array:23 [ "pii" => "S002577531930123X" "issn" => "00257753" "doi" => "10.1016/j.medcli.2019.01.029" "estado" => "S300" "fechaPublicacion" => "2019-11-29" "aid" => "4776" "copyright" => "Elsevier España, S.L.U." "copyrightAnyo" => "2019" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Med Clin. 2019;153:373-9" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 11 "formatos" => array:2 [ "HTML" => 5 "PDF" => 6 ] ] "Traduccion" => array:1 [ "en" => array:19 [ "pii" => "S2387020619304644" "issn" => "23870206" "doi" => "10.1016/j.medcle.2019.01.042" "estado" => "S300" "fechaPublicacion" => "2019-11-29" "aid" => "4776" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Med Clin. 2019;153:373-9" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Gynaecological and obstetrical bleeding in Caucasian women with congenital factor XI deficiency: Results from a twenty-year, retrospective, observational study" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "373" "paginaFinal" => "379" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hemorragia ginecológica y obstétrica en mujeres caucásicas con deficiencia congénita de factor XI: Resultados de veinte años de registro observacional y retrospectivo" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 3505 "Ancho" => 2854 "Tamanyo" => 446231 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Graphic representation of cases with gynaecological/obstetrical bleeding episodes according to FXI:C quintiles (A–C) and ROC curves for optimal FXI:C levels cut-off selection (D–F). Abnormal uterine bleeding (A, D), postpartum haemorrhage (B, E) and postsurgical haemorrhage (C, F) showed an association with FXI:C activity, with a common FXI:C level cut-off at 43.5%. FXI: factor XI; FXI:C: FXI clotting activity; ROC: receiver-operating-characteristic.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Carlos Bravo-Perez, Teresa Ródenas, Julio Esteban, Maria Eugenia de la Morena-Barrio, Salam Salloum-Asfar, Belen de la Morena-Barrio, Antonia Miñano, Vicente Vicente, Javier Corral" "autores" => array:9 [ 0 => array:2 [ "nombre" => "Carlos" "apellidos" => "Bravo-Perez" ] 1 => array:2 [ "nombre" => "Teresa" "apellidos" => "Ródenas" ] 2 => array:2 [ "nombre" => "Julio" "apellidos" => "Esteban" ] 3 => array:2 [ "nombre" => "Maria Eugenia" "apellidos" => "de la Morena-Barrio" ] 4 => array:2 [ "nombre" => "Salam" "apellidos" => "Salloum-Asfar" ] 5 => array:2 [ "nombre" => "Belen" "apellidos" => "de la Morena-Barrio" ] 6 => array:2 [ "nombre" => "Antonia" "apellidos" => "Miñano" ] 7 => array:2 [ "nombre" => "Vicente" "apellidos" => "Vicente" ] 8 => array:2 [ "nombre" => "Javier" "apellidos" => "Corral" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S002577531930123X" "doi" => "10.1016/j.medcli.2019.01.029" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S002577531930123X?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020619304644?idApp=UINPBA00004N" "url" => "/23870206/0000015300000010/v1_201911230806/S2387020619304644/v1_201911230806/en/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S0025775319301307" "issn" => "00257753" "doi" => "10.1016/j.medcli.2019.02.003" "estado" => "S300" "fechaPublicacion" => "2019-11-29" "aid" => "4783" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Med Clin. 2019;153:380-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 4 "HTML" => 4 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Antibody responses to influenza vaccine in patients on biological therapy: Results of RIER cohort study" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "380" "paginaFinal" => "386" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Respuesta a la vacuna contra la gripe en pacientes que reciben tratamientos biológicos: resultados del estudio de cohortes RIER" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 730 "Ancho" => 1501 "Tamanyo" => 49089 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Percentage of patients with final detectable Ab depending on the biological agent: *<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.024.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Patricia Richi, María Dolores Martín, María Teresa Navío, Laura González-Hombrado, Marina Salido, Jesús Llorente, Israel Thuissard-Vasallo, Patricia Alcocer, Carmen María Saa-Requejo, Ana Jiménez-Diaz, Laura Cebrián, Leticia Lojo, Marta García-Castro, David Sanz-Rosa, Patricia Castro, Sandra Fernández-Rodríguez, María José Martínez de Aramayona, Martina Steiner, Tatiana Cobo, Cristina García-Fernández, Mónica Fernández-Castro, Óscar Illera, Ricardo Valverde, Santiago Muñoz-Fernández" "autores" => array:24 [ 0 => array:2 [ "nombre" => "Patricia" "apellidos" => "Richi" ] 1 => array:2 [ "nombre" => "María Dolores" "apellidos" => "Martín" ] 2 => array:2 [ "nombre" => "María Teresa" "apellidos" => "Navío" ] 3 => array:2 [ "nombre" => "Laura" "apellidos" => "González-Hombrado" ] 4 => array:2 [ "nombre" => "Marina" "apellidos" => "Salido" ] 5 => array:2 [ "nombre" => "Jesús" "apellidos" => "Llorente" ] 6 => array:2 [ "nombre" => "Israel" "apellidos" => "Thuissard-Vasallo" ] 7 => array:2 [ "nombre" => "Patricia" "apellidos" => "Alcocer" ] 8 => array:2 [ "nombre" => "Carmen María" "apellidos" => "Saa-Requejo" ] 9 => array:2 [ "nombre" => "Ana" "apellidos" => "Jiménez-Diaz" ] 10 => array:2 [ "nombre" => "Laura" "apellidos" => "Cebrián" ] 11 => array:2 [ "nombre" => "Leticia" "apellidos" => "Lojo" ] 12 => array:2 [ "nombre" => "Marta" "apellidos" => "García-Castro" ] 13 => array:2 [ "nombre" => "David" "apellidos" => "Sanz-Rosa" ] 14 => array:2 [ "nombre" => "Patricia" "apellidos" => "Castro" ] 15 => array:2 [ "nombre" => "Sandra" "apellidos" => "Fernández-Rodríguez" ] 16 => array:2 [ "nombre" => "María José" "apellidos" => "Martínez de Aramayona" ] 17 => array:2 [ "nombre" => "Martina" "apellidos" => "Steiner" ] 18 => array:2 [ "nombre" => "Tatiana" "apellidos" => "Cobo" ] 19 => array:2 [ "nombre" => "Cristina" "apellidos" => "García-Fernández" ] 20 => array:2 [ "nombre" => "Mónica" "apellidos" => "Fernández-Castro" ] 21 => array:2 [ "nombre" => "Óscar" "apellidos" => "Illera" ] 22 => array:2 [ "nombre" => "Ricardo" "apellidos" => "Valverde" ] 23 => array:2 [ "nombre" => "Santiago" "apellidos" => "Muñoz-Fernández" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2387020619304656" "doi" => "10.1016/j.medcle.2019.02.031" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020619304656?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775319301307?idApp=UINPBA00004N" "url" => "/00257753/0000015300000010/v1_201911090636/S0025775319301307/v1_201911090636/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Gynaecological and obstetrical bleeding in Caucasian women with congenital factor XI deficiency: Results from a twenty-year, retrospective, observational study" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "373" "paginaFinal" => "379" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Carlos Bravo-Perez, Teresa Ródenas, Julio Esteban, Maria Eugenia de la Morena-Barrio, Salam Salloum-Asfar, Belen de la Morena-Barrio, Antonia Miñano, Vicente Vicente, Javier Corral" "autores" => array:9 [ 0 => array:2 [ "nombre" => "Carlos" "apellidos" => "Bravo-Perez" ] 1 => array:2 [ "nombre" => "Teresa" "apellidos" => "Ródenas" ] 2 => array:2 [ "nombre" => "Julio" "apellidos" => "Esteban" ] 3 => array:2 [ "nombre" => "Maria Eugenia" "apellidos" => "de la Morena-Barrio" ] 4 => array:2 [ "nombre" => "Salam" "apellidos" => "Salloum-Asfar" ] 5 => array:2 [ "nombre" => "Belen" "apellidos" => "de la Morena-Barrio" ] 6 => array:2 [ "nombre" => "Antonia" "apellidos" => "Miñano" ] 7 => array:4 [ "nombre" => "Vicente" "apellidos" => "Vicente" "email" => array:1 [ 0 => "vicente.vicente@carm.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 8 => array:2 [ "nombre" => "Javier" "apellidos" => "Corral" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Murcia, CIBERER, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hemorragia ginecológica y obstétrica en mujeres caucásicas con deficiencia congénita de factor XI: Resultados de veinte años de registro observacional y retrospectivo" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 3505 "Ancho" => 2854 "Tamanyo" => 446231 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Graphic representation of cases with gynaecological/obstetrical bleeding episodes according to FXI:C quintiles (A–C) and ROC curves for optimal FXI:C levels cut-off selection (D–F). Abnormal uterine bleeding (A, D), postpartum haemorrhage (B, E) and postsurgical haemorrhage (C, F) showed an association with FXI:C activity, with a common FXI:C level cut-off at 43.5%. FXI: factor XI; FXI:C: FXI clotting activity; ROC: receiver-operating-characteristic.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Factor XI (FXI) is an 80-kDa glycoprotein primarily secreted by hepatocytes into plasma, where it circulates as a dimer. Following FXI activation, which is caused by FXIIa and by thrombin, FXIa participates in the contact phase and propagates coagulation response, but it also plays a role in fibrinolysis, inflammation and innate immunity.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Congenital FXI deficiency has been considered a rare bleeding disorder characterized by a decreased FXI activity in plasma due to <span class="elsevierStyleItalic">F11</span> gene mutations. Formerly called haemophilia C, it is inherited autosomally and it is expressed with a variable penetrance. Mild/moderate FXI deficiencies (FXI 20–70%) exhibit a heterozygote inheritance, whilst severe FXI deficiencies (FXI <20%) are caused by homozygous or compound heterozygous mutations.