%0 Journal Article %J Blood Transfus %D 2017 %T Diagnosis and management of newly diagnosed childhood autoimmune haemolytic anaemia. Recommendations from the Red Cell Study Group of the Paediatric Haemato-Oncology Italian Association. %A Ladogana, Saverio %A Maruzzi, Matteo %A Samperi, Piera %A Perrotta, Silverio %A Del Vecchio, Giovanni C %A Notarangelo, Lucia D %A Farruggia, Piero %A Verzegnassi, Federico %A Masera, Nicoletta %A Saracco, Paola %A Fasoli, Silvia %A Miano, Maurizio %A Girelli, Gabriella %A Barcellini, Wilma %A Zanella, Alberto %A Russo, Giovanna %K Anemia, Hemolytic, Autoimmune %K Blood Transfusion %K Child %K Coombs Test %K Disease Management %K Hematology %K Humans %K Immunoglobulin M %K Italy %K Pediatrics %K Societies, Medical %K Steroids %X

Autoimmune haemolytic anaemia is an uncommon disorder to which paediatric haematology centres take a variety of diagnostic and therapeutic approaches. The Red Cell Working Group of the Italian Association of Paediatric Onco-haematology (Associazione Italiana di Ematologia ed Oncologia Pediatrica, AIEOP) developed this document in order to collate expert opinions on the management of newly diagnosed childhood autoimmune haemolytic anaemia.The diagnostic process includes the direct and indirect antiglobulin tests; recommendations are given regarding further diagnostic tests, specifically in the cases that the direct and indirect antiglobulin tests are negative. Clear-cut definitions of clinical response are stated. Specific recommendations for treatment include: dosage of steroid therapy and tapering modality for warm autoimmune haemolytic anaemia; the choice of rituximab as first-line therapy for the rare primary transfusion-dependent cold autoimmune haemolytic anaemia; the indications for supportive therapy; the need for switching to second-line therapy. Each statement is provided with a score expressing the level of appropriateness and the agreement among participants.

%B Blood Transfus %V 15 %P 259-267 %8 2017 May %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/28151390?dopt=Abstract %R 10.2450/2016.0072-16 %0 Journal Article %J Br J Haematol %D 2015 %T Are all cases of paediatric essential thrombocythaemia really myeloproliferative neoplasms? Analysis of a large cohort. %A Randi, Maria L %A Geranio, Giulia %A Bertozzi, Irene %A Micalizzi, Concetta %A Ramenghi, Ugo %A Tucci, Fabio %A Notarangelo, Lucia D %A Ladogana, Saverio %A Menna, Giuseppe %A Giordano, Paola %A Consarino, Caterina %A Farruggia, Piero %A Zanazzo, Giulio A %A Fiori, Giovanni M %A Burnelli, Roberta %A Russo, Giovanna %A Jankovich, Momcilo %A Peroni, Edoardo %A Duner, Elena %A Basso, Giuseppe %A Fabris, Fabrizio %A Putti, Maria C %K Adolescent %K Adult %K Amino Acid Substitution %K Child %K Child, Preschool %K Cohort Studies %K Female %K Hematologic Neoplasms %K Humans %K Infant %K Janus Kinase 2 %K Male %K Mutation, Missense %K Neoplasm Proteins %K Thrombocythemia, Essential %X

Sporadic essential thrombocythaemia (ET) is rare in paediatrics, and the diagnostic and clinical approach to paediatric cases cannot be simply copied from experience with adults. Here, we assessed 89 children with a clinical diagnosis of ET and found that 23 patients (25·8%) had a clonal disease. The JAK2 V617F mutation was identified in 14 children, 1 child had the MPL W515L mutation, and 6 had CALR mutations. The monoclonal X-chromosome inactivation pattern was seen in six patients (two with JAK2 V617F and two with CALR mutations). The other 66 patients (74·2%) had persistent thrombocytosis with no clonality. There were no clinical or haematological differences between the clonal and non-clonal patients. The relative proportion of ET-specific mutations in the clonal children was much the same as in adults. The higher prevalence of non-clonal cases suggests that some patients may not have myeloproliferative neoplasms, with significant implications for their treatment.

