Camperdown Hemoglobin Associated With β° Thalassemia In A Brazilian Child

We report the coexistence of Hb Camperdown [β 104 (G6) Arg → Ser] and β°-thalassemia [β39 (Gln → stop codon)] in a nine-month-old Brazilian boy. He had a relatively more severe hypochromic and microcytic anemia in comparison to his mother's β-thalassemia trait. His Hb Camperdown heterozygous father was clinically and hematologically normal. To our knowledge, this is the first description of an association of β°-thalassemia with Hb Camperdown. Copyright by the Brazilian Society of Genetics.283394396Araújo, A.S., Silva, W.A., Leao, S.A., Bandeira, F.C., Petrou, M., Modell, B., Zago, M.A., A different molecular pattern of β-thalassemia mutations in Northeast of Brazil (2003) Hemoglobin, 27, pp. 211-217Amone, A., X-ray diffraction study of binding of 2,3-diphosphoglycerate to human deoxyhemoglobin (1972) Nature, 237, pp. 146-149Bertuzzo, C.S., Sonati, M.F., Costa, F.F., Hematological phenotype and the type of β thalassemia mutation in Brazil (1997) Braz J Genet, 20, pp. 319-321Bianco, I., Graziani, B., Carboni, C., Genetic patterns in thalassemia intermedia (constitutional microcytic anemia). Familial hematological and biosynthetic studies (1977) Hum Hered, 27, pp. 257-272Blouquit, Y., Lacombe, C., Arous, N., Le Qurrec, A., Branconnier, F., Bonhomme, J., Soummer, A.M., Galacteros, F., Seven new cases of hemoglobin Camperdown alpha 2 beta 2 104 (G6) ARG → SER found in Malta, Sicily and Tunisia (1984) Hemoglobin, 8, pp. 613-619Chang, J.C., Kan, Y.W., β°-thalassemia, a nonsense mutation in man (1979) Proc Natl Acad Sci USA, 76, pp. 2886-2889Clarke, G.M., Higgins, T.N., Laboratory investigation of hemoglobinopathies and thalassemias: Review and update (2000) Clin Chem, 46, pp. 1284-1290Fonseca, S.F., Kerbauy, J., Escrivçao, C., Figueiredo, M.S., Cançado, R., Arruda, V.R., Saad, S.T.O., Costa, F.F., Genetic analysis of beta-thalassemia major and beta-thalassemia intermedia in Brazil (1998) Hemoglobin, 22, pp. 197-207Grignoli, C.R.E., Carvalho, M.H., Kimura, E.M., Sonati, M.F., Arruda, V.R., Saad, S.T.O., Costa, F.F., β°-thalassemia resulting from a novel mutation: β66/u → stop codon (2000) Eur J Haematol, 64, pp. 137-138Kimura, E.M., Grignoli, C.R.E., Pinheiro, V.R.P., Costa, F.F., Sonati, M.F., Thalassemia intermedia as a result of heterozygosis for β°-thallassemia and αααanti3.7/αα genotype in a Brazilian patient (2003) Braz J Med Biol Res, 36, pp. 699-701Kister, J., Barbadjian, J., Blouquit, Y., Bohn, B., Galacteros, F., Poyart, C., Inhibition of oxygen-linked anion binding in Hb Camperdown [α2β2 104 (G6) ARG → SER] (1989) Hemoglobin, 13, pp. 567-578Miranda, S.R.P., Kimura, E.M., Teixeira, R.C., Bertuzzo, C.S., Ramalho, A.A., Saad, S.T.O., Costa, F.F., Hb Camperdown [α2β2 104 (G6) ARG → SER] identified by DNA analysis in a Brazilian family (1996) Hemoglobin, 20, pp. 147-153Old, J.M., Screening arid genetic diagnosis of haemoglobin disorders (2003) Blood Rev, 17, pp. 43-53Olivieri, N.F., The β-thalassemias (1999) N Engl J Med, 341, pp. 99-109Thein, S.L., Genetic insights into the clinical diversity of beta thalassaemia (2004) Br J Haematol, 124, pp. 264-274Weatherall, D.J., Clegg, J.B., Inherited haemoglobin disorders: An increasing global health problem (2001) Bull World Health Organ, 79, pp. 704-712Wilkinson, T., Chua, C.G., Carrell, R.W., Robin, H., Exner, T., Lee, K.M., Kronenberg, H., Haemoglobin Camperdown β 104(G6) Arginine leads to serine (1975) Biochim Biophys Acta, 393, pp. 195-200Zago, M.A., Costa, F.F., Hereditary hemoglobin disorders in Brazil (1985) Trans R Soc Trop Med Hyg, 79, pp. 385-38