<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3–5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">FXI deficiency was first described in Ashkenazi Jewish, for whom it constitutes one of the most prevalent genetic diseases (with frequencies of 8% and 0.2% for heterozygous and homozygous gene variants, respectively), being a 98% of cases caused only by two common mutations in <span class="elsevierStyleItalic">F11</span>.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> The prevalence of FXI deficiency in Caucasians is unknown, although it was thought to be much lower (1/10,000–1/50,000 for mild/moderate and 1/1,000,000 for severe deficiencies). However, recent studies suggest that FXI deficiency might be underestimated in Caucasians.<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6,7</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Unlike haemophilia A and B, FXI deficiency affects both men and women, it debuts at any age and its benign clinical course does not resemble the classical haemophilic one, even in the case of severe FXI deficiencies. Thus, while spontaneous bleeding episodes are unusual, FXI deficient patients tend to bleed excessively after trauma or surgery, especially when highly fibrinolytic tissues are involved, such as rhino/oropharyngeal and genitourinary mucosa.<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">2,8,9</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Menstruation, pregnancy and birth labour constitute intrinsic haemostatic challenges for FXI deficient women.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a> Nevertheless, little is known about clinical management of this particularly susceptible population, especially at the obstetrical setting.<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">11,12</span></a> First, it is difficult to predict the individual risk of both gynaecological and obstetrical bleeding. Noteworthy, the clinical bleeding course is not uniform among patients with the same mutation. Even more, the risk of bleeding is not clearly related to the grade of FXI deficiency.<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">13–15</span></a> Apart from that, a myriad of limitations can restrict the conclusions of previous studies evaluating gynaecological/obstetrical bleeding in women with FXI deficiency, as their analyses are based on small-sized and heterogeneous case series, which are focused almost exclusively on Ashkenazi women (an ethnic group with a restricted genetic background). Moreover, most studies identified patients with FXI deficiency by clinical signs (bleeding), introducing clinical selection biases. Finally, neither other haemorrhagic risk factors nor the role of antihaemorrhagic measures have ever been evaluated in previous series.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The main aim of this study was to characterize gynaecological and obstetrical bleeding in a large cohort of Caucasian women with FXI deficiency, diagnosed by laboratory findings or familiar studies. A secondary objective comprised analysing the effectiveness and safety of the antihaemorrhagic treatment among this population of interest.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Materials and methods</span><p id="par0035" class="elsevierStylePara elsevierViewall">This is a retrospective observational study of a cohort of FXI deficient women collected from the city of Yecla, in the Southeast of Spain, during 20 years (1994–2014). Data regarding the <span class="elsevierStyleItalic">Yecla study</span> are described in detail elsewhere.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">4</span></a> Briefly, index cases were detected by evaluating a prolonged aPTT ratio (>1.3). Over the 20-year collecting period, 324,764 aPTT tests were performed to 51,366 patients. A prolonged aPTT ratio >1.3 was identified in 1700 subjects. Patients treated with anticoagulants or those who had a positive test for lupus anticoagulant were excluded. After dosing intrinsic coagulation factors, 44 FXI deficient cases were identified, with FXI coagulant levels (FXI:C) <70%. A family analysis of these index cases allowed the recruitment of a total of 214 individuals with FXI deficiency. A full biochemical and molecular analysis of all FXI deficient subjects was done.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Our work included all women >14 years old from the <span class="elsevierStyleItalic">Yecla study</span> cohort. General data comprised the following variables: age, sex, blood group, aPTT ratio, FXI:C, mutational status for <span class="elsevierStyleItalic">F11</span> gene as well as F2 c.*97G>A (rs1799963) and FV Leiden (rs6025) prothrombotic polymorphisms. Data were collected from medical records. Haemorrhagic events were registered by location and mechanism, including abnormal uterine bleeding (both menstrual and non-menstrual forms). A complete obstetrical record was also elaborated, which included: gravity, parity, miscarriage, mode of delivery, anaesthetic procedure, postpartum haemorrhage and whether antihaemorrhagic prophylaxis or treatment was required. Surgical interventions and postoperative bleeding were recorded, as well as the use of antihaemorrhagic prophylaxis or treatment. As a result of a long collecting period (1994–2014), neither uniform, standardized clinical definitions nor bleeding rating scales could be applied.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Statistical analysis was performed with the use of <span class="elsevierStyleItalic">Excel</span> (<span class="elsevierStyleItalic">Microsoft, USA</span>), <span class="elsevierStyleItalic">GraphPadPrism</span> (<span class="elsevierStyleItalic">GraphPad Software, USA</span>), and <span class="elsevierStyleItalic">IBM SPSS Statistics 21</span> (<span class="elsevierStyleItalic">IBM SPSS Software, USA</span>). Descriptive analysis of qualitative and quantitative variables included percentages and mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>standard deviation, respectively. <span class="elsevierStyleItalic">Pearson's Chi-Squared test</span> and <span class="elsevierStyleItalic">Fisher's Exact test</span> or <span class="elsevierStyleItalic">Linear-By-Linear</span> derivations were used for comparison of proportions or ordinal variables. <span class="elsevierStyleItalic">Kolmogorov–Smirnov</span> and <span class="elsevierStyleItalic">Shapiro–Wilk</span> tests were used for testing normality. Parametric <span class="elsevierStyleItalic">Student's-T-test</span> and non-parametric <span class="elsevierStyleItalic">Mann–Whitney U test</span> were used for comparison of two means. Apart from <span class="elsevierStyleItalic">p</span> values, 95% confidence intervals (95%CI) were also calculated. The potential association between bleeding phenotype and plasma FXI:C values was analyzed, for which our cohort was divided in quintiles of FXI:C levels. Furthermore, in order to explore an optimal FXI:C cut-off value, a <span class="elsevierStyleItalic">Receiver-Operating-Characteristic</span> (ROC) curve analysis was performed.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Ethical approval</span><p id="par0050" class="elsevierStylePara elsevierViewall">All individual participants included in the study provided written informed consent. All procedures performed were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments. The study was approved by the local ethics committee.</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Demographics, laboratory and genetics</span><p id="par0055" class="elsevierStylePara elsevierViewall">A total of 95 women out 214 subjects from 44 unrelated families had FXI deficiency, harbouring 13 different <span class="elsevierStyleItalic">F11</span> genetic variants. Demographic, laboratory and genetic data of this cohort are shown in <span class="elsevierStyleBold">Table S1</span> (<a class="elsevierStyleCrossRef" href="#sec0090">Appendix A. Supplementary data</a>). Noteworthy, only three women had a severe FXI deficiency (FXI:C levels <20%).</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">General haemorrhagic history and FXI activity</span><p id="par0060" class="elsevierStylePara elsevierViewall">Bleeding events were reported in 26 out of 95 women with FXI deficiency (27.4%), most of them as a single episode (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>16), although 7 women suffered two episodes, 2 women three episodes and one woman four episodes. Most of these 40 haemorrhagic events (21/40: 52.5%) were induced after dental, surgical or obstetrical procedures, while 19 spontaneous bleeding events were recorded (47.5%): epistaxis, cutaneous or abnormal uterine bleeding (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Firstly, the association between general haemorrhagic history and FXI deficiency was studied. FXI:C activity was significantly lower in the group of <span class="elsevierStyleItalic">bleeders</span> (subjects suffering from any bleeding episode) than in the group of <span class="elsevierStyleItalic">non-bleeders</span> (37.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>17.1% vs. 45.