Intracerebral Hemorrhage due to Thrombosis with Thrombocytopenia Syndrome after Vaccination against COVID-19: the First Fatal Case in Korea

Abstract

Vaccination with an adenoviral vector vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can result in the rare development of thrombosis with thrombocytopenia mediated by platelet-activating antibodies against platelet factor 4 (PF4). This is a life-threating condition that may be accompanied by bleeding due to thrombocytopenia with thrombosis of the cerebral venous sinus or splanchnic vein. Herein, we describe the first fatal case of thrombosis with thrombocytopenia syndrome in Korea, presenting with intracranial hemorrhage caused by cerebral venous sinus thrombosis. A 33-year-old Korean man received the first dose of the ChAdOx1 nCoV-19 vaccination. He developed severe headache with vomiting 9 days after the vaccination. Twelve days after vaccination, he was admitted to the hospital with neurological symptoms and was diagnosed with cerebral venous sinus thrombosis, which was accompanied by intracranial hemorrhage. Thrombocytopenia and D-dimer elevation were observed, and the result of the PF4 enzyme-linked immunosorbent assay antibody test was reported to be strongly positive. Despite intensive treatment, including intravenous immunoglobulin injection and endovascular mechanical thrombectomy, the patient died 19 days after vaccination. Physicians need to be aware of thrombosis with thrombocytopenia syndrome (TTS) in adenoviral vector-vaccinated patients. Endovascular mechanical thrombectomy might be a useful therapeutic option for the treatment of TTS with cerebral venous sinus thrombosis.

Stroke Associated with COVID-19 Vaccines

“…Wolf et al ( 106) reported 3 cases of CVT after COVID-19 vaccination who were successfully treated by endovascular rheolysis. Although the outcome of EMT in the case report by Choi et al (105) was not satisfactory, they suggested that if the EMT is done at early stages, and before the beginning of cortical venous occlusion, the outcome might be better. Therefore, if VITT-associated CVT is clinically suspected and the symptoms deteriorate quickly, early EMT intervention is necessary (105).…”

“…Although the outcome of EMT in the case report by Choi et al (105) was not satisfactory, they suggested that if the EMT is done at early stages, and before the beginning of cortical venous occlusion, the outcome might be better. Therefore, if VITT-associated CVT is clinically suspected and the symptoms deteriorate quickly, early EMT intervention is necessary (105). Another non-pharmacological procedure is decompressive craniectomy, which should be decided based on the patient's condition.…”

“…The use of non-heparin anticoagulants and IVIg can be related to a low probability of VITT-associated CVT death or dependency at the end of hospital admission (92). IVIg prevents platelet activation by PF4 antibodies and rapidly restores the platelet count (105). Immune globulin prevents antibody-mediated platelet clearance and may down-regulate platelet activation by immune complexes by blocking platelet FcRγIIA receptors (127).…”

Vaccination of elite athletes against SARS-CoV-2 and broader implications for public health policy

“…Acute transverse myelitis (ATM) has been reported at a higher than expected rate following vaccination with AZD1222 (104). Thrombotic-thrombocytopenia, resultant hemorrhage and sequelae such as ischemic stroke and death have been reported after vaccination with AZD1222 (105,106,107). Gam--COVID--Vac (Sputnik V) is a SARS--CoV--2 viral vector nucleotide vaccine, which utilizes a hybrid approach to viral delivery of a DNA template encoding SARS--CoV--2 spike protein (73,103).…”

Cerebral Venous Sinus Thrombosis following COVID-19 Vaccination: Analysis of 552 Worldwide Cases

“…Overall, positive outcomes were reported in no-stroke patients. Advanced endovascular procedures such as rheolysis, flushing, and aspiration with 50% saline solution with contrast medium [49] or mechanical thrombectomy [19] were attempted throughout the jugular vein.…”