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      Rapid progressive vaccine-induced immune thrombotic thrombocytopenia with cerebral venous thrombosis after ChAdOx1 nCoV-19 (AZD1222) vaccination: A case report

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          Abstract

          BACKGROUND

          Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare and potentially life-threatening condition after receiving coronavirus disease vaccines. It is characterized by symptom onset at 5 to 30 d postvaccination, thrombocytopenia, thrombosis, high D-dimer level, and antiplatelet factor 4 (anti-PF4) antibody positivity. VITT can progress very fast, requiring urgent management. Only few studies have described its detailed clinical course and imaging changes. We report a typical VITT case in a patient who underwent regular repeated brain imaging examinations.

          CASE SUMMARY

          A young woman presented with headaches at 7 d after the ChAdOx1 nCoV-19 vaccine (AZD1222) injection. She then showed progressive symptoms of left upper limb clumsiness. Brain computed tomography revealed venous infarction at the right parietal lobe with a hyperacute thrombus in the cortical vein. Two hours later, brain magnetic resonance imaging revealed hemorrhage at the same area. Magnetic resonance venography showed an irregular contour of the right transverse sinus. Laboratory examination revealed a high D-dimer level, thrombocytopenia, and a high titer for anti-PF4 antibodies. She was treated with anticoagulants, intravenous immunoglobulin, and steroids and analgesic agents were administered for pain control. She had a marked improvement on headaches and clumsiness after treatment along with radiological thrombus resolution. During follow-up at the outpatient department, her modified Rankin scale at 90 d was 1.

          CONCLUSION

          Clinicians should be alerted whenever patients present with persistent and progressive headaches or focal motor/sensory deficits postvaccination.

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          Most cited references15

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          Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination

          Background Several cases of unusual thrombotic events and thrombocytopenia have developed after vaccination with the recombinant adenoviral vector encoding the spike protein antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (ChAdOx1 nCov-19, AstraZeneca). More data were needed on the pathogenesis of this unusual clotting disorder. Methods We assessed the clinical and laboratory features of 11 patients in Germany and Austria in whom thrombosis or thrombocytopenia had developed after vaccination with ChAdOx1 nCov-19. We used a standard enzyme-linked immunosorbent assay to detect platelet factor 4 (PF4)–heparin antibodies and a modified (PF4-enhanced) platelet-activation test to detect platelet-activating antibodies under various reaction conditions. Included in this testing were samples from patients who had blood samples referred for investigation of vaccine-associated thrombotic events, with 28 testing positive on a screening PF4–heparin immunoassay. Results Of the 11 original patients, 9 were women, with a median age of 36 years (range, 22 to 49). Beginning 5 to 16 days after vaccination, the patients presented with one or more thrombotic events, with the exception of 1 patient, who presented with fatal intracranial hemorrhage. Of the patients with one or more thrombotic events, 9 had cerebral venous thrombosis, 3 had splanchnic-vein thrombosis, 3 had pulmonary embolism, and 4 had other thromboses; of these patients, 6 died. Five patients had disseminated intravascular coagulation. None of the patients had received heparin before symptom onset. All 28 patients who tested positive for antibodies against PF4–heparin tested positive on the platelet-activation assay in the presence of PF4 independent of heparin. Platelet activation was inhibited by high levels of heparin, Fc receptor–blocking monoclonal antibody, and immune globulin (10 mg per milliliter). Additional studies with PF4 or PF4–heparin affinity purified antibodies in 2 patients confirmed PF4-dependent platelet activation. Conclusions Vaccination with ChAdOx1 nCov-19 can result in the rare development of immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, which clinically mimics autoimmune heparin-induced thrombocytopenia. (Funded by the German Research Foundation.)
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            Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination

            We report findings in five patients who presented with venous thrombosis and thrombocytopenia 7 to 10 days after receiving the first dose of the ChAdOx1 nCoV-19 adenoviral vector vaccine against coronavirus disease 2019 (Covid-19). The patients were health care workers who were 32 to 54 years of age. All the patients had high levels of antibodies to platelet factor 4–polyanion complexes; however, they had had no previous exposure to heparin. Because the five cases occurred in a population of more than 130,000 vaccinated persons, we propose that they represent a rare vaccine-related variant of spontaneous heparin-induced thrombocytopenia that we refer to as vaccine-induced immune thrombotic thrombocytopenia.
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              Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination