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10.9%, respectively; mean difference: 8.4%; 95%CI: 1.1–15.7%; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.026), probably affected by the fact that the three women with severe FXI deficiency had haemorrhagic episodes, both induced and spontaneous. Accordingly, our cohort was divided in quintiles of FXI:C (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). An asymmetric distribution of cases with bleeding episodes was observed, being more frequent in severe or nearly-severe FXI deficient quintiles (<span class="elsevierStyleItalic">linear-by-linear association</span>, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.034). Furthermore, the three women who suffered more than two haemorrhagic episodes presented a nearly-severe FXI deficiency, with FXI:C values of 22%, 26% and 36%.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Gynaecological and obstetrical haemorrhagic history</span><p id="par0070" class="elsevierStylePara elsevierViewall">Most women with bleeding events reported gynaecological or obstetrical haemorrhagic episodes, including abnormal utering bleeding, postpartum haemorrhage, excessive bleeding after a miscarriage and bleeding after gynaecological surgery: 19/26 (73.1%).</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Abnormal uterine bleeding</span><p id="par0075" class="elsevierStylePara elsevierViewall">Abnormal uterine bleeding was the most frequent type of haemorrhage by location, affecting 12 out of 95 women with FXI deficiency (12.6%) and representing 30% (12/40) of all haemorrhagic episodes of these subjects. However, no severe events were reported, as all episodes turned self-limited and no one required from hospitalization or antihaemorrhagic interventions.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Pregnancy</span><p id="par0080" class="elsevierStylePara elsevierViewall">A total of 158 pregnancies and 136 deliveries were registered from 57 women with FXI deficiency. Two of the three women with severe FXI deficiency had also been pregnant and reported four deliveries without any complication. In contrast, nine deliveries from nine women with mild/moderate FXI deficiency presented bleeding complications, which means that the proportion of postpartum haemorrhage was 6.6% (9/136). Distribution of these nine cases according to type of delivery and interventions performed are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. No women with FXI deficiency received antihaemorrhagic prophylactic agents before delivery, as their coagulopathy was unknown at that moment. On the contrary, once postpartum haemorrhages were evidenced, different therapeutic interventions were used. Red blood cell transfusion was required in four cases; fresh frozen plasma (FFP) was administered in six cases and endometrial curettages were performed in two cases. Two deliveries required more than one type of intervention.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">As regard to the type of delivery, 128 were vaginal and eight took place by caesarean. Eight out of nine postpartum haemorrhages occurred in vaginal deliveries (8/128, 6.3%) and the other one happened after a caesarean (1/8, 12.5%). No statistical significance as regard to the incidence of postpartum haemorrhage was observed between these two modes of delivery (Fisher test, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.380).</p><p id="par0090" class="elsevierStylePara elsevierViewall">Three twin pregnancies were recorded, all in women with mild/moderate FXI deficiency. No bleeding events were observed in these pregnancies and no differences were detected in this group as regard to FXI levels (data not shown).</p><p id="par0095" class="elsevierStylePara elsevierViewall">Anaesthetic procedures were applied in 56 out of 136 deliveries (41.2%). The anaesthesia used was local in 75% (42/56), epidural in 14.3% (8/56) and general in 10.7% (6/56). No antihaemorrhagic measures were administered and neither bleeding complications nor cases of epidural hematomas were registered.</p><p id="par0100" class="elsevierStylePara elsevierViewall">Fifteen out of 57 pregnant women with FXI deficiency (26.3%) reported one or more first trimester miscarriages: 12 women suffered a miscarriage and three women communicated two, three and five miscarriages. Consequently, a total of 22 early losses in 158 pregnancies (13.9%) were registered in our cohort of women with FXI deficiency. A single episode of excessive bleeding after abortion was registered. No differences in mean FXI levels were detected between women who presented an early embryofoetal loss and those who did not (45.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>17.0% vs. 43.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>13.1%, respectively; mean difference: −1.7%; 95%CI95%: −10.3–6.9%; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.691).</p><p id="par0105" class="elsevierStylePara elsevierViewall">A perinatal death (stillborn) was registered in a woman suffering from moderate FXI deficiency, who communicated two additional non-complicated gestations.</p><p id="par0110" class="elsevierStylePara elsevierViewall">No maternal deaths occurred in our cohort.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Gynaecological surgery</span><p id="par0115" class="elsevierStylePara elsevierViewall">A total of 25 gynaecological surgeries were recorded in 20 women with FXI deficiency. The coagulopathy had already been diagnosed at the time of surgery in some subjects and, based on clinical haematologist decision, antihaemorrhagic prophylaxis (FFP) was provided to 12 out of 25 procedures (48%) in 12 out of 20 women (60%). Types of intervention, postoperative bleeding complications and antihaemorrhagic measures are described in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>.</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">Four postoperative haemorrhages were registered in four different women, occurring after two hysterectomies and after the intervention of a Bartholin's cyst and a haemorrhagic follicle. This supposes an incidence of gynaecological postoperative bleeding of 16% of the procedures (4/25) and 20% of the women (4/20).</p><p id="par0125" class="elsevierStylePara elsevierViewall">Noteworthy, all but one of the affected individuals had received prophylactic antihaemorrhagic agents. Thus, the incidence of postoperative bleeding was elevated in our cohort independently of the prophylaxis: three out of 12 women with prophylaxis suffered from bleeding (25%) while only one out of eight with no prophylaxis bled after gynaecological surgery (12.5%). However, it is important to point out that women who were administered prophylactic agents had presented more haemorrhagic episodes than women who had not (33% vs. 12.5%, respectively) and had significantly lower FXI:C levels (34.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>13% vs. 48.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>6.4%, respectively; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.004).</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Complications due to antihaemorrhagic systemic treatments</span><p id="par0130" class="elsevierStylePara elsevierViewall">Different antihaemorrhagic systemic measures were administered with a prophylactic intention in 12 gynaecological surgeries and with a therapeutic intention in six postpartum haemorrhages. They consisted of FFP administration, supplemented in one case with tranexamic acid. FXI concentrate was not used in our cohort. While the effectiveness of prophylactic FFP might be questioned, as six out of 18 procedures still reported bleedings (33.3%), we point out two severe complications secondary to its use (11.8%): an allergic reaction and a transfusion related acute lung injury (TRALI) requiring Intensive Care Unit (ICU) admission for orotracheal intubation, mechanical ventilation and treatment with vasoactive drugs, with favourable evolution.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Analysis of gynaecological/obstetrical haemorrhagic risk</span><p id="par0135" class="elsevierStylePara elsevierViewall">A positive history of bleeding and low FXI:C values significantly increased the risk of three gynaecological/obstetrical bleedings: abnormal uterine bleeding, postpartum haemorrhage and gynaecological postoperative haemorrhage (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0140" class="elsevierStylePara elsevierViewall">Regarding FXI:C levels, an asymmetric distribution of gynaecological/obstetrical bleeding episodes was observed (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A–C), being more frequent in severe or nearly-severe FXI deficient quintiles (<span class="elsevierStyleItalic">linear-by-linear association</span>: <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.007, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.017 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.112 for abnormal uterine bleeding, postpartum and gynaecological postoperative haemorrhage, respectively).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">Finally, ROC curve analysis was performed (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>D–F). As a measure of FXI:C levels accuracy, the area under the curve (AUC) was calculated for each gynaecological/obstetrical haemorrhage and FXI:C activity rendered a significant discrimination power (abnormal uterine bleeding: AUC<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.75, 95%CI: 0.62–0.88, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.006; postpartum haemorrhage: AUC<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.76, 95%CI: 0.63–0.90, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.013; postoperative haemorrhage: AUC<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.82, 95%CI: 0.60–1.00, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.047). Moreover, a common FXI:C level cut-off at 43.5% was identified for these three gynaecological/obstetrical haemorrhages, rendering a global sensitivity of 85% and a global specificity of 60%.