Case Report
Relapsed Hydroxychloroquine Induced Thrombocytopenia in Systemic Lupus Erythematosus Patient
Trombocitopenia recurrente inducida por hidroxicloroquina en ausencia de actividad del lupus eritematoso sistémico
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ATC, anatomical therapeutic chemical; INN, international nonproprietary name. *The examples are provided for illustrative purposes. It should be remembered that Remsima and Inflectra are the same product. Modification from Vermeer et al.<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">48</span></a></p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "José M. Serra López-Matencio, Alberto Morell Baladrón, Santos Castañeda" "autores" => array:3 [ 0 => array:2 [ "nombre" => "José M." 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The diagnosis revealed antinuclear antibodies (ANA) at a titer of 1:320, negative results for anti-double strand (ds) DNA antibodies, normal levels of complement component C3 and C4, and a systemic lupus erythematosus disease activity index (SLEDAI) of 11. Despite treatment with immunosuppressive agents and maintenance with mycophenolate sodium (360<span class="elsevierStyleHsp" style=""></span>mg/12<span class="elsevierStyleHsp" style=""></span>h) and hydroxychloroquine (200<span class="elsevierStyleHsp" style=""></span>mg/day), the patient developed class II lupus nephritis with an activity index of 1/12 and of chronicity of 0/12. Renal biopsy was performed in June 2011: light microscopic study of 10 glomeruli showed moderate focal and segmental mesangial hypercellularity, although there were no lesions indicative of necrotic activity, karyorrhexis, crescents or fuchsinophilic deposits. Cellularity was preserved and there was no tubulointerstitial fibrosis or atrophy. Immunofluorescence of 4 glomeruli was positive, with a pure mesangial glomerular pattern. Some paramesangial deposits were focally and segmentally isolated. There was no evidence of parietal deposits. Tests revealed IgG−/+, IgA++, C3++, C1q−/+, Kappa+/+ and Lambda+/+. Negative findings in vessels, interstitium and tubules.</p><p id="par0015" class="elsevierStylePara elsevierViewall">He had a proteinuria of 5<span class="elsevierStyleHsp" style=""></span>g/day detected in May 2015 and was admitted to the hospital for another renal biopsy. During his hospital stay, he was found to have asymptomatic thrombocytopenia, 4<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span><span class="elsevierStyleHsp" style=""></span>cells/L, with no signs of cellular atypia, negative results on tests for antiplatelet and antihistone antibodies and a SLEDAI of 9. He began to take corticosteroids at a dose of 1<span class="elsevierStyleHsp" style=""></span>mg/kg body weight (bw)/day, with a diagnosis of autoimmune thrombocytopenia. Immunosuppressive therapy was maintained, and hydroxychloroquine, which was not prescribed, was discontinued. After 48<span class="elsevierStyleHsp" style=""></span>h, he had a rapid platelet recovery, reaching 195<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span><span class="elsevierStyleHsp" style=""></span>cells/L. This enabled the performance of the renal biopsy, which revealed a progression of the lupus nephritis, from class II to class V (membranous glomerulonephritis). Renal biopsy was repeated in July 2015. Light microscopic study ruled out the presence of lesions indicative of proliferative glomerulonephritis; there was no tubulointerstitial fibrosis and immunofluorescence of 5 glomeruli showed a generalized, diffuse glomerular parietal pattern: IgG+++, IgA++, IgM+/−, C3+++, C1q+, Kappa+++ and Lambda+++. Findings in vessels, interstitium and tubules were negative.</p><p id="par0020" class="elsevierStylePara elsevierViewall">At discharge, a different physician again prescribed combined therapy with mycophenolate and hydroxychloroquine (200<span class="elsevierStyleHsp" style=""></span>mg/day). The patient was readmitted 72<span class="elsevierStyleHsp" style=""></span>h after discharge due to a new episode of severe thrombocytopenia, with no signs of lupus activity (negative test for anti-dsDNA antibodies and normal C3 and C4 levels). He began to take corticosteroids again (1<span class="elsevierStyleHsp" style=""></span>mg/kg bw/day), without platelet recovery.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Given the rapid cause-and-effect relationship between hydroxychloroquine and thrombocytopenia, the drug was discontinued intentionally. Within 72<span class="elsevierStyleHsp" style=""></span>h, the platelet count reached 200<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span><span class="elsevierStyleHsp" style=""></span>cells/L (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">During follow-up, after 1 month, the total platelet count was 250<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span><span class="elsevierStyleHsp" style=""></span>cells/L and, in analyses performed 3 and 6 months later, there had been no decrease (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). He began to take tacrolimus because of the progression of nephritis.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0035" class="elsevierStylePara elsevierViewall">Drug-induced thrombocytopenia is based on the accelerated destruction of platelets that can occur via 2 different mechanisms: due to direct toxicity acting on the bone marrow or due to peripheral destruction by means of a mechanism that may or may not be immune-mediated by specific antibodies that react with the drug.