Scientific letter
Cyclosporin-induced thrombotic thrombocytopenic purpura. Report of three cases
Púrpura trombótica trombocitopénica inducida por ciclosporina. Estudio de 3 casos
Pablo Selvi Sabater
, Alberto Espuny Miró, Angela Maria Rizo Cerdá, José Enrique de la Rubia Orti
Corresponding author
Servicio de Farmacia, Hospital General Universitario Morales Meseguer, Murcia, Spain
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Report of three cases" "tieneTextoCompleto" => true "saludo" => "Dear Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "231" "paginaFinal" => "232" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Pablo Selvi Sabater, Alberto Espuny Miró, Angela Maria Rizo Cerdá, José Enrique de la Rubia Orti" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Pablo" "apellidos" => "Selvi Sabater" "email" => array:1 [ 0 => "pbselvi@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Alberto" "apellidos" => "Espuny Miró" ] 2 => array:2 [ "nombre" => "Angela Maria" "apellidos" => "Rizo Cerdá" ] 3 => array:2 [ "nombre" => "José Enrique" "apellidos" => "de la Rubia Orti" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Farmacia, Hospital General Universitario Morales Meseguer, Murcia, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Púrpura trombótica trombocitopénica inducida por ciclosporina. Estudio de 3 casos" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Thrombotic thrombocytopenic purpura (TTP) was first described by Moschcowitz in 1925.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a> TTP should be suspected when a patient presents with: microangiopathic haemolytic anaemia with peripheral blood schistocytes,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">2</span></a> haptoglobin reduction and increased LDH,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">3</span></a> thrombocytopenia,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">4</span></a> acute renal failure, neurological disorders and, in some cases, fever.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Cyclosporine can cause renal thrombotic microangiopathy with clinical manifestations of TTP (reaction described in the summary of product characteristics as rare: ≥1/10,000, <1/1000).<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">6</span></a> This form of TTP is often, but not always, reversible with treatment discontinuation.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">6,7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">3 patients undergoing hematopoietic stem cell transplant who received cyclosporine as immunosuppressive therapy are reported.</p><p id="par0020" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patient 1</span>. Male, 61 years of age at the time of transplantation, diagnosed with stage IVB diffuse large B-cell non-Hodgkin lymphoma, who underwent allogeneic peripheral blood stem cell transplant from an unrelated donor, HLA-compatible and ABO. The patient started on day +8 with increased bilirubin, and after ruling out the hepatic veno-occlusive disease, intravascular haemolysis data were observed with increased LDH levels reaching 972<span class="elsevierStyleHsp" style=""></span>IU/l, decreased platelet count (9<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L), haemoglobin decrease (90<span class="elsevierStyleHsp" style=""></span>g/l), haptoglobine decrease (0.05<span class="elsevierStyleHsp" style=""></span>g/l) and presence of schistocytes in peripheral blood.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In addition, there is evidence of renal involvement with increased creatinine levels in blood.</p><p id="par0030" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patient 2</span>. Female, 14 years of age at the time of transplantation, diagnosed of acute lymphoblastic leukaemia with 11q abnormalities and skin infiltration. Compatible with the diagnosis of acute lymphoblastic leukaemia ALL-L2 (FAB), Pre-B acute leukaemia (EGIL B-III), Precursor B-cell ALL (WHO). She underwent allogeneic peripheral blood stem cell transplant from an unrelated donor, HLA-compatible and ABO-compatible. The patient began on day +30 with data which demonstrated haemolysis with increased LDH levels reaching 1368<span class="elsevierStyleHsp" style=""></span>IU/l, decreased platelet count (30<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L), haemoglobin decrease (75<span class="elsevierStyleHsp" style=""></span>g/l), haptoglobine decrease (0.01<span class="elsevierStyleHsp" style=""></span>g/l) and presence of schistocytes in blood smear.</p><p id="par0035" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patient 3</span>. Male, 46 years of age at the time of the second transplant, diagnosed with acute lymphoblastic leukaemia. Compatible with the diagnosis of acute lymphoblastic leukaemia ALL-L2 (FAB), Pre-B acute leukaemia (EGIL), Precursor B-cell ALL (WHO). He underwent autologous peripheral blood stem cell transplantation, with a relapse 11 months later. Six months later a second allogeneic peripheral blood hematopoietic stem cell transplantation was performed from an unrelated donor, HLA-A incompatibility, ABO-incompatible (D: A+, R: 0+). The patient began on day +32 (second transplant) with data indicating haemolysis with increased LDH levels reaching 1404<span class="elsevierStyleHsp" style=""></span>IU/l, decreased platelet count (11<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L; it required platelet support transfusion), haemoglobin decrease (90<span class="elsevierStyleHsp" style=""></span>g/l), haptoglobine decrease (0.1<span class="elsevierStyleHsp" style=""></span>g/l) and the presence of schistocytes in blood smears, without neurological or renal involvement.