Guidelines On Neonatal Screening And Painful Vaso-occlusive Crisis In Sickle Cell Disease: Associação Brasileira De Hematologia, Hemoterapia E Terapia Celular. Project Guidelines: Associação Médica Brasileira - 2016.

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Guidelines On Beta-thalassemia Major – Regular Blood Transfusion Therapy: Associação Brasileira De Hematologia, Hemoterapia E Terapia Celular: Project Guidelines: Associação Médica Brasileira – 2016

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Report of a ‘consensus’ on the lines of therapy for primary immune thrombocytopenia in adults, promoted by the Italian Gruppo di Studio delle Piastrine

Despite the publication in 2009 of a paper on \u2018terms and definitions of immune thrombocytopenia\u2019 (ITP), some unresolved issues remain and are reflected by the disagreement in the treatment suggested for primary ITP in adults. Considering that these disagreements could be ascribed to non-shared goals, we generated a \u2018consensus\u2019 on some terms, definitions, and assertions useful for classifying the different lines of treatment for primary ITP in adults according to their indications and goals. Agreement on the appropriateness of the single assertions was obtained by consensus for the following indicators: 1. classification of four \u2018lines of therapy\u2019; 2. acceptance of the expression \u2018sequences of disease\u2019 for the indications of the respective four lines of treatment; 3I. practicability of splenectomy; 3Ib. acceptance, with only some exceptions, of a \u2018timing for elective splenectomy of 12 months\u2019; and 4a-d. \u2018goals of the four lines of therapy.\u2019 On the basis of the consensus, a classification of four lines of treatment for primary ITP in adults was produced. In our opinion, this classification, whose validity is not influenced by the recently published new guidelines of the American Society of Hematology (ASH) and reviews, could reduce the disagreement that still exists regarding the treatment of the disease

Brazilian Thalassemia Association Protocol For Iron Chelation Therapy In Patients Under Regular Transfusion

In the absence of an iron chelating agent, patients with beta-thalassemia on regular transfusions present complications of transfusion-related iron overload. Without iron chelation therapy, heart disease is the major cause of death; however, hepatic and endocrine complications also occur. Currently there are three iron chelating agents available for continuous use in patients with thalassemia on regular transfusions (desferrioxamine, deferiprone, and deferasirox) providing good results in reducing cardiac, hepatic and endocrine toxicity. These practice guidelines, prepared by the Scientific Committee of Associação Brasileira de Thalassemia (ABRASTA), presents a review of the literature regarding iron overload assessment (by imaging and laboratory exams) and the role of T2* magnetic resonance imaging (MRI) to control iron overload and iron chelation therapy, with evidence-based recommendations for each clinical situation. Based on this review, the authors propose an iron chelation protocol for patients with thalassemia under regular transfusions.356428434Borgna-Pignatti, C., Rugolotto, S., de Stefano, P., Zhao, H., Cappellini, M.D., Del Vecchio, G.C., Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine (2004) Haematologica, 89 (10), pp. 1187-1193. , Comment in: Haematologica. 2004;89(10):1157-9Cunningham, M.J., Macklin, E.A., Neufeld, E.J., Cohen, A.R., Thalassemia Clinical Research Network. Complications of beta-thalassemia major in North America (2004) Blood, 104 (1), pp. 34-39Kirk, P., Roughton, M., Porter, J.B., Walker, J.M., Tanner, M.A., Patel, J., Cardiac T2* magnetic resonance for prediction of cardiac complications in thalassemia major (2009) Circulation, 120 (20), pp. 1961-1968. , Comment in: Circulation. 