</p><p id="par0150" class="elsevierStylePara elsevierViewall">In order to perform a sensitivity analysis, we repeated all of the previously mentioned statistics excluding the 3 subjects with severe deficiency. Interestingly, abnormal uterine bleeding, postpartum and gynaecological postoperative haemorrhages were still associated to a positive history of bleeding, whilst only abnormal uterine bleeding and postpartum haemorrhage were more frequent in women from the lowest FXI:C quintiles. Postsurgical bleeding did not consistently show this association, but two out of three gynaecological postsurgical events also occurred in women from the lowest FXI:C quintiles.</p><p id="par0155" class="elsevierStylePara elsevierViewall">Other potential factors that could modulate the haemorrhagic risk in FXI deficient women were evaluated in this study: ABO and Rh blood groups, and prothrombotic polymorphisms (rs1799963, rs6025). However, none of these factors played a significant role on the risk of gynaecological/obstetrical bleeding in women with FXI deficiency (data not shown).</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Discussion</span><p id="par0160" class="elsevierStylePara elsevierViewall">Haemorrhagic events among subjects with FXI deficiency are rare and usually not serious, but they might also be fatal.<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">2,16</span></a> Unfortunately, no predictor markers of the haemorrhagic risk have been reported.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a> Genitourinary mucosa is a well-known fibrinolytic tissue, associated to a higher bleeding tendency in women with FXI deficiency. Thus, clinical management of gynaecological/obstetrical bleeding in such a susceptible population generates anxiety to gynaecologists, anaesthesiologists and haematologists.</p><p id="par0165" class="elsevierStylePara elsevierViewall">A recent systematic review, which comprises 372 FXI deficient women from a total of 27 different studies, summarizes current evidence.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">18</span></a> This study concludes that affected women present higher risks of abnormal uterine bleeding, postpartum and gynaecological postoperative haemorrhage than general population, with frequencies near 20% and similar to those of women suffering from von Willebrand disease.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a> Despite of a reasonable sample size, this review is based on different, heterogeneous studies suffering from clinical selection bias. Moreover, this study includes many women of a specific ethnic group, with high degree of consanguinity and, therefore, with a very uniform genetic background.</p><p id="par0170" class="elsevierStylePara elsevierViewall">Our study, conducted in a large, single-centre cohort, overcomes many of the previously mentioned handicaps and provides interesting information on the risk of gynaecological and obstetrical bleeding in Caucasian women with FXI deficiency. First, enrolled subjects were selected according to non-clinical criteria, such as analytical and family studies. Actually, most of the cases included in our work were exposed to different bleeding risk conditions without a previous diagnosis of FXI deficiency and, therefore, they did not receive prophylactic interventions and overtreatment that could mask the effect of FXI deficiency. Other strength of our study is the genetic heterogeneity of our cohort, with 13 different mutations underlying FXI deficiency. Finally, our study mostly includes women with mild/moderate FXI deficiency (92 cases), a disorder that according to recent evidences may be much more prevalent than thought, also in the Caucasian population, because of its subclinical course, its molecular variability and the lack of accurate screening techniques.<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">13,17,20</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Our cohort comprised a total of 95 women with FXI deficiency, reporting information about 158 gestations, 136 deliveries and 25 gynaecological interventions. Unfortunately, as a result of a long collecting period (1994–2014), neither uniform, standardized clinical definitions nor bleeding rating scales could be applied.</p><p id="par0180" class="elsevierStylePara elsevierViewall">Our results showed a noticeable proportion of abnormal uterine bleeding (12.6%), postpartum haemorrhage (6.6%) and gynaecological postoperative haemorrhage (16%), higher than that observed in general population, but markedly lower than that reported in other series and systematic reviews.<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">18,21,22</span></a> Furthermore, clinical severity was mild/moderate in most of our cases, especially when excessive menstrual bleeding is considered. A more benign bleeding phenotype in our cohort, in terms of incidence and severity, could be explained by the fact that the design of our study prevents clinical selection bias and, so that, reflects a broader spectrum of FXI deficient subjects.</p><p id="par0185" class="elsevierStylePara elsevierViewall">In our study, a positive history of bleeding and low plasmatic FXI levels (FXI:C ≤43.5%) were associated with a higher prevalence of gynaecological/obstetrical bleeding. Previous series support a <span class="elsevierStyleItalic">bleeder</span> phenotype as a strong risk factor.<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">17,21</span></a> However, poor correlation between FXI levels and the occurrence of haemorrhagic episodes has been pointed in previous works.<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">15,17</span></a> Further studies are required to clarify whether the levels of FXI associate with bleeding.</p><p id="par0190" class="elsevierStylePara elsevierViewall">Many clinicians are reluctant to the use of locoregional anaesthesia in women with coagulopathies, due to the risk of presenting an epidural haematoma causing acute spinal cord compression.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a> However, current evidence encourages to using epidural anaesthesia in FXI deficient women, especially in the case of <span class="elsevierStyleItalic">non-bleeder</span> phenotype or moderate deficiencies.<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">11,18</span></a> Our data support this suggestion as neither bleeding complications nor cases of epidural hematomas were registered in six women who received epidural anaesthesia without antihaemorrhagic prophylaxis.</p><p id="par0195" class="elsevierStylePara elsevierViewall">Both postpartum and gynaecological postoperative bleeding are issues that comprise clinicians, particularly at the antepartum and preoperative phases. Whether an expectant or a prophylactic attitude should be adopted is one of the first and most important decisions to make.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a> Current guidelines suggest antihaemorrhagic prophylaxis in FXI deficient women, particularly in cases of positive bleeding history or severe deficiency. Actually, some studies recommend systematic prophylaxis, ensuring fewer complications, although they are only based on high-risk patients.<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">13,17,21,25</span></a> Thus, a benefit/risk rationale is required in such an uncertain clinical scenario. Our work also provides new information concerning antihaemorrhagic prophylaxis in women with FXI deficiency. Due to the design of our study, as FXI deficiency was unknown at the time of all deliveries and most of the surgeries, systemic agents such as FFP were just administered prior 12 out of 25 gynaecological procedures. As regard their effectiveness (benefit), it might be questioned by the fact that 3 out of 12 patients with FFP pre-treatment bled (25%), a proportion higher to that found in interventions with no prophylaxis (7.7%). Although potential biases should be considered, it is also well known that the effect of FFP in FXI:C activity is erratic and unpredictable. However, on the other side, we should take in mind the harmful consequences (risks) of antihaemorrhagic overtreatment, such as allergic reactions, TRALI, thrombosis or disseminated intravascular coagulation.<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">2,26</span></a> In fact, in our cohort, two out of 12 women to whom FFP was administered showed severe side effects (16.7%), consisting of an allergic reaction and a TRALI requiring ICU admission. Although further studies are required, taking into account the mild bleeding phenotype associated to FXI deficiency, the uncertain efficacy of FFP and its potentially devastating side effects, the recommendation of systematic antihaemorrhagic prophylaxis in women with FXI deficiency should be questioned. As our analysis suggests that a positive history of haemorrhage and FXI:C levels ≤43.5% might increase the risk of both postpartum or postsurgical bleeding, prophylactic measures that achieve upper FXI levels might be explored in this subset of patients.