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2,3</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The drugs that have been most frequently related to the development of thrombocytopenia are cinchona alkaloids (quinine/quinidine), sulfonamides, nonsteroidal anti-inflammatory drugs, diuretics, anticonvulsants, tuberculostatic drugs and heparins.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,4</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The diagnosis of drug-induced thrombocytopenia is established by exclusion, by interrupting administration of the drug and by the detection of drug-dependent antibodies. The temporal relationship between the administration of the treatment and the development of thrombocytopenia is highly important, as is recurrence after re-exposure to the drug.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4,5</span></a> In our patient, the discontinuance of the medication was used as a method of exclusion.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Reaching the definitive diagnosis in the case we report was complex, given that the first manifestation of SLE in our patient was thrombocytopenia. There is a form of clinical presentation in SLE consisting of chronic thrombocytopenia with a slight response to corticosteroids.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> Thus, the initial diagnostic suspicion focused on the exacerbation of the lupus activity, in a patient in whom, moreover, the disease had progressed to renal involvement.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Hydroxychloroquine is an antimalarial drug employed in the treatment of lupus and other rheumatic diseases. A number of retrospective studies have shown the efficacy of hydroxychloroquine in the treatment of the autoimmune thrombocytopenia associated with SLE. The authors recommend that the medication not to be discontinued, even in advanced stages of lupus nephritis. Nevertheless, the secondary effects of that drug include thrombocytopenia,<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> although it is not a common adverse effect, given that there are only isolated cases reported in the literature.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8–10</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclusion</span><p id="par0060" class="elsevierStylePara elsevierViewall">Finally, we consider this case to be of clinical and practical interest, because the cause of the thrombocytopenia was related to hydroxychloroquine and not to the lupus activity, which at all times was clinically and serologically inactive, despite the severity of the thrombocytopenia.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Ethical Disclosures</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Protection of human and animal subjects</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Confidentiality of data</span><p id="par0070" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Right to privacy and informed consent</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors have obtained the written informed consent of the patients or subjects mentioned in the article. The corresponding author is in possession of this document.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conflicts of Interest</span><p id="par0080" class="elsevierStylePara elsevierViewall">The authors declare they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres884938" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec871138" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres884939" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec871137" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Case Report" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Conclusion" ] 8 => array:3 [ "identificador" => "sec0025" "titulo" => "Ethical Disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0040" "titulo" => "Right to privacy and informed consent" ] ] ] 9 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflicts of Interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-03-04" "fechaAceptado" => "2016-04-18" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec871138" "palabras" => array:3 [ 0 => "Hydroxychloroquine" 1 => "Thrombocytopenia" 2 => "Systemic lupus erythematosus" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec871137" "palabras" => array:3 [ 0 => "Hidroxicloroquina" 1 => "Trombocitopenia" 2 => "Lupus eritematoso sistémico" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Hydroxychloroquine is used in the long-term therapy of systemic lupus erythematosus (SLE). Although considered to be a safe treatment, side effects have been documented. An uncommon side effect is thrombocytopenia. In order to establish the diagnosis of thrombocytopenia secondary to Hydroxychloroquine, non-pharmacological causes must be ruled out and it is necessary to determine a recurrence after re-exposure to the drug. We present one case of severe thrombocytopenia occurring in a patient with SLE undergoing treatment with Hydroxychloroquine.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La hidroxicloroquina es un fármaco antimalárico, empleado como terapia a largo plazo en el lupus eritematoso sistémico (LES). A pesar de considerarse un tratamiento seguro, existen efectos adversos descritos. Uno muy infrecuente es la trombocitopenia. Para establecer el diagnóstico de trombocitopenia causada por hidroxicloroquina es necesario descartar otras causas no farmacológicas y objetivar la recurrencia tras la reexposición al fármaco. Presentamos un caso de trombocitopenia severa en un paciente con LES durante el tratamiento con hidroxicloroquina.