2009;120(20):1937-9Brittenham, G.M., Griffith, P.M., Nienhuis, A.W., McLaren, C.E., Young, N.S., Tucker, E.E., Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major (1994) N Engl J Med, 331 (9), pp. 567-573. , Comment in: N Engl J Med. 1995;332(4):270-1. N Engl J Med. 1995;332(4):271-2. N Engl J Med. 1994;331(9):609-10Olivieri, N.F., Nathan, D.G., Macmillan, J.H., Wayne, A.S., Liu, P.P., McGee, A., Survival in medically treated patients with homozygous beta-thalassemia (1994) N Engl J Med, 331 (9), pp. 574-578. , Comment in: N Engl J Med. 1995;332(4):271author reply 272-3N Engl J Med. 1995;332(4):271-2author reply 272-3N Engl J Med. 1994331(9):609-10Gabutti, V., Piga, A., Results of long-term iron-chelating therapy (1996) Acta Haematol, 95 (1), pp. 26-36Modell, B., Khan, M., Darlison, M., Survival in beta-thalassaemia major in the UK: Data from the UK Thalassaemia Register (2000) Lancet, 355 (9220), pp. 2051-2052Anderson, L.J., Westwood, M.A., Prescott, E., Walker, J.M., Pennell, D.J., Wonke, B., Development of thalassaemic iron overload cardiomyopathy despite low liver iron levels and meticulous compliance to desferrioxamine (2006) Acta Haematol, 115 (1-2), pp. 106-108Hoffbrand, A.V., Cohen, A., Hershko, C., Role of deferiprone in chelation therapy for transfusional iron overload (2003) Blood, 102 (1), pp. 17-24Victor Hoffbrand, A., Deferiprone therapy for transfusional iron overload (2005) Best Pract Res Clin Haematol, 18 (2), pp. 299-317Wonke, B., Wright, C., Hoffbrand, A.V., Combined therapy with deferiprone and desferrioxamine (1998) Br J Haematol, 103 (2), pp. 361-364. , Comment in: Br J Haematol. 1999;106(1):252-3Mourad, F.H., Hoffbrand, A.V., Sheikh-Taha, M., Koussa, S., Khoriaty, A.I., Taher, A., Comparison between desferrioxamine and combined therapy with desferrioxamine and deferiprone in iron overloaded thalassaemia patients (2003) Br J Haematol, 121 (1), pp. 187-189Kattamis, A., Kassou, C., Berdousi, H., Ladis, V., Papassotiriou, I., Kattamis, C., Combined therapy with desferrioxamine and deferiprone in thalassemic patients: Effect on urinary iron excretion (2003) Haematologica, 88 (12), pp. 1423-1425Wu, K.H., Chang, J.S., Tsai, C.H., Peng, C.T., Combined therapy with deferiprone and desferrioxamine successfully regresses severe heart failure in patients with beta-thalassemia major (2004) Ann Hematol, 83 (7), pp. 471-473Alymara, V., Bourantas, D., Chaidos, A., Bouranta, P., Gouva, M., Vassou, A., Effectiveness and safety of combined iron-chelation therapy with deferoxamine and deferiprone (2004) Hematol J, 5 (6), pp. 475-479Origa, R., Bina, P., Agus, A., Crobu, G., Defraia, E., Dessi, C., Combined therapy with deferiprone and desferrioxamine in thalassemia major (2005) Haematologica, 90 (10), pp. 1309-1314. , Comment in: Haematologica. 2005;90(10):1297ADaar, S., Pathare, A.V., Combined therapy with desferrioxamine and deferiprone in beta thalassemia major patients with transfusional iron overload (2006) Ann Hematol, 85 (5), pp. 315-319Kattamis, A., Ladis, V., Berdousi, H., Kelekis, N.L., Alexopoulou, E., Papasotiriou, I., Iron chelation treatment with combined therapy with deferiprone and deferioxamine: A 12-month trial (2006) Blood Cells Mol Dis, 36 (1), pp. 21-25Piga, A., Gaglioti, C., Fogliacco, E., Tricta, F., Comparative effects of deferiprone and deferoxamine on survival and cardiac disease in patients with thalassemia major: A retrospective analysis (2003) Haematologica, 88 (5), pp. 489-496. , Comment in: Haematologica. 