</p><p id="par0200" class="elsevierStylePara elsevierViewall">Unfortunately, our study did not identify any new factor modulating the risk of bleeding among patients with FXI deficiency. Thus, the O blood group, previously suggested increasing the risk of postpartum haemorrhage due to lower levels of von Willebrand factor,<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">22,27</span></a> plays no significant role in our cohort. On the opposite way, the prothrombotic polymorphisms that could protect against bleeding episodes (rs1799963, rs6025)<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">28,29</span></a> did not reduce the risk of gynaecological/obstetrical bleeding in subjects with FXI deficiency.</p><p id="par0205" class="elsevierStylePara elsevierViewall">Finally, the rate of embryofoetal losses described in our cohort (22 out of 158 pregnancies, 13.9%), was similar to that reported in previous studies<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">11,22,23</span></a> and comparable to the rate of first trimester miscarriage known for the general population.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a> All these data sustain that FXI deficiency does not increase the risk of abortion.</p><p id="par0210" class="elsevierStylePara elsevierViewall">Our work possesses various limitations, which are basically connected to its design as a retrospective, observational study of data collected during a wide temporary period of 20 years. Clinical registry included both general and gynaecological/obstetrical information. As previously mentioned, no standard definitions nor validated rating scales for bleeding could be applied. However, these problems are almost constant in similar series. Future studies should be based on large-sized, multicentre, prospective cohorts and share homogeneous criteria. Gynaecologists, anaesthesiologists and haematologists should be implied in the development of these eventual studies.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Author contribution</span><p id="par0215" class="elsevierStylePara elsevierViewall">VV and JC designed the research. CB-P, TR, JE and MEM-B analyzed the clinical and biochemical data. JE provided study materials from patients and collected clinical information. MEM-B, SS-A, AM and BM-B performed genetic functional and biochemical analysis, CB-P and JC wrote the paper. VV, MEM-B and JE revised the manuscript.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Funding</span><p id="par0220" class="elsevierStylePara elsevierViewall">This work was supported by PI15/00079 & CB15/00055 (ISCIII and FEDER); Fundación Española de Trombosis y Hemostasia, and 19873/GERM/15 (Fundación Séneca). MEM holds a fellowship from Fundación Española de Trombosis y Hemostasia, Spain. SS-A holds a fellowship from Sociedad Española de Hematología y Hemoterapia, Spain.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Conflicts of interest</span><p id="par0225" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres1263682" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Material and methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1169995" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xpalclavsec1169996" "titulo" => "Abbreviations" ] 3 => array:3 [ "identificador" => "xres1263683" "titulo" => "Resumen" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Material y métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusión" ] ] ] 4 => array:2 [ "identificador" => "xpalclavsec1169997" "titulo" => "Palabras clave" ] 5 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 6 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Ethical approval" ] ] ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Results" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Demographics, laboratory and genetics" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "General haemorrhagic history and FXI activity" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Gynaecological and obstetrical haemorrhagic history" ] 3 => array:2 [ "identificador" => "sec0040" "titulo" => "Abnormal uterine bleeding" ] 4 => array:2 [ "identificador" => "sec0045" "titulo" => "Pregnancy" ] 5 => array:2 [ "identificador" => "sec0050" "titulo" => "Gynaecological surgery" ] 6 => array:2 [ "identificador" => "sec0055" "titulo" => "Complications due to antihaemorrhagic systemic treatments" ] 7 => array:2 [ "identificador" => "sec0060" "titulo" => "Analysis of gynaecological/obstetrical haemorrhagic risk" ] ] ] 8 => array:2 [ "identificador" => "sec0065" "titulo" => "Discussion" ] 9 => array:2 [ "identificador" => "sec0070" "titulo" => "Author contribution" ] 10 => array:2 [ "identificador" => "sec0075" "titulo" => "Funding" ] 11 => array:2 [ "identificador" => "sec0080" "titulo" => "Conflicts of interest" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-07-16" "fechaAceptado" => "2019-01-31" "PalabrasClave" => array:2 [ "en" => array:2 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1169995" "palabras" => array:6 [ 0 => "Factor XI deficiency" 1 => "Mutation spectrum" 2 => "Bleeding symptoms" 3 => "Gynaecological bleeding" 4 => "Obstetrical bleeding" 5 => "Surgical procedures" ] ] 1 => array:4 [ "clase" => "abr" "titulo" => "Abbreviations" "identificador" => "xpalclavsec1169996" "palabras" => array:10 [ 0 => "aPTT" 1 => "AUC" 2 => "CI" 3 => "F11" 4 => "FFP" 5 => "FXI" 6 => "FXI:C" 7 => "ICU" 8 => "ROC" 9 => "TRALI" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1169997" "palabras" => array:6 [ 0 => "Deficiencia de factor XI" 1 => "Espectro mutacional" 2 => "Clínica hemorrágica" 3 => "Hemorragia ginecológica" 4 => "Hemorragia obstétrica" 5 => "Procedimientos quirúrgicos" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Factor XI (FXI) deficiency is a mild bleeding disorder, common among Ashkenazis, that may be underestimated in Caucasians. Management of FXI deficiency in women is a challenge, due to its unpredictable bleeding tendency and the little evidence available on this issue.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To describe gynaecological/obstetrical bleeding complications and to analyze the effectiveness and safety of the antihaemorrhagic treatment among women with FXI deficiency.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Material and methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A retrospective, observational study of 214 Caucasian subjects with FXI deficiency collected during 20 years (1994–2014) without clinical selection.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">We identified 95 women with FXI deficiency. Any haemorrhagic event was communicated by 26/95 (27.4%), being abnormal uterine bleeding the most frequently found (12/95, 12.6%). Nine postpartum haemorrhages were recorded from 136 deliveries (6.6%) in 57 women. Four postsurgical bleeding complications were registered among 25 gynaecological surgeries (16%) in 20 women. Abnormal uterine bleeding, postpartum and postsurgical haemorrhages were related to both a positive bleeding history and FXI:C values ≤43.5%. Prophylaxis with fresh frozen plasma, used in 12/25 (48%) gynaecological surgeries, did not prevent from postoperative bleeding in three cases, but two developed severe adverse reactions.</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Women with FXI deficiency, especially those with a positive history of bleeding or FXI:C ≤43.5%, are at risk of developing gynaecological/obstetrical haemorrhages, most of them mild/moderate. Systematic prophylaxis has questionable effectiveness, but might cause severe side effects.</p></span>" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Material and methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducción</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">La deficiencia del factor XI (FXI) es un trastorno hemorrágico leve, común entre los asquenazíes, que puede subestimarse en los caucásicos. El manejo de la deficiencia de FXI en las mujeres es un desafío, debido a la dificultad para predecir la tendencia hemorrágica y la poca evidencia disponible sobre este tema.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivo</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Describir las complicaciones hemorrágicas ginecológicas/obstétricas y analizar la efectividad y la seguridad del tratamiento antihemorrágico en mujeres con deficiencia de FXI.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Material y métodos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Estudio observacional retrospectivo de 214 sujetos caucásicos con deficiencia de FXI recogidos durante 20 años (1994-2014) sin selección clínica.</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Se identificaron 95 mujeres con deficiencia de FXI. Cualquier evento hemorrágico fue comunicado por 26/95 (27.4%), siendo la hemorragia uterina anormal el más frecuente (12/95, 12.6%). Se registraron nueve hemorragias posparto de 136 partos (6,6%) en 57 mujeres. Se registraron cuatro complicaciones hemorrágicas posquirúrgicas en 25 cirugías ginecológicas (16%) en 20 mujeres. La hemorragia uterina anormal y las hemorragias postparto y posquirúrgicas se relacionaron con una historia positiva para hemorragia y valores de FXI:C ≤ 43.5%. La profilaxis con plasma fresco congelado, utilizado en 12/25 (48%) cirugías ginecológicas, no evitó la hemorragia postoperatoria en tres casos, pero dos desarrollaron reacciones adversas graves.