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      Trombosis venosa profunda durante el periodo de vacunación frente al virus SARS-CoV-2 Translated title: Deep vein thrombosis during vaccination against SARS-CoV-2 period

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          Abstract

          Resumen Objetivos: tras el inicio de la vacunación frente al SARS-CoV-2 una de las entidades de enfermedad tromboembólica venosa (ETEV) más frecuente, la trombosis venosa profunda (TVP), apenas ha sido documentada. Analizamos los episodios de TVP durante el periodo de vacunación frente al SARS-CoV-2. Material y métodos: análisis unicéntrico retrospectivo que incluye pacientes diagnosticados de TVP (enero-septiembre de 2021). Se estratifican en dos grupos: vacunados y no vacunados frente al SARS-CoV-2 en los 28 días anteriores a iniciar la sintomatología de TVP. Variable principal: gravedad de TVP (tromboembolismo pulmonar [TEP] o necesidad de ingreso). Variables secundarias: factores de riesgo para TVP (idiopática, antecedente de ETEV, encamamiento, traumatismo, cirugía, trombofilia, hormonoterapia y neoplasia). Resultados: 192 pacientes diagnosticados de TVP, 42 (21,9 %) vacunados y 150 (78,1 %) no vacunados. Desarrollaron TEP el 52,4 % de los vacunados y el 62,7 % de los controles (p = 0,228). Necesidad de ingreso: 52,4 % de los vacunados frente al 62,4 % de los no vacunados) (p = 0,536); TVP idiopática: 28,6 % de los vacunados frente al 48 % de los no vacunados) (p = 0,025); antecedente de ETEV: 21,4 % de los vacunados frente al 17,3 % de los controles) (p = 0,543); encamamiento: 7,1 % de los vacunados frente al 12,7 % de los no vacunados (p = 0,418); traumatismo: 4,8 % de los vacunados frente al 6 % de los controles (p = 1); cirugía: 4,8 % de los vacunados frente al 1,3 % de los no vacunados (p = 0,209); trombofilia: 16,7 % de los vacunados frente al 4 % de los controles (p = 0,009); hormonoterapia: 9,5 % de los vacunados frente al 3,3 % de los no vacunados (p = 0,107); neoplasia: 28,6 % de los vacunados frente al 18,7 % de los no vacunados (p = 0,162). Se apreció un OR 6,10 (IC 95 %, 1,52-24,37) para TVP en pacientes vacunados con trombofilia en el análisis multivariante. Conclusión: la vacunación frente SARS-CoV-2 no parece aumentar la gravedad de la TVP, aunque se aprecia un aumento de la incidencia de TVP en pacientes vacunados con trombofilia.

          Translated abstract

          Abstract Objectives: since the beginning of vaccination against SARS-CoV-2 virus one of the most frequent entities of venous thromboembolism (VTE), deep vein thrombosis (DVT), has been scarcely documented. We analyze DVT episodes during vaccination against SARS-CoV-2 period. Material and methods: retrospective unicenter analysis including patients diagnosed with DVT (January -September 2021). Patients were divided into two groups, vaccinated and unvaccinated against SARS-CoV-2 28 days prior to DVT symptoms onset. Primary endpoint: DVT severity (pulmonary embolism (PE) and/or hospital admission). Secondary endpoints: DVT risk factors (unprovoked, VTE antecedent, immobilization, trauma, surgery, thrombophilia, hormone therapy and cancer). Results: there were 192 DVT diagnoses, 42 (21,9 %) vaccinated and 150 (78,1 %) unvaccinated. DVT severity: PE: 52,4 % vaccinated vs. 62,7 % controls (p = 0,228); hospital admission: 52,4 % vaccinated vs. 62,4 % unvaccinated (p = 0,536); unprovoked DVT: 28,6 % vaccinated vs. 48 % unvaccinated (p = 0,025); VTE antecedent: 21,4 % vaccinated vs. 17,3 % unvaccinated (p = 0,543): immobilization: 7,1 % vaccinated vs. 12,7 % unvaccinated; trauma: 4,8 % vaccinated vs. 6 % unvaccinated (p = 1); surgery: 4,8 % vaccinated vs. 1,3 % unvaccinated (p = 0,209); thrombophilia: 16,7 % vaccinated vs. 4 % unvaccinaed (p = 0,009); hormone theraphy: 9,5 % vaccinated vs. 3,3 % unvaccinated (p = 0,107); cancer: 28,6 % vaccinated vs. 18,7 % unvaccinated (p = 0,162). Multivariate analysis showed a higher risk of DVT in vaccinated patients with thrombophilia, with an OR of 6,10 (95 % CI, 1,52-24,37). Conclusion: vaccination against SARS-CoV-2 doesn’t seem to increased DVT severity, although a higher incidence of DVT in vaccinated patients with thrombophilia was observed.

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          Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

          Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)
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            Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

            Abstract Background Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. Methods This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. Results The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups. Conclusions The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.)
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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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                Author and article information

                Journal
                angiologia
                Angiología
                Angiología
                Arán Ediciones S.L. (Madrid, Madrid, Spain )
                0003-3170
                1695-2987
                February 2023
                : 75
                : 1
                : 11-18
                Affiliations
                [1] Zaragoza orgnameHospital Universitario Miguel Servet orgdiv1Cirugía Vascular y Endovascular orgdiv2Servicio de Angiología España
                [2] Mallorca orgnameHospital Universitari Son Espases orgdiv1Cirugía Vascular y Endovascular orgdiv2Servicio de Angiología España
                Article
                S0003-31702023000100011 S0003-3170(23)07500100011
                10.20960/angiologia.00460
                29678b9b-59f8-4d69-8014-3b364a69bfc2

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

                History
                : 31 July 2022
                : 01 September 2022
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 23, Pages: 8
                Product

                SciELO Spain

                Categories
                Originales

                Trombosis venosa profunda,COVID-19,Vacuna,Hemodiálisis,Deep vein thrombosis,Vaccine,Hemodialysis

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