2003;88(5):481-2Borgna-Pignatti, C., Cappellini, M.D., de Stefano, P., Del Vecchio, G.C., Forni, G.L., Gamberini, M.R., Cardiac morbidity and mortality in deferoxamine- or deferiprone-treated patients with thalassemia major (2006) Blood, 107 (9), pp. 3733-3737Pennell, D.J., Berdoukas, V., Karagiorga, M., Ladis, V., Piga, A., Aessopos, A., Randomized controlled trial of deferiprone or desferoxamine in beta-thalassemia major patients with asymptomatic myocardial siderosis (2006) Blood, 107 (9), pp. 3738-3744Tanner, M.A., Galanello, R., Dessi, C., Smith, G.C., Westwood, M.A., Agus, A., A randomized, placebo-controlled, double-blind trial of the effect of combined therapy with deferoxamine and deferiprone on myocardial iron in thalassemia major using cardiovascular magnetic resonance (2007) Circulation, 115 (14), pp. 1876-1884Tsironi, M., Deftereos, S., Andriopoulos, P., Farmakis, D., Meletis, J., Aessopos, A., Reversal of heart failure in thalassemia major by combined chelation therapy: A case report (2005) Eur J Haematol, 74 (1), pp. 84-85Davis, B.A., Porter, J.B., Long-term outcome of continuous 24-hour deferoxamine infusion via indwelling intravenous catheters in high-risk beta-thalassemia (2000) Blood, 95 (4), pp. 1229-1236Neufeld, E.J., Oral chelators deferasirox and deferiprone for transfusional iron overload in thalassemia major: New data, new questions (2006) Blood, 107 (9), pp. 3436-3441Cappellini, M.D., Cohen, A., Piga, A., Bejaoui, M., Perrotta, S., Agaoglu, L., A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia (2006) Blood, 107 (9), pp. 3455-3462. , Comment in: Blood. 2006;108(5):1775-6Blood. 2006;108(2):774-5Blood. 2006;108(2):778Deugnier, Y., Turlin, B., Ropert, M., Cappellini, M.D., Porter, J.B., Giannone, V., Improvement in liver pathology of patients with β-thalassemia treated with deferasirox for at least 3 years (2011) Gastroenterology, 141 (4). , Comment in: Gastroenterology. 2011;141(4):1142-3 1202-1211+1211.e1-3Cappellini, M.D., Bejaoui, M., Agaoglu, L., Canatan, D., Capra, M., Cohen, A., Iron chelation with deferasirox in adult and pediatric patients with thalassemia major: Efficacy and safety during 5 years' follow-up (2011) Blood, 118 (4), pp. 884-893Eleftheriou, P., Tanner, M., Pennel, D., Porter, J.B., Response of myocardial T2* to oral deferasirox monotherapy for 1 year in 29 patients with transfusion-dependent anaemiasa subgroup analysis (2006) Haematologica, 91, p. 366Pennell, D.J., Porter, J.B., Cappellini, M.D., El-Beshlawy, A., Chan, L.L., Aydinok, Y., Efficacy of deferasirox in reducing and preventing cardiac iron overload in beta-thalassemia (2010) Blood, 115 (12), pp. 2364-2371. , Comment in: Blood. 2010;115(12):2333-4Pennell, D.J., Porter, J.B., Cappellini, M.D., Chan, L.L., El-Beshlawy, A., Aydinok, Y., Continued improvement in myocardial T2* over two years of deferasirox therapy in β-thalassemia major patients with cardiac iron overload (2011) Haematologica, 96 (1), pp. 48-54. , Comment in: Haematologica. 2011;96(1):5-8Pennell, D.J., Porter, J.B., Cappellini, M.D., Chan, L.L., El-Beshlawy, A., Aydinok, Y., Deferasirox for up to 3 years leads to continued improvement of myocardial T2* in patients with β-thalassemia major (2012) Haematologica, 97 (6), pp. 842-848De Assis, R.A., Ribeiro, A.A., Kay, F.U., Rosemberg, L.A., Nomura, C.H., Loggetto, S.R., Pancreatic iron stores assessed by magnetic resonance imaging (MRI) in beta thalassemic patients (2012) Eur J Radiol, 81 (7), pp. 1465-1470Wood, J.C., Tyszka, J.M., Carson, S., Nelson, M.D., Coates, T.D., Myocardial iron loading in transfusion-dependent thalassemia and sickle cell disease (2004) Blood, 103 (5), pp. 1934-1936Wood, J.C., Origa, R., Agus, A., Matta, G., Coates, T.D., Galanello, R., Onset of cardiac iron loading in pediatric patients with thalassemia major (2008) Haematologica, 93 (6), pp. 917-920. , Comment in: Haematologica. 