Letter to the Editor
Thrombopoietin-receptor agonist as a treatment of thrombocytopenia associated with systemic lupus erythematosus
Agonista del receptor de trombopoyetina como tratamiento de trombocitopenia asociada a lupus eritematoso sistémico
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Moreno Ramos" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Maria José" "apellidos" => "Moreno Martínez" "email" => array:1 [ 0 => "mjmorenomartinez@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Pilar" "apellidos" => "Gallego" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Manuel J." "apellidos" => "Moreno Ramos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Reumatología, Hospital Universitario Rafael Méndez, Lorca, Murcia, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Hematología, Hospital Universitario Rafael Méndez, Lorca, Murcia, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Reumatología, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Agonista del receptor de trombopoyetina como tratamiento de trombocitopenia asociada a lupus eritematoso sistémico" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Systemic lupus erythematosus (SLE) is a disease that is characterized by both the clinical manifestations and the analytical findings. According to published series, up to 30% of the patients with SLE have thrombocytopenia.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">A number of approaches have been used to treat thrombocytopenia and other hematological disorders in SLE patients (glucocorticoids, intravenous immunoglobulins, cyclophosphamide, rituximab and splenectomy, among others).<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">We present the case of a woman with SLE and associated autoimmune thrombocytopenia, refractory to conventional therapies, that responded satisfactorily to treatment with a thrombopoietin-receptor agonist.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The patient was a 39-year-old woman who, in 2010, had been diagnosed with SLE on the basis of thrombocytopenia, arthritis and positive tests for antinuclear, anti-Sm, anti-Ro and anti-La antibodies. Treatment was started with hydroxychloroquine (200<span class="elsevierStyleHsp" style=""></span>mg/day) and low-dose glucocorticoids (5<span class="elsevierStyleHsp" style=""></span>mg of prednisone daily), which produced an improvement in all the manifestations except thrombocytopenia. The patient's platelet count reached levels as low as 5000/μL, and she experienced occasional epistaxis, as well as metrorrhagia. Thus, treatment was attempted with prednisone at a dose of 0.5<span class="elsevierStyleHsp" style=""></span>mg/kg/day, which was changed, in succession, to mycophenolate (2<span class="elsevierStyleHsp" style=""></span>mg/kg/day), azathioprine (100<span class="elsevierStyleHsp" style=""></span>mg/day) and rituximab, with no improvement. This led us to consult with hematologists from our hospital, and a joint decision was made to initiate treatment with oral eltrombopag (a thrombopoietin-receptor agonist) at 50<span class="elsevierStyleHsp" style=""></span>mg once daily. After 1 month of treatment, we observed an increase in the platelet count, which reached a high of 168<span class="elsevierStyleHsp" style=""></span>000/μL, making it possible to reduce the prednisone dose to 2.5<span class="elsevierStyleHsp" style=""></span>mg/day.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In the literature, we found six cases of refractory thrombocytopenia associated with SLE in which there was a good response to treatment with a thrombopoietin-receptor agonist. All the patients responded to this treatment within a period of 1–3<span class="elsevierStyleHsp" style=""></span>weeks, after their disease had proved refractory to a multitude of immunomodulatory therapies (corticosteroids, intravenous immunoglobulins, rituximab, cyclophosphamide, azathioprine and splenectomy).<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">3</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The mechanisms proposed as the major causes of thrombocytopenia in SLE are antibody-mediated platelet destruction, alterations in thrombopoiesis and thrombotic microangiopathy/presence of antiphospholipid antibodies.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">1,4</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">After binding to its receptor, thrombopoietin induces the maturation of megakaryocytes. Systemic lupus erythematosus patients are positive to anti-thrombopoietin antibodies, and the levels of thrombopoietin are low.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">3</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The thrombopoietin-receptor agonists, eltrombopag and romiplostim, stimulate the proliferation and maturation of megakaryocytes in the bone marrow. These drugs are used regularly in hematology to treat chronic autoimmune thrombocytopenia.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">1–4</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Romiplostim is administered subcutaneously once a week at doses that range from 1 to 10<span class="elsevierStyleHsp" style=""></span>μg/kg. Eltrombopag is administered orally at doses of 25, 50 or 75<span class="elsevierStyleHsp" style=""></span>mg a day.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">1,3</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Despite the favorable and encouraging results, romiplostim and eltrombopag do have secondary effects, and an increase in the incidence of thrombosis (of around 6.5%) has been reported after sustained treatment with these drugs.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">3</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0055" class="elsevierStylePara elsevierViewall">This work has received no funding.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Moreno Martínez MJ, Gallego P, Moreno Ramos MJ. Agonista del receptor de trombopoyetina como tratamiento de trombocitopenia asociada a lupus eritematoso sistémico. Reumatol Clin. 2016;12:57.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:4 [ 0 => array:3 [ "identificador" => "bib0025" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Thrombopoietin levels in systemic lupus erythematosus are linked to inflammatory cytokines, but unrelated to thrombocytopenia or thrombosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C. Lu" 1 => "J. Nossent" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/0961203314547796" "Revista" => array:6 [ "tituloSerie" => "Lupus" "fecha" => "2015" "volumen" => "24" "paginaInicial" => "18" "paginaFinal" => "24" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25117655" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0030" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Immune thrombocytopenia and B-cell-activating factor/a proliferation-inducing ligand" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "X.G. Liu" 1 => "M. Hou" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.seminhematol.2013.03.021" "Revista" => array:6 [ "tituloSerie" => "Semin Hematol" "fecha" => "2013" "volumen" => "50" "paginaInicial" => "S89" "paginaFinal" => "S99" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23664525" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0035" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effectiveness of thrombopoietin-receptor agonists in the treatment of refractory immune thrombocytopenia associated to systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "L. Magnano" 1 => "H. Enríquez" 2 => "J. Esteve" 3 => "R. Cervera" 4 => "G. Espinosa" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3899/jrheum.140080" "Revista" => array:6 [ "tituloSerie" => "J Rheumatol" "fecha" => "2014" "volumen" => "41" "paginaInicial" => "1895" "paginaFinal" => "1896" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25179983" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0040" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autoimmunity and novel therapies in immune-mediated thrombocytopenia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "D. Yehudai" 1 => "E. Toubi" 2 => "Y. Shoenfeld" 3 => "Z. Vadasz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.seminhematol.2013.03.015" "Revista" => array:6 [ "tituloSerie" => "Semin Hematol" "fecha" => "2013" "volumen" => "50" "paginaInicial" => "S100" "paginaFinal" => "S108" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23664506" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735743/0000001200000001/v1_201601240019/S2173574315001239/v1_201601240019/en/main.assets" "Apartado" => array:4 [ "identificador" => "8400" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735743/0000001200000001/v1_201601240019/S2173574315001239/v1_201601240019/en/main.pdf?idApp=UINPBA00004M&text.app=https://reumatologiaclinica.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574315001239?idApp=UINPBA00004M" ]
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| 2016 December | 55 | 13 | 68 |
| 2016 November | 54 | 10 | 64 |
| 2016 October | 52 | 16 | 68 |
| 2016 September | 64 | 9 | 73 |
| 2016 August | 48 | 9 | 57 |
| 2016 July | 23 | 11 | 34 |
| 2016 April | 1 | 0 | 1 |
| 2016 February | 3 | 40 | 43 |
| 2016 January | 3 | 17 | 20 |
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