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Vázquez VA, Pascual L, Corominas Macias H, Giménez Torrecilla I. Trombocitopenia recurrente inducida por hidroxicloroquina en ausencia de actividad del lupus eritematoso sistémico. Reumatol Clin. 2017;13:294–296.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 578 "Ancho" => 1524 "Tamanyo" => 71373 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Changes in platelet counts in relation to exposure to hydroxychloroquine (HCQ).</p>" ] ] 1 => 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:1 [ "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="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Platelets \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Hemoglobin \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Leukocytes \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Lymphocytes \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Anti-DNA \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">C3 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">C4 \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">175<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">141<span class="elsevierStyleHsp" style=""></span>g/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.2<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.6<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.15 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HCQ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">140<span class="elsevierStyleHsp" style=""></span>g/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.4<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.13 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">STOP HCQ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">195<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">154<span class="elsevierStyleHsp" style=""></span>g/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.8<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.7<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.22 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HCQ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">153<span class="elsevierStyleHsp" style=""></span>g/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.8<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.19 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">STOP HCQ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">250<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">148<span class="elsevierStyleHsp" style=""></span>g/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.5<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.5<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1494223.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Platelet Count, White Blood Cells, Red Blood Cells, Anti-DNA and Complement According to Exposure to and Interruption of Hydroxychloroquine (HCQ).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "International consensus report on the investigation and management of primary immune thrombocytopenia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 33 | 17 | 50 |
| 2024 October | 247 | 36 | 283 |
| 2024 September | 276 | 19 | 295 |
| 2024 August | 273 | 30 | 303 |
| 2024 July | 229 | 27 | 256 |
| 2024 June | 214 | 50 | 264 |
| 2024 May | 170 | 36 | 206 |
| 2024 April | 173 | 34 | 207 |
| 2024 March | 155 | 26 | 181 |
| 2024 February | 160 | 30 | 190 |
| 2024 January | 176 | 26 | 202 |
| 2023 December | 129 | 23 | 152 |
| 2023 November | 133 | 20 | 153 |
| 2023 October | 131 | 37 | 168 |
| 2023 September | 168 | 42 | 210 |
| 2023 August | 182 | 16 | 198 |
| 2023 July | 123 | 18 | 141 |
| 2023 June | 150 | 19 | 169 |
| 2023 May | 124 | 22 | 146 |
| 2023 April | 106 | 11 | 117 |
| 2023 March | 154 | 30 | 184 |
| 2023 February | 138 | 37 | 175 |
| 2023 January | 126 | 8 | 134 |
| 2022 December | 149 | 43 | 192 |
| 2022 November | 109 | 32 | 141 |
| 2022 October | 144 | 37 | 181 |
| 2022 September | 124 | 51 | 175 |
| 2022 August | 81 | 30 | 111 |
| 2022 July | 109 | 38 | 147 |
| 2022 June | 86 | 32 | 118 |
| 2022 May | 98 | 41 | 139 |
| 2022 April | 126 | 58 | 184 |
| 2022 March | 94 | 49 | 143 |
| 2022 February | 126 | 31 | 157 |
| 2022 January | 132 | 47 | 179 |
| 2021 December | 96 | 40 | 136 |
| 2021 November | 136 | 40 | 176 |
| 2021 October | 133 | 72 | 205 |
| 2021 September | 126 | 40 | 166 |
| 2021 August | 110 | 42 | 152 |
| 2021 July | 94 | 37 | 131 |
| 2021 June | 141 | 24 | 165 |
| 2021 May | 112 | 41 | 153 |
| 2021 April | 264 | 111 | 375 |
| 2021 March | 233 | 45 | 278 |
| 2021 February | 94 | 20 | 114 |
| 2021 January | 126 | 19 | 145 |
| 2020 December | 139 | 27 | 166 |
| 2020 November | 282 | 25 | 307 |
| 2020 October | 145 | 18 | 163 |
| 2020 September | 174 | 35 | 209 |
| 2020 August | 209 | 21 | 230 |
| 2020 July | 166 | 11 | 177 |
| 2020 June | 118 | 18 | 136 |
| 2020 May | 144 | 19 | 163 |
| 2020 April | 236 | 34 | 270 |
| 2020 March | 76 | 10 | 86 |
| 2020 February | 2 | 0 | 2 |
| 2019 January | 2 | 0 | 2 |
| 2018 October | 0 | 1 | 1 |
| 2018 May | 8 | 0 | 8 |
| 2018 April | 116 | 10 | 126 |
| 2018 March | 113 | 12 | 125 |
| 2018 February | 87 | 11 | 98 |
| 2018 January | 76 | 11 | 87 |
| 2017 December | 76 | 26 | 102 |
| 2017 November | 80 | 21 | 101 |
| 2017 October | 89 | 36 | 125 |
| 2017 September | 61 | 38 | 99 |
| 2017 August | 35 | 23 | 58 |
| 2017 July | 7 | 17 | 24 |
| 2017 June | 4 | 15 | 19 |
| 2017 May | 4 | 9 | 13 |
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