induced thrombocytopenia Heparin-induced thrombocytopenia in severe COVID-19 Thrombocytopenia with acute ischemic stroke and bleeding in a patient newly vaccinated with an adenoviral vectorbased COVID-19 vaccine