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Original article
Thrombosis with thrombocytopenia syndrome following adenovirus vector-based vaccines to prevent COVID-19: Epidemiology and clinical presentation in Spain
Síndrome de trombosis con trombocitopenia asociado a vacunas de adenovirus frente a la COVID-19: Epidemiología y presentación clínica de la serie española
D. García-Azorína,
Corresponding author
dgazorin@ucm.es

Corresponding author.
, E. Lázarob, D. Ezpeletac, R. Lecumberrid,e, R. de la Cámaraf, M. Castellanosg,h, C. Iñiguez Martínezi,j, L. Quiroga-Gonzálezb, G. Elizondo Rivask,l, A. Sancho-Lópezm,n,o, P. Rayón Iglesiasb, E. Segoviab, C. Mejíasb, D. Montero Corominasb
a Servicio de Neurología, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
b División de Farmacoepidemiología y Farmacovigilancia, Departamento de Medicamentos de Uso Humano, Agencia Española de Medicamentos y Productos Sanitarios, Madrid, Spain
c Servicio de Neurología, Hospital Universitario Quirónsalud Madrid, Pozuelo de Alarcón, Madrid, Spain
d Servicio de Hematología, Clínica Universidad de Navarra, Pamplona, Navarra, Spain
e CIBER-CV, Instituto de Salud Carlos III, Madrid, Spain
f Servicio de Hematología, Hospital de la Princesa, Madrid, Spain
g Servicio de Neurología, Complejo Hospitalario Universitario/Instituto de Investigación Biomédica de Coruña, Coruña, Spain
h Instituto de Salud Carlos III, Madrid, Spain
i Servicio de Neurología, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
j Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Zaragoza, Spain
k Centro de Farmacovigilancia de Navarra, Departamento de Salud, Gobierno de Navarra, Pamplona, Navarra, Spain
l Comité Técnico del Sistema Español de Farmacovigilancia, Spain
m Servicio de Farmacología Clínica, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain
n Sociedad Española de Farmacología Clínica (SECF), Spain
o Grupo de Vacunas de FACME, Madrid, Spain
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            1 => "COVID-19"
            2 => "Efectos adversos de medicamentos y reacciones adversas"
            3 => "Vacunas"
            4 => "Embolia y trombosis"
            5 => "Trastornos plaquetarios"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">We describe the epidemiological and clinical characteristics of thrombosis with thrombocytopenia syndrome &#40;TTS&#41; cases reported in Spain&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">We included all venous or arterial thrombosis with thrombocytopenia following adenovirus vector-based vaccines &#40;AstraZeneca or Janssen&#41; to prevent COVID-19 disease between February 1st and September 26th&#44; 2021&#46; We describe the crude rate and the standardized morbidity ratio&#46; We assessed the predictors of mortality&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Sixty-one cases were reported and 45 fulfilled eligibility criteria&#44; 82&#37; women&#46; The crude TTS rate was 4&#47;1&#44;000&#44;000 doses and 14-15&#47;1&#44;000&#44;000 doses between 30-49 years&#46; The number of observed cases of cerebral venous thrombosis was 6-18 higher than the expected in patients younger than 49 years&#46; Symptoms started 10 &#40;interquartile range &#40;IQR&#41;&#58; 7-14&#41; days after vaccination&#46; Eighty percent &#40;95&#37; confidence interval &#40;CI&#41;&#58; 65-90&#37;&#41; had thrombocytopenia at the time of the emergency department visit&#44; and 65&#37; &#40;95&#37; CI&#58; 49-78&#37;&#41; had D-dimer &#62;2000&#8201;ng&#47;mL&#46; Patients had multiple location thrombosis in 36&#37; and fatal outcome in 24&#37; cases&#46; A platelet nadir &#60;50&#44;000&#47;&#956;L &#40;odds ratio &#40;OR&#41;&#58; 7&#46;4&#59; CI 95&#37;&#58; 1&#46;2-47&#46;5&#41; and intracranial hemorrhage &#40;OR&#58; 7&#46;9&#59; IC95&#37;&#58; 1&#46;3-47&#46;0&#41; were associated with fatal outcome&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">TTS must be suspected in patients with symptoms 10 days after vaccination and thrombocytopenia and&#47;or D-dimer increase&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background"
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            "titulo" => "Methods"
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          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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            "identificador" => "abst0020"
            "titulo" => "Conclusion"
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      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Se describen las caracter&#237;sticas epidemiol&#243;gicas y cl&#237;nicas de los casos de s&#237;ndrome de trombosis con trombocitopenia &#40;STT&#41; notificados en Espa&#241;a&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron los casos de trombosis venosa o arterial con trombocitopenia tras recibir vacuna con vectores de adenovirus no replicantes frente a la COVID-19 &#40;AstraZeneca y Janssen&#41; del 1 de febrero al 26 de septiembre de 2021&#46; Se describe la tasa de notificaci&#243;n&#44; &#40;n&#250;mero de casos notificados&#47;n&#250;mero de dosis administradas&#41;&#44; y el an&#225;lisis de casos observados frente a esperados &#40;O&#47;E&#41;&#46; Se evaluaron los predictores de mortalidad&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">Se notificaron 61 casos&#44; cumpliendo 45 los criterios de elegibilidad&#44; 82&#37; mujeres&#46; La tasa de notificaci&#243;n global fue 4&#47;1&#46;000&#46;000 dosis y 14-15&#47;1&#46;000&#46;000 dosis entre los 30-49 a&#241;os&#46; El n&#250;mero de casos de trombosis de senos cerebrales observados fue 6-18 veces superior al esperado en menores de 49 a&#241;os&#46; Los s&#237;ntomas comenzaron 10 &#40;rango intercuart&#237;lico&#58; 7-14&#41; d&#237;as tras la vacunaci&#243;n&#46; El 80&#37; &#40;intervalo de confianza &#40;IC&#41; al 95&#37;&#58; 65-90&#37;&#41; ten&#237;a trombocitopenia en el momento de su visita a urgencias y el 65&#37; &#40;IC 95&#37;&#58; 49-78&#37;&#41; elevaci&#243;n del d&#237;mero D &#40;&#62; 2&#46;000&#8201;ng&#47;mL&#41;&#46; La trombosis fue de m&#250;ltiples localizaciones en 36&#37; y fatal en 24&#37; de los pacientes&#46; Un valor nadir de trombocitopenia &#60;50&#46;000&#47;&#956;L &#40;odds ratio &#40;OR&#41;&#58; 7&#44;4&#59; IC95&#37;&#58; 1&#44;2-47&#44;5&#41; y la presencia de hemorragia cerebral &#40;OR&#58; 7&#44;9&#59; IC95&#37;&#58; 1&#44;3-47&#44;0&#41; se asociaron a un desenlace fatal&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0120" class="elsevierStyleSimplePara elsevierViewall">Debe sospecharse el STT en pacientes que presenten s&#237;ntomas unos 10 d&#237;as tras la vacunaci&#243;n y presenten trombocitopenia y&#47;o elevaci&#243;n de d&#237;mero D&#46;</p></span>"
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Article information
ISSN: 21735808
Original language: English
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