2009;94(12):1776-7Fernandes, J.L., Fabron Jr., A., Verissimo, M., Early cardiac iron overload in children with transfusion-dependent anemias (2009) Haematologica, 94 (12), pp. 1776-1777. , Comment on: Haematologica. 2008;93(6):917-20Harrison, P.M., Arosio, P., The ferritins: Molecular properties, iron storage function and cellular regulation (1996) Biochim Biophys Acta, 1275 (3), pp. 161-203Olivieri, N.F., Brittenham, G.M., Matsui, D., Berkovitch, M., Blendis, L.M., Cameron, R.G., Iron-chelation therapy with oral deferiprone in patients with thalassemia major (1995) N Engl J Med, 332 (14), pp. 918-922. , Comment in: N Engl J Med. 1995;333(9):597-8N Engl J Med. 1995;333(9):598N Engl J Med. 1995;332(14):953-4Hershko, C., Link, G., Cabantchik, I., Pathophysiology of iron overload (1998) Ann N Y Acad Sci, 850, pp. 191-201Wood, J.C., Enriquez, C., Ghugre, N., Tyzka, J.M., Carson, S., Nelson, M.D., Coates, T.D., MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients (2005) Blood, 106 (4), pp. 1460-1465Cappellini, M.D., Cohen, A., Eleftheriou, A., Piga, A., Porter, J., Taher, A., (2008) Guidelines For the Clinical Management of Thalassaemia [Internet], , http://www.thalassaemia.org.cy/wordpress/wp-content/uploads/2012/12/Guidelines-2nd-edition-revised-ENGLISH-lo.pdf, editors, 2nd rev ed. Cyprus: Thalassaemia International Federation, [cited 2011 Sep 21]. Available fromAnderson, L.J., Holden, S., Davis, B., Prescott, E., Charrier, C.C., Bunce, N.H., Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload (2001) Eur Heart J, 22 (23), pp. 2171-2179. , Comment in: Eur Heart J. 2001;22(23):2140-1Ghugre, N.R., Enriquez, C.M., Coates, T.D., Nelson Jr., M.D., Wood, J.C., Improved R2* measurements in myocardial iron overload (2006) J Magn Reson Imaging, 23 (1), pp. 9-16Fernandes, J.L., Sampaio, E.F., Verissimo, M., Pereira, F.B., da Silva, J.A., Figueiredo, G.S., Heart and liver T2* assessment for iron overload using different software programs (2011) Eur Radiol, 21 (12), pp. 2503-2510Hankins, J.S., McCarville, M.B., Loeffler, R.B., Smeltzer, M.P., Onciu, M., Hoffer, F.A., R2* magnetic resonance imaging of the liver in patients with iron overload (2009) Blood, 113 (20), pp. 4853-4855Carpenter, J.P., He, T., Kirk, P., Roughton, M., Anderson, L.J., Noronha, S.V., On T2* magnetic resonance and cardiac iron (2011) Circulation, 123 (14), pp. 1519-1528Farmaki, K., Tzoumari, I., Pappa, C., Chouliaras, G., Berdoukas, V., Normalisation of total body iron load with very intensive combined chelation reverses cardiac and endocrine complications of thalassaemia major (2010) Br J Haematol, 148 (3), pp. 466-475. , Comment in: Br J Haematol. 2010;150(4):489-90Porter, J.B., Piga, A., Cohen, A., Ford, J.M., Bodner, J., Rojkjaer, L., Safety of deferasirox (Exjade®) in patients with transfusion-dependent anemias and iron overload who achieve serum ferritin levels < 1000 ng/mL during long-term treatment (2008) Blood, 112 (11). , http://abstracts.hematologylibrary.org/cgi/content/abstract/112/11/5423?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=piga+a&searchid=1&FIRSTINDEX=0&volume=112&issue=11&resourcetype=HWCIT, (ASH Annual Meeting Abstracts) [Internet], abstract 5423. [cited 2012 Mar 21], Available fromCohen, A.R., Galanello, R., Piga, A., de Sanctis, V., Tricta, F., Safety and effectiveness of long-term therapy with the oral iron chelator deferiprone (2003) Blood, 102 (5), pp. 1583-1587Al-Refaie, F.N., Wonke, B., Hoffbrand, A.V., Deferiprone-associated myelotoxicity (1994) Eur J Haematol, 53 (5), pp. 298-301(2011) Projeto Diretrizes: Associação Médica Brasileira E Conselho Federal De Medicina, , http://www.projetodiretrizes.org.br/projeto_diretrizes/texto_introdutorio.pdf, São Paulo, [cited, Sep 14], Available fromFargion, S., Fracanzani, A.L., Rossini, A., Borzio, M., Riggio, O., Belloni, G., Iron reduction and sustained response to interferon-alpha therapy in patients with chronic hepatitis C: Results of an Italian multicenter randomized study (2002) Am J Gastroenterol, 97 (5), pp. 1204-1210. , Comment in: Am J Gastroenterol. 