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Relevance of early diagnosis in polycythemia vera and essential thrombocythemia: A single center’s experience
Importancia del diagnóstico precoz en policitemia vera y trombocitemia esencial. Experiencia de un centro
S. Lakhwani
, M. Pardina-Echevarría, R. Arcas-Vega, O.R. Díaz-Sánchez, M.T. Hernández-García, J.M. Raya
Corresponding author
Servicio de Hematología y Hemoterapia, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain
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Lakhwani, M. Pardina-Echevarría, R. Arcas-Vega, O.R. Díaz-Sánchez, M.T. Hernández-García, J.M. Raya" "autores" => array:6 [ 0 => array:4 [ "nombre" => "S." "apellidos" => "Lakhwani" "email" => array:1 [ 0 => "sunillakhwani@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Pardina-Echevarría" ] 2 => array:2 [ "nombre" => "R." "apellidos" => "Arcas-Vega" ] 3 => array:2 [ "nombre" => "O.R." "apellidos" => "Díaz-Sánchez" ] 4 => array:2 [ "nombre" => "M.T." "apellidos" => "Hernández-García" ] 5 => array:2 [ "nombre" => "J.M." "apellidos" => "Raya" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Hematología y Hemoterapia, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Importancia del diagnóstico precoz en policitemia vera y trombocitemia esencial. Experiencia de un centro" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1367 "Ancho" => 2925 "Tamanyo" => 218019 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Kaplan-Meier curves for overall survival in patients with PV (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>a) and in patients with ET (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>b) according to the presence of thrombosis prior to diagnosis (blue) or the absence of thrombosis prior to diagnosis (red).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Polycythaemia vera (PV) and essential thrombocythemia (ET) are types of chronic myeloproliferative neoplasms. They are slow-evolving diseases with long-term survival, this being superior for ET than for PV<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>. Thrombotic events are the main complication in patients with either of these entities.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Thrombosis frequently precedes disease diagnosis or is the reason that leads to diagnosis. Approximately 25% of patients with ET or PV have experienced a thrombotic event prior to diagnosis<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>. Some patients who have had a thrombotic episode prior to diagnosis had documented erythrocytosis or thrombocytosis in prior analyses but had not been referred to a haematologist. One would expect that, if diagnosis had been made and treatment initiated prior to the thrombosis, then a large part of these thromboses could have been prevented.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The aim of this study was to investigate what proportion of patients who experienced a thrombotic episode prior to diagnosis had previously documented thrombocytosis or erythrocytosis given that in those cases the thrombosis potentially could have been prevented. In addition, we pose the question of whether the previous thrombotic episodes influence patient survival.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">We conducted a retrospective analysis of patients with PV and ET from our centre who were diagnosed between 1986 and 2020 for PV and between 2003 and 2020 for ET. The patients met the current diagnostic criteria for PV and ET at the time of diagnosis<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3–7</span></a>. Erythrocytosis was defined as repeated Hb > 16 g/dL in females and Hb > 16.5 g/dL in males, and thrombocytosis as a sustained platelet count >450,000/mm<span class="elsevierStyleSup">3</span>.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Statistical analysis was performed using the SPSS® program (Statistical Package for the Social Sciences, Chicago, USA) version 15.0. We used the Kaplan-Meier method for the survival time probabilities and the survival curves and the log-rank test for the differences between curves.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0030" class="elsevierStylePara elsevierViewall">We studied 63 patients with PV (37 male and 26 female) and 130 patients with ET (76 female and 54 male). The mean age at diagnosis was 61 years for PV (range: 28–93 years) and 64 years for ET (range: 24–89 years). A total of 58.7% and 61.5% of the patients with PV and ET, respectively, were aged 60 years or older at diagnosis.</p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Polycythaemia vera</span><p id="par0035" class="elsevierStylePara elsevierViewall">Of the 63 patients with PV, a mutation study of JAK2 was performed on 56 patients and mutation was found in all of them; 49 (87.5%) had heterozygous V617F mutation (exon 14); 5 patients (8.9%) homozygous V617F mutation, and 2 patients (3.5%) mutation of exon 12.</p><p id="par0040" class="elsevierStylePara elsevierViewall">In our series, 17 patients (27%) experienced thrombosis prior to diagnosis. In 7 of them (11.1%), the thrombotic event occurred without prior knowledge of erythrocytosis nor its presence at the time of the event; in 3 cases (4.8%), detection of an initial analysis with erythrocytosis coincided with the same thrombotic event; the remaining 7 cases (11.1%) had documented polyglobulia in various prior analyses. In this last group, the median time between the first analysis with erythrocytosis and the thrombotic event was 8.2 months (range: 4–123 months).</p><p id="par0045" class="elsevierStylePara elsevierViewall">The median time between the thrombotic event and PV diagnosis in those patients who had documented polyglobulia before or during the thrombotic event was 6.5 months (range: 13 days to 137 months).</p><p id="par0050" class="elsevierStylePara elsevierViewall">For the overall group of 63 patients, regardless of whether they did or did not present with prior thrombosis, the median time between when erythrocytosis was observed for the first time until the patient was seen in the haematology clinic was 11.2 months (range: 13 days to 137 months).