</p><p id="par0040" class="elsevierStylePara elsevierViewall">In all 3 cases the diagnosis was TTP, being probably cyclosporine-induced (symptoms began one week after the start of drug administration), and after applying the Karch–Lasagna<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">8</span></a> algorithm modified by Naranjo et al. a score of 5–6 was obtained (probable) for the three cases, which led to suspension of cyclosporine between days 20 and 40 after transplantation and the start of a new treatment with another immunosuppressant (tacrolimus in the 3 cases). A week after starting treatment with tacrolimus, the aforementioned parameters progressed to normal in all 3 cases.</p><p id="par0045" class="elsevierStylePara elsevierViewall">In conclusion, it seems advisable to pay special attention during the first month of treatment with cyclosporine, closely monitoring LDH, haemoglobin, haptoglobin, bilirubin and platelet count parameters, and performing ancillary tests if TTP is suspected.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Selvi Sabater P, Espuny Miró A, Rizo Cerdá AM, de la Rubia Orti JE. Púrpura trombótica trombocitopénica inducida por ciclosporina. Estudio de 3 casos. Med Clin (Barc). 2016;146:231–232.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:8 [ 0 => array:3 [ "identificador" => "bib0045" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "An acute febrile pleiochromic anemia with hyaline thrombosis of the terminals arterioles and capillaries. An undescribed disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "E. Moschcowitz" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Arch Intern Med" "fecha" => "1925" "volumen" => "36" "paginaInicial" => "89" "paginaFinal" => "93" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0050" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Morphologic diagnosis of thrombotic thrombocytopenic purpura" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "E.R. Burns" 1 => "Y. Lou" 2 => "A. Pathak" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ajh.10450" "Revista" => array:6 [ "tituloSerie" => "Am J Hematol" "fecha" => "2004" "volumen" => "75" "paginaInicial" => "18" "paginaFinal" => "21" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14695628" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0055" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cellular source of serum lactate dehydrogenase elevation in patients with thrombotic thrombocytopenic purpura" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J.A. Cohen" 1 => "M.E. Brecher" 2 => "N. Bandarenko" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Clin Apher" "fecha" => "1998" "volumen" => "13" "paginaInicial" => "16" "paginaFinal" => "19" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9590492" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0060" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Laboratory abnormalities in thrombotic thrombocytopenic purpura" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "G. Rock" 1 => "J.G. Kelton" 2 => "K.H. Shumak" 3 => "N.A. Buskard" 4 => "D.M. Sutton" 5 => "W.B. Benny" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Br J Haematol" "fecha" => "1998" "volumen" => "103" "paginaInicial" => "1031" "paginaFinal" => "1036" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9886315" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0065" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "P. Ruggenenti" 1 => "M. Noris" 2 => "G. Remuzzi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1046/j.1523-1755.2001.060003831.x" "Revista" => array:6 [ "tituloSerie" => "Kidney Int" "fecha" => "2001" "volumen" => "60" "paginaInicial" => "831" "paginaFinal" => "834" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11532079" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0070" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Ficha técnica del fármaco. Available from: <a id="intr0010" class="elsevierStyleInterRef" href="http://www.aemps.gob.es/cima/pdfs/es/ft/56799/FT_56799.pdf">http://www.aemps.gob.es/cima/pdfs/es/ft/56799/FT_56799.pdf</a> [accessed 15.05.15]." ] ] ] 6 => array:3 [ "identificador" => "bib0075" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cyclosporine A enhances platelet aggregation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.A. Grace" 1 => "M.A. Barradas" 2 => "D.P. Mikhailidis" 3 => "J.Y. Jeremy" 4 => "J.F. Moorhead" 5 => "P. Sweny" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Kidney Int" "fecha" => "1987" "volumen" => "32" "paginaInicial" => "889" "paginaFinal" => "895" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3323604" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0080" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A method for estimating the probability of adverse drug reactions" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C.A. Naranjo" 1 => "U. Busto" 2 => "E.M. Sellers" 3 => "P. Sandor" 4 => "I. Ruiz" 5 => "E.A. Roberts" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Pharmacol Ther" "fecha" => "1981" "volumen" => "30" "paginaInicial" => "239" "paginaFinal" => "245" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7249508" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000014600000005/v1_201606230528/S2387020616302303/v1_201606230528/en/main.assets" "Apartado" => array:4 [ "identificador" => "43311" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Scientific letters" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000014600000005/v1_201606230528/S2387020616302303/v1_201606230528/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020616302303?idApp=UINPBA00004N" ]
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