</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusión</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Las mujeres con deficiencia de FXI, especialmente aquellas con una historia positiva para hemorragia o FXI:C ≤ 43.5%, están en riesgo de desarrollar hemorragias ginecológicas/obstétricas, la mayoría de ellas leves/moderadas. La profilaxis sistemática tiene una efectividad cuestionable, pero puede causar efectos secundarios graves.</p></span>" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Material y métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusión" ] ] ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0235" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0090" ] ] ] ] "multimedia" => array:7 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 971 "Ancho" => 1517 "Tamanyo" => 68127 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Graphic representation of cases with bleeding episodes according to FXI:C quintiles. Our cohort was divided in quintiles of FXI:C. An asymmetric distribution of cases with bleeding episodes was observed, being more frequent in severe or nearly-severe quintiles (<span class="elsevierStyleItalic">linear-by-linear association</span>, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.034). FXI: factor XI; FXI:C: FXI clotting activity.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 3505 "Ancho" => 2854 "Tamanyo" => 446231 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Graphic representation of cases with gynaecological/obstetrical bleeding episodes according to FXI:C quintiles (A–C) and ROC curves for optimal FXI:C levels cut-off selection (D–F). Abnormal uterine bleeding (A, D), postpartum haemorrhage (B, E) and postsurgical haemorrhage (C, F) showed an association with FXI:C activity, with a common FXI:C level cut-off at 43.5%. FXI: factor XI; FXI:C: FXI clotting activity; ROC: receiver-operating-characteristic.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">FXI: factor XI.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Type of haemorrhage \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Number of episodes \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Proportion (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">Induced</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Dental procedure</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Surgery</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Postpartum haemorrhage</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Abortion</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">Spontaneous</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">47.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Epistaxis</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Cutaneous</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Abnormal uterine bleeding</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">Gynaecological or obstetrical bleeding</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">65 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">Total</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2161455.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">All postoperative haemorrhages occurred after a gynaecological procedure.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Gynaecological or obstetrical bleeding: includes abnormal uterine bleeding, postpartum, post-abortion and postoperative haemorrhages.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Haemorrhagic episodes by mechanism and location.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">FXI: factor XI; FFP: fresh frozen plasma.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Type of delivery \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Number of deliveries \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Postpartum haemorrhage, number (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Intervention</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Blood \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FFP \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Curettage \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vaginal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">128 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (6.3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Caesarean \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (12.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">136 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (6.6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2161458.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Type of delivery, postpartum haemorrhage and interventions.</p>" ] ] 4 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">FFP: fresh frozen plasma; Trnx: tranexamic acid; TRALI: transfusion related acute lung injury.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Type of surgery \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Number of procedures \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Prophylaxis \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Postsurgical haemorrhages \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FFP-related severe adverse reaction \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hysterectomy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FFP: 3; FFP<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>Trnx: 1<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 allergic reaction; 1 TRALI \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Adnexectomy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FFP: 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ovarian cyst \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FFP: 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Haemorrhagic follicle \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FFP<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Endometrial curettage \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FFP: 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Uterine abnormality \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FFP: 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tubal ligation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Conization \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FFP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bartholin's cyst \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FFP<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cystocele repair \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2161457.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Prophylactic measures that failed in preventing gynaecological postoperative bleeding.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Gynaecological surgeries, postoperative bleeding and interventions.</p>" ] ] 5 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">FXI: factor XI; FXI:C: FXI clotting activity; Mean diff, mean difference; 95%CI: 95% confidence interval.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Abnormal uterine bleeding</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Postpartum haemorrhage</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Postsurgical haemorrhage</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Bleeders \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Non-bleeders \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Bleeders \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Non-bleeders \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Bleeders \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Non-bleeders \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">History of diff. bleeding (%)<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">31.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">p</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.028</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.011</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.032</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FXI:C (mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>15.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">35.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>17.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">43.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>9.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean diff. 95%CI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.4–20.9</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.2–20.1</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.2–30.2</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">p</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.001</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.047</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.012</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2161456.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0020">History of a different bleeding: for each gynaecological/obstetrical haemorrhage, <span class="elsevierStyleItalic">bleeders</span> and <span class="elsevierStyleItalic">non-bleeders</span> categories were generated, including any haemorrhagic episode except the one that was being analyzed in that case (abnormal uterine bleeding, postpartum haemorrhage and postsurgical haemorrhage, respectively).</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">History of bleeding and FXI:C values in bleeders and non-bleeders of three gynaecological haemorrhages identified among women with FXI deficiency.