              Background The mainstay of control of the coronavirus disease 2019 (Covid-19) pandemic is vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Within a year, several vaccines have been developed and millions of doses delivered. Reporting of adverse events is a critical postmarketing activity. Methods We report findings in 23 patients who presented with thrombosis and thrombocytopenia 6 to 24 days after receiving the first dose of the ChAdOx1 nCoV-19 vaccine (AstraZeneca). On the basis of their clinical and laboratory features, we identify a novel underlying mechanism and address the therapeutic implications. Results In the absence of previous prothrombotic medical conditions, 22 patients presented with acute thrombocytopenia and thrombosis, primarily cerebral venous thrombosis, and 1 patient presented with isolated thrombocytopenia and a hemorrhagic phenotype. All the patients had low or normal fibrinogen levels and elevated d -dimer levels at presentation. No evidence of thrombophilia or causative precipitants was identified. Testing for antibodies to platelet factor 4 (PF4) was positive in 22 patients (with 1 equivocal result) and negative in 1 patient. On the basis of the pathophysiological features observed in these patients, we recommend that treatment with platelet transfusions be avoided because of the risk of progression in thrombotic symptoms and that the administration of a nonheparin anticoagulant agent and intravenous immune globulin be considered for the first occurrence of these symptoms. Conclusions Vaccination against SARS-CoV-2 remains critical for control of the Covid-19 pandemic. A pathogenic PF4-dependent syndrome, unrelated to the use of heparin therapy, can occur after the administration of the ChAdOx1 nCoV-19 vaccine. Rapid identification of this rare syndrome is important because of the therapeutic implications.
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                Author and article information

                Contributors
                Journal
                World J Clin Cases
                WJCC
                World Journal of Clinical Cases
                Baishideng Publishing Group Inc
                2307-8960
                16 September 2022
                16 September 2022
                : 10
                : 26
                : 9462-9469
                Affiliations
                Department of Neurology, China Medical University Hospital, Taichung 404332, Taiwan
                Department of Radiology, China Medical University Hospital, Taichung 404332, Taiwan
                Department of Neurology, China Medical University Hsinchu Hospital, Hsinchu 30272, Taiwan
                Department of Emergency, China Medical University Hospital, Taichung 404332, Taiwan
                Department of Neurology, China Medical University Hospital, Taichung 404332, Taiwan
                Neuroscience and Brain Disease Center, China Medical University, Taichung 404332, Taiwan. tshengdar@ 123456gmail.com
                Author notes

                Author contributions: Jiang SK and Tsai ST were the patient’s chief attending doctor during hospitalization, collected the patient‘s clinical data, reviewed the literature, and contributed to manuscript drafting; Jiang SK drafted the manuscript; Pan CS was the doctor in emergency department who evaluated her first and was alert to this syndrome; Chien C reviewed the literature and contributed to manuscript drafting; Chen WL analyzed and interpreted the imaging findings and he was consulted for endovascular therapy; Tsai ST was responsible for the revision of the manuscript for important intellectual content; and All authors issued final approval for the version to be submitted.

                Corresponding author: Sheng-Ta Tsai, MD, PhD, Attending Doctor, Department of Neurology, China Medical University Hospital, No. 2 Yude Road, North District, Taichung 404332, Taiwan. tshengdar@ 123456gmail.com

                Article
                jWJCC.v10.i26.pg9462
                10.12998/wjcc.v10.i26.9462
                9477691
                36159410
                73e6a6e3-7ac0-45fd-b4a8-af6697f6972a
                ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

                History
                : 26 April 2022
                : 20 June 2022
                : 1 August 2022
                Categories
                Case Report

                vaccine-induced immune thrombotic thrombocytopenia,intracranial sinus thrombosis,chadox1 ncov-19 vaccine (azd1222),headache,serial brain image,case report

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