</p><p id="par0055" class="elsevierStylePara elsevierViewall">These patients, those who experienced thrombosis prior to diagnosis, had significantly lower overall survival than the rest (<span class="elsevierStyleItalic">p</span> = 0.006; <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>a). Mean age at diagnosis for patients with prior thrombosis was 69.5 years and 59.2 years for those without prior thrombosis, however this difference was not significant (<span class="elsevierStyleItalic">p</span> = 0.31).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">On the other hand, throughout the evolution of the disease, only 4 patients (6.3%) experienced thrombosis. It is worth noting that 2 of these patients were not receiving antiplatelet therapy when the thrombotic event occurred.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Essential thrombocythemia</span><p id="par0065" class="elsevierStylePara elsevierViewall">Of the 130 patients studied, 76 had V617F mutation of the JAK2 gene (58.5%); 23 patients had mutation of the CALR gene (17.7%); one patient had mutation of the MPL gene and 18 were triple negatives (13.8%). In addition, JAK2 V617F mutation was ruled out in 10 patients, but no study of other genes was carried out and 2 other patients had no mutation study.</p><p id="par0070" class="elsevierStylePara elsevierViewall">On the other hand, a total of 25 patients (19.2%) experienced a thrombotic event prior to diagnosis: in 10 cases (7.7% of the total) there was no thrombocytosis when the event occurred; in 5 cases (3.8%) the thrombocytosis was observed at the same time as the thrombosis or just beforehand (<3 months), and 10 cases (7.7%) had documented thrombocytosis at least 3 months prior.</p><p id="par0075" class="elsevierStylePara elsevierViewall">In this last group, the median time between observing thrombocytosis and the thrombotic event was 11.8 months (range: 7–181 months). The median time between thrombosis and ET diagnosis in patients with prior thrombocytosis or in the thrombotic event was 16.7 months (range: 11 days to 133 months).</p><p id="par0080" class="elsevierStylePara elsevierViewall">Overall, regardless of whether the patients had experienced a prior thrombotic event or not, the median time between the first evidence of thrombocytosis and the ET diagnosis was 17.2 months (range: 11 days to 197 months).</p><p id="par0085" class="elsevierStylePara elsevierViewall">These patients with a thrombotic episode prior to diagnosis had a significantly lower overall survival than those who had not experienced a thrombotic episode (<span class="elsevierStyleItalic">p</span> < 0.001; <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>b). Mean age at diagnosis was 75 years in the patients with prior thrombosis and 61 years for the group with no prior thrombosis, though this difference was not significant (<span class="elsevierStyleItalic">p</span> = 0.26).</p><p id="par0090" class="elsevierStylePara elsevierViewall">During disease evolution, 12 patients (9.2%) presented a thrombotic event: 6 with JAK2 mutation; 5 with CALR mutation, and one with no mutation study. Remarkably, as we saw in the PV group, 7 of these 12 patients were not receiving antiplatelet therapy at the time of the event.</p><p id="par0095" class="elsevierStylePara elsevierViewall">The main clinical and demographic characteristics of the patients with prior thrombosis at the time of diagnosis are detailed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> for both PV and ET.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discussion and conclusion</span><p id="par0100" class="elsevierStylePara elsevierViewall">This study shows that, in our setting, approximately 40% of patients who experience thrombosis prior to PV or ET diagnosis already had previously documented polyglobulia or thrombocytosis. Nevertheless, this was not the reason for referring the patient to a specialist. Even when some patients experience a thrombotic event, though some are quickly referred, others may not see a haematologist for years.</p><p id="par0105" class="elsevierStylePara elsevierViewall">In our series, we did not find a single patient who, having documented erythrocytosis or thrombocytosis, had suffered a second thrombotic event prior to disease diagnosis; this is likely because antiplatelet drugs (or occasionally anticoagulants) would have been prescribed following the first thrombotic episode.</p><p id="par0110" class="elsevierStylePara elsevierViewall">We believe that a majority of these thromboses occurring in patients with previously documented erythrocytosis or thrombocytosis could have been prevented via early diagnosis and treatment. In our opinion, early diagnosis depends on primary care physicians and other specialists being properly trained in the screening criteria for these diseases so that these patients can be seen by a haematologist prior to developing thrombosis.</p><p id="par0115" class="elsevierStylePara elsevierViewall">As with other studies<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,9</span></a>, we discovered that patients with prior thrombosis have a lower survival rate. Though more in-depth research is required, we interpret this difference in survival rate to be at least partially due to the sequelae of the very first thrombotic episode. Therefore, if early diagnosis can reduce thrombotic episodes, it could also have an impact on patient survival and quality of life by preventing the morbidity associated with those episodes.</p><p id="par0120" class="elsevierStylePara elsevierViewall">Early diagnosis and treatment of these diseases does not prevent these patients from developing thrombosis in the evolution of their disease. In our series, 6.3% (for PV) and 9.2% (for ET) developed a thrombotic event in the evolution of the disease. Remarkably, all together, more than half of the patients were not receiving treatment with antiplatelet drugs at the time of the thrombotic episode, which reinforces the importance of antiplatelet therapy in these patients, a datum that has been expressed in multiple studies<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>.