</p>" ] ] 6 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.pdf" "ficheroTamanyo" => 87932 ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0155" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Contact system revisited: an interface between inflammation, coagulation, and innate immunity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A.T. Long" 1 => "E. Kenne" 2 => "R. Jung" 3 => "T.A. Fuchs" 4 => "T. Renne" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Thromb Haemost" "fecha" => "2016" "volumen" => "14" "paginaInicial" => "427" "paginaFinal" => "437" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0160" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Why factor XI deficiency is a clinical concern" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A.P. Wheeler" 1 => "D. Gailani" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/17474086.2016.1191944" "Revista" => array:7 [ "tituloSerie" => "Expert Rev Hematol" "fecha" => "2016" "volumen" => "9" "paginaInicial" => "629" "paginaFinal" => "637" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27216469" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0954611112003125" "estado" => "S300" "issn" => "09546111" ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0165" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Factor XI deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "S. Duga" 1 => "O. Salomon" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1055/s-0029-1225764" "Revista" => array:6 [ "tituloSerie" => "Semin Thromb Hemost" "fecha" => "2009" "volumen" => "35" "paginaInicial" => "416" "paginaFinal" => "425" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19598070" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0170" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "High incidence of FXI deficiency in a Spanish town caused by 11 different mutations and the first duplication of F11 results from the Yecla study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Esteban" 1 => "M.E. de la Morena-Barrio" 2 => "S. Salloum-Asfar" 3 => "J. Padilla" 4 => "A. Miñano" 5 => "V. Roldán" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/hae.13356" "Revista" => array:6 [ "tituloSerie" => "Haemophilia" "fecha" => "2017" "volumen" => "23" "paginaInicial" => "e488" "paginaFinal" => "e496" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28960694" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0175" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "New hemophilia-like disease caused by deficiency of a third plasma thromboplastin factor" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "R.L. Rosenthal" 1 => "O.H. Dreskin" 2 => "N. Rosenthal" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Proc Soc Exp Biol Med" "fecha" => "1953" "volumen" => "82" "paginaInicial" => "171" "paginaFinal" => "174" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0180" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Exploring the global landscape of genetic variation in coagulation factor XI deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Asselta" 1 => "E.M. Paraboschi" 2 => "V. Rimoldi" 3 => "M. Menegatti" 4 => "F. Peyvandi" 5 => "O. Salomon" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2017-04-780148" "Revista" => array:7 [ "tituloSerie" => "Blood" "fecha" => "2017" "volumen" => "130" "paginaInicial" => "e1" "paginaFinal" => "e6" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28615222" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0954611112000261" "estado" => "S300" "issn" => "09546111" ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0185" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Factor XI deficiency in humans" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "U. Seligsohn" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1538-7836.2009.03395.x" "Revista" => array:7 [ "tituloSerie" => "J Thromb Haemost" "fecha" => "2009" "volumen" => "7" "numero" => "Suppl" "paginaInicial" => "84" "paginaFinal" => "87" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19630775" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0190" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Factor XI deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "K. Gomez" 1 => "P. Bolton-Maggs" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2516.2008.01667.x" "Revista" => array:6 [ "tituloSerie" => "Haemophilia" "fecha" => "2008" "volumen" => "14" "paginaInicial" => "1183" "paginaFinal" => "1189" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18312365" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0195" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inherited deficiencies of coagulation factors II, V, VII XI and XIII and the combined deficiencies of factors V and VIII and of the vitamin K-dependent factors" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "U. Seligshon" 1 => "A. Zivelin" 2 => "O. Salomon" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:6 [ "editores" => "M.Lichtman, T.J.Kipps, U.Seligshon, K.Kaushansky, J.T.Prchal" "titulo" => "Williams Hematology" "paginaInicial" => "1617" "paginaFinal" => "1638" "edicion" => "8th ed." "serieFecha" => "2010" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0200" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The prevalence of underlying bleeding disorders in patients with heavy menstrual bleeding with and without gynecologic abnormalities" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "H.M. Knol" 1 => "A.B. Mulder" 2 => "D.H. Bogchelman" 3 => "H.C. Kluin-Nelemans" 4 => "A.G. van der Zee" 5 => "K. Meijer" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Am J Obstet Gynecol" "fecha" => "2013" "volumen" => "209" "paginaInicial" => "202e1" "paginaFinal" => "e2027" ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0205" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Obstetric analgesia and anaesthesia in women with inherited bleeding disorders" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "C. Chi" 1 => "C.A. Lee" 2 => "A. England" 3 => "J. Hingorani" 4 => "J. Paintsil" 5 => "R.A. Kadir" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Thromb Haemost" "fecha" => "2009" "volumen" => "101" "paginaInicial" => "1104" "paginaFinal" => "1111" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19492155" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0210" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Factor XI deficiency in women" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "R.A. Kadir" 1 => "D.L. Economides" 2 => "C.A. Lee" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/(sici)1096-8652(199901)60:1<48::aid-ajh8>3.0.co;2-q" "Revista" => array:6 [ "tituloSerie" => "Am J Hematol" "fecha" => "1999" "volumen" => "60" "paginaInicial" => "48" "paginaFinal" => "54" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9883805" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0215" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Factor XI deficiency – resolving the enigma?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "P.H. Bolton-Maggs" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Hematology Am Soc Hematol Educ Program" "fecha" => "2009" "paginaInicial" => "97" "paginaFinal" => "105" ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0220" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European Network of Rare Bleeding Disorders" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "European Network of Rare Bleeding Disorders Group" "etal" => true "autores" => array:6 [ 0 => "F. Peyvandi" 1 => "R. Palla" 2 => "M. Menegatti" 3 => "S.M. Siboni" 4 => "S. Halimeh" 5 => "B. Faeser" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1538-7836.2012.04653.x" "Revista" => array:6 [ "tituloSerie" => "J Thromb Haemost" "fecha" => "2012" "volumen" => "10" "paginaInicial" => "615" "paginaFinal" => "621" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22321862" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0225" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sample conditions determine the ability of thrombin generation parameters to identify bleeding phenotype in FXI deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "G.N. Pike" 1 => "A.M. Cumming" 2 => "C.R.M. Hay" 3 => "P.H. Bolton-Maggs" 4 => "J. Burthem" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2014-12-616565" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2015" "volumen" => "126" "paginaInicial" => "397" "paginaFinal" => "405" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25911238" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0230" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acquired factor XI inhibitor presenting as spontaneous bilateral subdural hematoma in an elderly patient" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "N. Vazzana" 1 => "L. Scarti" 2 => "C. Beltrame" 3 => "A. Picchi" 4 => "G. Taccetti" 5 => "A. Fortini" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1155/2014/626831" "Revista" => array:5 [ "tituloSerie" => "Case Rep Hematol" "fecha" => "2014" "volumen" => "2014" "paginaInicial" => "626831" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25431698" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0235" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Bleeding phenotype and correlation with factor XI (FXI) activity in congenital FXI deficiency: results of a retrospective study from a single centre" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Santoro" 