2002;97(5):1093-6Angelucci, E., Muretto, P., Nicolucci, A., Baronciani, D., Erer, B., Gaziev, J., Effects of iron overload and hepatitis C virus positivity in determining progression of liver fibrosis in thalassemia following bone marrow transplantation (2002) Blood, 100 (1), pp. 17-21Hershko, C., Pathogenesis and management of iron toxicity in thalassemia (2010) Ann N Y Acad Sci, 1202, pp. 1-9Piga, A., Longo, F., Duca, L., Roggero, S., Vinciguerra, T., Calabrese, R., High non transferrin bound iron levels and heart disease in thalassemia major (2009) Am J Hematol, 84 (1), pp. 29-33Farmaki, K., Tzoumari, I., Pappa, C., Oral chelators in transfusion-dependent thalassemia major patients may prevent or reverse iron overload complications (2011) Blood Cells Mol Dis, 47 (1), pp. 33-4

A randomized trial of amlodipine in addition to standard chelation therapy in patients with thalassemia major

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Cardiovascular disease resulting from iron accumulation is still a major cause of death in patients with thalassemia major (TM). Voltage-gated calcium-channel blockade prevents iron entry into cardiomyocytes and may provide an adjuvant treatment to chelation, reducing myocardial iron uptake. We evaluated whether addition of amlodipine to chelation strategies would reduce myocardial iron overload in TM patients compared with placebo. In a multicenter, double-blind, randomized, placebo-controlled trial, 62 patients were allocated to receive oral amlodipine 5 mg/day or placebo in addition to their current chelation regimen. The main outcome was change in myocardial iron concentration (MIC) determined by magnetic resonance imaging at 12 months, with patients stratified into reduction or prevention groups according to their initial T2* below or above the normal human threshold of 35 ms (MIC, 0.59 mg/g dry weight). At 12 months, patients in the reduction group receiving amlodipine (n = 15) had a significant decrease in MIC compared with patients receiving placebo (n 5 15) with a median of -0.26 mg/g (95% confidence interval, -1.02 to -0.01) vs 0.01 mg/g (95% confidence interval, -0.13 to 0.23), P = .02. No significant changes were observed in the prevention group (treatment-effect interaction with P = .005). The same findings were observed in the subgroup of patients with T2* <20 ms. Amlodipine treatment did not cause any serious adverse events. Thus, in TM patients with cardiac siderosis, amlodipine combined with chelation therapy reduced cardiac iron more effectively than chelation therapy alone. Because this conclusion is based on subgroup analyses, it needs to be confirmed in ad hoc clinical trials. This trial was registered at www.clinicaltrials.gov identifier as #NCT01395199.Cardiovascular disease resulting from iron accumulation is still a major cause of death in patients with thalassemia major (TM). Voltage-gated calcium-channel blockade prevents iron entry into cardiomyocytes and may provide an adjuvant treatment to chelat1281215551561FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)sem informaçãoCardiovascular disease resulting from iron accumulation is still a major cause of death in patients with thalassemia major (TM). Voltage-gated calcium-channel blockade prevents iron entry into cardiomyocytes and may provide an adjuvant treatment to chela