</p><p id="par0125" class="elsevierStylePara elsevierViewall">It has recently been communicated that the clonal origin of chronic myeloproliferative neoplasms occurs many years prior to the presentation of the proliferative phenotype<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11,12</span></a>. In addition, it has been observed that a small percentage of patients with thrombosis have the JAK2 V617F mutation without hemogram alteration<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13,14</span></a>. In this sense, it is possible that thrombotic events that occurred in patients with PV or ET prior to diagnosis and with a normal hemogram may be conditioned by an initial phase of the disease without obvious myeloproliferation, but with greater thrombotic risk.</p><p id="par0130" class="elsevierStylePara elsevierViewall">In conclusion, early diagnosis of PV and ET following detection of erythrocytosis or thrombocytosis could prevent up to 40% of thromboses pre-diagnosis and accordingly increase survival and likely improve quality of life for these patients. Appropriate training for primary care physicians and physicians from different specialities seems to be key to achieving this goal.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Funding</span><p id="par0135" class="elsevierStylePara elsevierViewall">The authors declare they have not received any funding to carry out this study.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflicts of interest</span><p id="par0140" class="elsevierStylePara elsevierViewall">The authors declare that they do not have any conflicts of interest that could influence the results of this study or their interpretation.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1672386" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1484332" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1672387" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1484333" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Material and methods" ] 6 => array:3 [ "identificador" => "sec0015" "titulo" => "Results" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Polycythaemia vera" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Essential thrombocythemia" ] ] ] 7 => array:2 [ "identificador" => "sec0030" "titulo" => "Discussion and conclusion" ] 8 => array:2 [ "identificador" => "sec0035" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflicts of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-03-13" "fechaAceptado" => "2021-07-01" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1484332" "palabras" => array:3 [ 0 => "Polycythemia vera" 1 => "Essential thrombocythemia" 2 => "Chronic myeloproliferative neoplasms" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1484333" "palabras" => array:3 [ 0 => "Policitemia vera" 1 => "Trombocitemia esencial" 2 => "Neoplasias mieloproliferativas crónicas" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objectives</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">This work aims to describe the proportion of patients with polycythemia vera (PV) or essential thrombocythemia (ET) and thrombosis prior to the diagnosis who had erythrocytosis or thrombocytosis prior to the thrombosis.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">This is a retrospective review of 63 patients with PV and 130 with ET.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">In regard to PV, we found prior erythrocytosis in 7 (11.1%) of the 17 cases (27%) with thrombosis prior to diagnosis. In ET, we found prior thrombocytosis in 10 (7.7%) of the 25 cases (19.2%) with thrombosis prior to diagnosis. The median time between the laboratory finding and thrombosis was 8.2 months and 11.8 months for PV and TE, respectively. In both entities, patients with thrombosis prior to diagnosis had significantly lower survival.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">A significant proportion of patients with thrombosis prior to the diagnosis of PV and ET present with erythrocytosis or thrombocytosis prior to the episode of thrombosis. This could allow for anticipating diagnosis and treatment.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivos</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Describir la proporción de pacientes con policitemia vera (PV) o trombocitemia esencial (TE) y trombosis previa al diagnóstico que presentaban eritrocitosis o trombocitosis antes de la trombosis.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y métodos</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Revisión retrospectiva de 63 pacientes con PV y 130 con TE.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">En PV, encontramos eritrocitosis previa en 7 (11,1%) de los 17 casos (27%) con trombosis previa al diagnóstico. En TE, encontramos trombocitosis previa en 10 (7,7%) de los 25 casos (19,2%) con trombosis previa al diagnóstico. La mediana de tiempo entre el hallazgo analítico y la trombosis fue 8,2 meses y 11,8 meses para PV y TE respectivamente. En ambas entidades, los pacientes con trombosis previa al diagnóstico tenían una supervivencia significativamente menor.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusión</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Una proporción significativa de pacientes con trombosis previa al diagnóstico de PV y TE presenta eritrocitosis o trombocitosis previa al episodio de trombosis, lo que permitiría anticipar el diagnóstico y el tratamiento.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Lakhwani S, Pardina-Echevarría M, Arcas-Vega R, Díaz-Sánchez OR, Hernández-García MT, Raya JM. Importancia del diagnóstico precoz en policitemia vera y trombocitemia esencial. Experiencia de un centro. Rev Clin Esp. 2022;222:169–173.