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      Trombocitopenia Trombótica Imune Induzida pela Vacina Contra a COVID-19 Translated title: SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia

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          Abstract

          Resumo Um ano depois de declarada pandemia pela Organização Mundial da Saúde, surgiram as primeiras vacinas contra o vírus SARS-CoV-2. Na literatura, dados referentes ao Reino Unido e aos Estados Unidos da América (EUA) sugerem que a vacinação - uma ou duas doses - reduziu as hospitalizações entre 67% e 94%. Em fevereiro de 2021 foram descritos os primeiros casos de trombocitopenia e trombose em locais atípicos, nomeadamente a nível do seio venoso cerebral e na circulação venosa esplâncnica, associadas à toma da vacina. Os primeiros estudos nos EUA sugerem uma incidência (provavelmente subestimada) de 1 em 533 333/indivíduos vacinados. Apesar de incomum, é um efeito adverso grave com alta taxa de mortalidade, estimada em 20%, em parte pelo diagnóstico tardio, pois a clínica inicial é muitas vezes inespecífica e frustre. Este relato de caso salienta a necessidade de um elevado índice de suspeição ab initio, que pode mudar o prognóstico destes doentes.

          Translated abstract

          Abstract The first vaccines against the SARS-CoV-2 virus appea-red one year after the WHO declared COVID-19 as a pandemic, with data from United Kingdom and United States of America (USA) reporting a reduction in hospitalization about 67% e 94%, with one or two doses of an approved vaccine. In February 2021, the first cases of thrombocytopenia and thrombosis at uncommon sites (cerebral venous sinus and splanchnic venous thrombosis) induced by the vaccines were described. The incidence is still unknown, but early studies in the USA suggest an incidence of 1 in 533 333/vaccinated individuals, and this is probably underestimated. Although un-common, it is a serious adverse effect with a high mortality rate, estimated at 20%. This case report highlights the need for a high level of suspicion, which may change the prognosis of some of these patients.

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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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            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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              SARS-CoV-2 Vaccine–Induced Immune Thrombotic Thrombocytopenia

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                Author and article information

                Journal
                mint
                Medicina Interna
                Medicina Interna
                Sociedade Portuguesa de Medicina Interna (Lisboa, , Portugal )
                0872-671X
                December 2022
                : 29
                : 4
                : 19-23
                Affiliations
                [3] Porto orgnameCentro Hospitalar e Universitário do Porto orgdiv1Serviço Medicina Interna e Medicina Intensiva Portugal
                [2] Porto orgnameCentro Hospitalar e Universitário do Porto orgdiv1Serviço de Neurorradiologia Portugal
                [1] Porto orgnameCentro Hospitalar e Universitário do Porto orgdiv1Serviço de Medicina Interna Portugal
                Article
                S0872-671X2022000400019 S0872-671X(22)02900400019
                10.24950/rspmi.227
                10926a36-0b39-4931-96fc-bd47e91ee75a

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 18 February 2022
                : 17 December 2021
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 10, Pages: 5
                Product

                SciELO Portugal

                Categories
                Casos Clínicos/ Case Reports

                Trombose Venosa,Vacina contra COVID-19/efeitos adversos.,COVID-19 Vaccines/adverse effects,COVID-19/prevention & control,SARS-CoV-2,Venous Thrombosis,Thrombocytopenia/chemically induced.,COVID/prevenção e controlo,SARS--CoV-2,Trombocitopenia/induzida quimicamente

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