1 => "R. Di Mauro" 2 => "E. Baldacci" 3 => "F. De Angelis" 4 => "R. Abbruzzese" 5 => "F. Barone" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/hae.12628" "Revista" => array:6 [ "tituloSerie" => "Haemophilia" "fecha" => "2015" "volumen" => "21" "paginaInicial" => "496" "paginaFinal" => "501" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25623511" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0240" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Gynaecological and obstetrical bleeding in women with factor XI deficiency – a systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S. Wiewel-Verschueren" 1 => "I.J. Arendz" 2 => "H.M. Knol" 3 => "K. Meijer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/hae.12856" "Revista" => array:6 [ "tituloSerie" => "Haemophilia" "fecha" => "2016" "volumen" => "22" "paginaInicial" => "188" "paginaFinal" => "195" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26634881" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0245" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Gynaecological and obstetric bleeding in moderate and severe von Willebrand disease" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "Win study group" "etal" => true "autores" => array:6 [ 0 => "E.M. De Wee" 1 => "H.M. Knol" 2 => "E.P. Mauser-Bunschoten" 3 => "J.G. van der Bom" 4 => "J.C. Eikenboom" 5 => "K. Fijnvandraat" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1160/TH11-03-0180" "Revista" => array:6 [ "tituloSerie" => "Thromb Haemost" "fecha" => "2011" "volumen" => "106" "paginaInicial" => "885" "paginaFinal" => "892" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21947221" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0250" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Assessment of two contact activation reagents for the diagnosis of congenital factor XI deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Salloum-Asfar" 1 => "M.E. de la Morena-Barrio" 2 => "J. Esteban" 3 => "A. Miñano" 4 => "C. Aroca" 5 => "V. Vicente" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Thromb Res" "fecha" => "2018" "volumen" => "163" "paginaInicial" => "64" "paginaFinal" => "70" ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0255" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Variations in the incidence of postpartum hemorrhage across hospitals in California" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.C. Lu" 1 => "M. Fridman" 2 => "L.M. Korst" 3 => "K.D. Gregory" 4 => "C. Reyes" 5 => "C.J. Hobel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10995-005-0009-3" "Revista" => array:6 [ "tituloSerie" => "Matern Child Health J" "fecha" => "2005" "volumen" => "9" "paginaInicial" => "297" "paginaFinal" => "306" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16132205" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0260" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pregnancy outcome in Factor XI deficiency: incidence of miscarriage, antenatal and postnatal haemorrhage in 33 women with Factor XI deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "B. Myers" 1 => "S. Pavord" 2 => "L. Kean" 3 => "M. Hill" 4 => "G. Dolan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1471-0528.2007.01296.x" "Revista" => array:6 [ "tituloSerie" => "BJOG" "fecha" => "2007" "volumen" => "114" "paginaInicial" => "643" "paginaFinal" => "646" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17439571" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0265" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The management of factor XI deficiency in pregnancy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J. Davies" 1 => "R. Kadir" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1055/s-0036-1587685" "Revista" => array:6 [ "tituloSerie" => "Semin Thromb Hemost" "fecha" => "2016" "volumen" => "42" "paginaInicial" => "732" "paginaFinal" => "740" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27699729" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0270" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Factor XI deficiency: a description of 34 cases and literature review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "R. Santoro" 1 => "S. Prejanó" 2 => "P. Iannaccaro" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Blood Coagul Fibrinolysis" "fecha" => "2011" "volumen" => "22" "paginaInicial" => "431" "paginaFinal" => "435" ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0275" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The obstetric and gynaecological management of women with inherited bleeding disorders – review with guidelines produced by a taskforce of UK Haemophilia Centre Doctors’ Organization" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "UK Haemophilia Centre Doctor's Organization" "etal" => true "autores" => array:6 [ 0 => "C.A. Lee" 1 => "C. Chi" 2 => "S.R. Pavord" 3 => "P. Bolton-Maggs" 4 => "D. Pollard" 5 => "A. Hinchcliffe-Wood" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2516.2006.01314.x" "Revista" => array:6 [ "tituloSerie" => "Haemophilia" "fecha" => "2006" "volumen" => "12" "paginaInicial" => "301" "paginaFinal" => "336" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16834731" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0280" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acute lung injury complicating blood transfusion in post-partum hemorrhage: incidence and risk factors" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. Teofili" 1 => "M. Bianchi" 2 => "B.A. Zanfini" 3 => "S. Catarci" 4 => "R. Sicuranza" 5 => "S. Spartano" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4084/MJHID.2014.069" "Revista" => array:5 [ "tituloSerie" => "Mediterr J Hematol Infect Dis" "fecha" => "2014" "volumen" => "6" "paginaInicial" => "e2014069" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25408855" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0285" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The effect of ABO blood group on the diagnosis of von Willebrand disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J.C. Gill" 1 => "J. Endres-Brooks" 2 => "P.J. Bauer" 3 => "W.J. Marks Jr." 4 => "R.R. Montgomery" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "1987" "volumen" => "69" "paginaInicial" => "1691" "paginaFinal" => "1695" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3495304" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0290" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Polymorphisms of clotting factors modify the risk for primary intracranial hemorrhage" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J. Corral" 1 => "J.A. Iniesta" 2 => "R. Gonzalez-Conejero" 3 => "M. Villalon" 4 => "V. Vicente" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Blood" "fecha" => "2001" "volumen" => "97" "paginaInicial" => "2979" "paginaFinal" => "2982" ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0295" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: a systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.B. Segal" 1 => "D.J. Brotman" 2 => "A.J. Necochea" 3 => "A. Emadi" 4 => "L. Samal" 5 => "L.M. Wilson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "JAMA" "fecha" => "2009" "volumen" => "301" "paginaInicial" => "2472" "paginaFinal" => "2485" ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0300" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Consecutive repeat miscarriages are likely to occur in the same gestational period" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J. Yan" 1 => "S.H. Saravelos" 2 => "N. Ma" 3 => "C. Ma" 4 => "Z.J. Chen" 5 => "T.C. Li" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.rbmo.2012.03.003" "Revista" => array:6 [ "tituloSerie" => "Reprod Biomed Online" "fecha" => "2012" "volumen" => "24" "paginaInicial" => "634" "paginaFinal" => "638" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22503267" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/00257753/0000015300000010/v1_201911090636/S002577531930123X/v1_201911090636/en/main.assets" "Apartado" => array:4 [ "identificador" => "66429" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Originales" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/00257753/0000015300000010/v1_201911090636/S002577531930123X/v1_201911090636/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S002577531930123X?idApp=UINPBA00004N" ]
Información de la revista
Compartir
Descargar PDF
Más opciones de artículo
Original article
Gynaecological and obstetrical bleeding in Caucasian women with congenital factor XI deficiency: Results from a twenty-year, retrospective, observational study
Hemorragia ginecológica y obstétrica en mujeres caucásicas con deficiencia congénita de factor XI: Resultados de veinte años de registro observacional y retrospectivo
Carlos Bravo-Perez, Teresa Ródenas, Julio Esteban, Maria Eugenia de la Morena-Barrio, Salam Salloum-Asfar, Belen de la Morena-Barrio, Antonia Miñano, Vicente Vicente
, Javier Corral
Autor para correspondencia
Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Murcia, CIBERER, Spain
Artículo
This article is available in English
Gynaecological and obstetrical bleeding in Caucasian women with congenital factor XI deficiency: Results from a twenty-year, retrospective, observational study
Carlos Bravo-Perez, Teresa Ródenas, Julio Esteban, Maria Eugenia de la Morena-Barrio, Salam Salloum-Asfar, Belen de la Morena-Barrio, Antonia Miñano, Vicente Vicente, Javier Corral
10.1016/j.medcle.2019.01.042Med Clin. 2019;153:373-9