%B Br J Haematol %V 169 %P 584-9 %8 2015 May %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/25716342?dopt=Abstract %R 10.1111/bjh.13329 %0 Journal Article %J Haematologica %D 2014 %T Analysis of 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia. %A Noris, Patrizia %A Schlegel, Nicole %A Klersy, Catherine %A Heller, Paula G %A Civaschi, Elisa %A Pujol-Moix, Núria %A Fabris, Fabrizio %A Favier, Rémi %A Gresele, Paolo %A Latger-Cannard, Véronique %A Cuker, Adam %A Nurden, Paquita %A Greinacher, Andreas %A Cattaneo, Marco %A De Candia, Erica %A Pecci, Alessandro %A Hurtaud-Roux, Marie-Françoise %A Glembotsky, Ana C %A Muñiz-Diaz, Eduardo %A Randi, Maria Luigia %A Trillot, Nathalie %A Bury, Loredana %A Lecompte, Thomas %A Marconi, Caterina %A Savoia, Anna %A Balduini, Carlo L %A Bayart, Sophie %A Bauters, Anne %A Benabdallah-Guedira, Schéhérazade %A Boehlen, Françoise %A Borg, Jeanne-Yvonne %A Bottega, Roberta %A Bussel, James %A De Rocco, Daniela %A de Maistre, Emmanuel %A Faleschini, Michela %A Falcinelli, Emanuela %A Ferrari, Silvia %A Ferster, Alina %A Fierro, Tiziana %A Fleury, Dominique %A Fontana, Pierre %A James, Chloé %A Lanza, Francois %A Le Cam Duchez, Véronique %A Loffredo, Giuseppe %A Magini, Pamela %A Martin-Coignard, Dominique %A Menard, Fanny %A Mercier, Sandra %A Mezzasoma, Annamaria %A Minuz, Pietro %A Nichele, Ilaria %A Notarangelo, Lucia D %A Pippucci, Tommaso %A Podda, Gian Marco %A Pouymayou, Catherine %A Rigouzzo, Agnes %A Royer, Bruno %A Sie, Pierre %A Siguret, Virginie %A Trichet, Catherine %A Tucci, Alessandra %A Saposnik, Béatrice %A Veneri, Dino %K Adult %K Female %K Humans %K Infant, Newborn %K Pregnancy %K Pregnancy Complications, Hematologic %K Retrospective Studies %K Thrombocytopenia %K Young Adult %X

Pregnancy in women with inherited thrombocytopenias is a major matter of concern as both the mothers and the newborns are potentially at risk of bleeding. However, medical management of this condition cannot be based on evidence because of the lack of consistent information in the literature. To advance knowledge on this matter, we performed a multicentric, retrospective study evaluating 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia. Neither the degree of thrombocytopenia nor the severity of bleeding tendency worsened during pregnancy and the course of pregnancy did not differ from that of healthy subjects in terms of miscarriages, fetal bleeding and pre-term births. The degree of thrombocytopenia in the babies was similar to that in the mother. Only 7 of 156 affected newborns had delivery-related bleeding, but 2 of them died of cerebral hemorrhage. The frequency of delivery-related maternal bleeding ranged from 6.8% to 14.2% depending on the definition of abnormal blood loss, suggesting that the risk of abnormal blood loss was increased with respect to the general population. However, no mother died or had to undergo hysterectomy to arrest bleeding. The search for parameters predicting delivery-related bleeding in the mother suggested that hemorrhages requiring blood transfusion were more frequent in women with history of severe bleedings before pregnancy and with platelet count at delivery below 50 × 10(9)/L.

%B Haematologica %V 99 %P 1387-94 %8 2014 Aug %G eng %N 8 %1 http://www.ncbi.nlm.nih.gov/pubmed/24763399?dopt=Abstract %R 10.3324/haematol.2014.105924 %0 Journal Article %J Clin Immunol %D 2011 %T Clinical heterogeneity and diagnostic delay of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome. %A Mazza, Cinzia %A Buzi, Fabio %A Ortolani, Federica %A Vitali, Alberto %A Notarangelo, Lucia D %A Weber, Giovanna %A Bacchetta, Rosa %A Soresina, Annarosa %A Lougaris, Vassilios %A Greggio, Nella A %A Taddio, Andrea %A Pasic, Srdjan %A de Vroede, Monique %A Pac, Malgorzata %A Kilic, Sara Sebnem %A Ozden, Sanal %A Rusconi, Roberto %A Martino, Silvana %A Capalbo, Donatella %A Salerno, Mariacarolina %A Pignata, Claudio %A Radetti, Giorgio %A Maggiore, Giuseppe %A Plebani, Alessandro %A Notarangelo, Luigi D %A Badolato, Raffaele %K Adolescent %K Adult %K Child %K Child, Preschool %K Heterozygote %K Homozygote %K Humans %K Middle Aged %K Mutation %K Polyendocrinopathies, Autoimmune %K Time Factors %K Young Adult %X