</p>" ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1367 "Ancho" => 2925 "Tamanyo" => 218019 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Kaplan-Meier curves for overall survival in patients with PV (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>a) and in patients with ET (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>b) according to the presence of thrombosis prior to diagnosis (blue) or the absence of thrombosis prior to diagnosis (red).</p>" ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Characteristics at diagnosis of the patients with PV and ET who had previous thrombosis. The quantitative variables are expressed as medians and ranges and the qualitative variables are expressed in numbers and percentages.</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">AMI: acute myocardial infarction; DVT: deep vein thrombosis; LL: lower limbs; PE: pulmonary embolism.</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"> \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">Polycythemia vera, n = 17 \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">Essential thrombocythemia, n = 25 \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">Age (years) \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">71 (41−93) \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">77 (55−89) \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">Male sex \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">9 (53%) \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 (48%) \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">Haematocrit (%) \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">56 (47.9−67.7) \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">41.2 (33.1−53.6) \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">Haemoglobin (g/dL) \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">18.1 (16.3−22.3) \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">13.5 (10.8−17.3) \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">Platelets ×10<span class="elsevierStyleSup">3</span>/mm<span class="elsevierStyleSup">3</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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">479 (245−1124) \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">784 (465−1771) \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">Leukocytes ×10<span class="elsevierStyleSup">3</span>/mm<span class="elsevierStyleSup">3</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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.8 (7−21.2) \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">9.9 (6−17.2) \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">Splenomegaly (%) \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">5 (29) \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">7 (28) \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">Urid acid (mg/dL) \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">7.2 (3.2−9.2) \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">5.7 (3.8−9.5) \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">Total cholesterol (mg/dL) \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">129 (112−230) \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">153 (107−279) \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">Thrombosis type and location \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"><span class="elsevierStyleItalic">Arterial:</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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Arterial:</span> \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"> \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">- Cerebral 10 (59%) \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">- Cerebral 10 (40%) \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"> \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">- AMI 5 (29%) \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">- AMI 7 (28%) \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"> \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"> \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">- LL 3 (12%) \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"> \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"><span class="elsevierStyleItalic">Venous:</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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Venous:</span> \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"> \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">- DVT/PE 2 (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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- DVT/PE 5 (20%) \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">Observed mutations \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">- JAK2 V617F heterozygous 14 (82%) \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">- JAK2 V617F 15 (60%) \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"> \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">- JAK2 V617F homozygous 1 (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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- CALR 2 (8%) \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"> \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">- JAK2 Exon 12 1 (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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- MPL 1 (4%) \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"> \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">- Not studied 1 (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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- Triple negative 3 (12%) \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"> \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"> \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">- JAK2 not mutated 4 (16%) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2845759.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Characteristics of the patients with previous thrombosis.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:14 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. 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