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive organ-specific autoimmune disorder that is characterized by a variable combination of (i) chronic mucocutaneous candidiasis, (ii) polyendocrinopathy and/or hepatitis and (iii) dystrophy of the dental enamel and nails. We analyzed the AIRE (autoimmune regulator) gene in subjects who presented any symptom that has been associated with APECED, including candidiasis and autoimmune endocrinopathy. We observed that 83.3% of patients presented at least two of the three typical manifestations of APECED, while the remaining 16.7% of patients showed other signs of the disease. Analysis of the genetic diagnosis of these subjects revealed that a considerable delay occurs in the majority of patients between the appearance of symptoms and the diagnosis. Overall, the mean diagnostic delay in our patients was 10.2 years. These results suggest that molecular analysis of AIRE should be performed in patients with relapsing mucocutaneous candidiasis for early identification of APECED.

%B Clin Immunol %V 139 %P 6-11 %8 2011 Apr %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/21295522?dopt=Abstract %R 10.1016/j.clim.2010.12.021 %0 Journal Article %J Blood %D 2011 %T Mutations in ANKRD26 are responsible for a frequent form of inherited thrombocytopenia: analysis of 78 patients from 21 families. %A Noris, Patrizia %A Perrotta, Silverio %A Seri, Marco %A Pecci, Alessandro %A Gnan, Chiara %A Loffredo, Giuseppe %A Pujol-Moix, Núria %A Zecca, Marco %A Scognamiglio, Francesca %A De Rocco, Daniela %A Punzo, Francesca %A Melazzini, Federica %A Scianguetta, Saverio %A Casale, Maddalena %A Marconi, Caterina %A Pippucci, Tommaso %A Amendola, Giovanni %A Notarangelo, Lucia D %A Klersy, Catherine %A Civaschi, Elisa %A Balduini, Carlo L %A Savoia, Anna %K Adolescent %K Adult %K Aged %K Aged, 80 and over %K Ankyrin Repeat %K Child %K Cohort Studies %K Family %K Female %K Gene Frequency %K Humans %K Inheritance Patterns %K Male %K Middle Aged %K Mutation %K Pedigree %K Thrombocytopenia %K Transcription Factors %K Young Adult %X

Until recently, thrombocytopenia 2 (THC2) was considered an exceedingly rare form of autosomal dominant thrombocytopenia and only 2 families were known. However, we recently identified mutations in the 5'-untranslated region of the ANKRD26 gene in 9 THC2 families. Here we report on 12 additional pedigrees with ANKRD26 mutations, 6 of which are new. Because THC2 affected 21 of the 210 families in our database, it has to be considered one of the less rare forms of inherited thrombocytopenia. Analysis of all 21 families with ANKRD26 mutations identified to date revealed that thrombocytopenia and bleeding tendency were usually mild. Nearly all patients had no platelet macrocytosis, and this characteristic distinguishes THC2 from most other forms of inherited thrombocytopenia. In the majority of cases, platelets were deficient in glycoprotein Ia and α-granules, whereas in vitro platelet aggregation was normal. Bone marrow examination and serum thrombopoietin levels suggested that thrombocytopenia was derived from dysmegakaryopoiesis. Unexplained high values of hemoglobin and leukocytes were observed in a few cases. An unexpected finding that warrants further investigation was a high incidence of acute leukemia. Given the scarcity of distinctive characteristics, the ANKRD26-related thrombocytopenia has to be taken into consideration in the differential diagnosis of isolated thrombocytopenias.

%B Blood %V 117 %P 6673-80 %8 2011 Jun 16 %G eng %N 24 %1 http://www.ncbi.nlm.nih.gov/pubmed/21467542?dopt=Abstract %R 10.1182/blood-2011-02-336537