Diagnosis And Treatment Of Congenital Hemophilia With Inhibitors. A Latin American Perspective

The Committee of Latin America on the Therapeutics of Inhibitor Groups (CLOTTING) is composed of a number of hemophilia specialists from Latin America. The group aims to encourage the adoption of a good standard of care for Latin American patients with hemophilia. The occurrence of inhibitors in patients with hemophilia poses clinical challenges, and it is estimated that between 1 000 and 3 000 patients in Latin America are affected by hemophilia with inhibitors. There is an urgent need to establish a regional consensus and clinical guidelines for the diagnosis and treatment of these patients. We present an extensive review based on best current clinical practice and published literature, as seen from a Latin American perspective, taking into account the variable nature of hemophilia care available in the various countries in this Region.683227242Ehrenforth, S., Kreuz, W., Scharrer, I., Incidence of development of factor VIII and factor IX inhibitors in haemophiliacs (1992) Lancet, 339, pp. 594-598Katz, J., Prevalence of factor IX inhibitors among patients with haemophilia B: Results of a large-scale North American study (1996) Haemophilia, 2, pp. 28-31Goudemand, J., Pharmaco-economic aspects of inhibitor treatment (1998) Eur J Haematol, 61, pp. 24-27World Hemophilia Federation Report on Global Survey 2006. World Federation of Hemophilia, 2007. On www.wfh.orgconsulted on 23/04/2008Rieger, A., Roisenberg, I., Prevalence of factor VIII inhibitors in patients with hemophilia A in Brazil (1999) Thromb Haemost, 81, pp. 475-476Fontes, E.M., Amorim, L., Carvalho, S.M., Farah, M.B., Hemophilia care in the state of Rio de Janeiro, Brazil (2003) Rev Panam Salud Pública, 13, pp. 124-128Izquierdo-Ramírez, J., Contreras-Mulato, E.L., Sotelo-Ham, E.I., Incidence of inhibitors in children with hemophilia A (1988) Bol Med Hosp Infant Méx, 45, pp. 578-582Boadas, A., Ruiz-Sáez, A., Arguello, A., de Bosch, N., Prevalence and acute bleeding treatment of allo and auto FVIII and FIX antibodies cases in Venezuela (2004) Haemophilia, 10, p. 56Wight, J., Paisley, S., The epidemiology of inhibitors in hemophilia A: A systematic review (2003) Haemophilia, 9, pp. 418-435Delivery of treatment for hemophilia (2002) Report of a joint WHO/WFH/ISTH meeting, , World Health OrganizationHay, C.R., Brown, S., Collins, P.W., Keeling, D.M., Liesner, R., The diagnosis and management of factor VIII and IX inhibitors: A guideline from the United Kingdom Haemophilia Centre Doctors Organization (2006) Br J Haematol, 133, pp. 591-605Ewing, N.P., Kasper, C.K., In vitro detection of mild inhibitors to factor VIII in hemophilia (1982) Am J Clin Pathol, 77, pp. 749-752Verbruggen, B., Novakova, I., Wessels, H., Boezeman, J., van den Berg, M., Mauser-Bunschoten, E., The Nijmegen modification of the Bethesda assay for factor VIII:C inhibitors: Improved specificity and reliability (1995) Thromb Haemost, 73, pp. 247-251Giles, A.R., Verbruggen, B., Rivard, G.E., Teitel, J., Walker, I., A detailed comparison of the performance of the standard versus the Nijmegen modification of the Bethesda assay in detecting factor VIII:C inhibitors in the hemophilia A population of Canada. Association of Hemophilia Centre Directors of Canada. Factor VIII/IX Subcommittee of Scientific and Standardization Committee of International Society on Thrombosis and Haemostasis (1998) Thromb Haemost, 79, pp. 872-875Verbruggen, B., van Heerde, W., Novakova, I., Lillicrap, D., Giles, A., A 4% solution of bovine serum albumin may be used in place of factor VIII:C deficient plasma in the control sample in the Nijmegen modification of the Bethesda factor VIII:C inhibitor assay (2002) Thromb Haemost, 88, pp. 362-364White II, G.C., Rosendaal, F., Aledort, L.M., Lusher, J.M., Rothschild, C., Ingerslev, J., Definitions in hemophilia. Recommendation of the scientific subcommittee on factor VIII and factor IX of the scientific and standardization committee of the International Society on Thrombosis and Haemostasis (2001) Thromb Haemost, 85, p. 560Kitchen, S., McCraw, A., (2000) Diagnosis of hemophilia and other bleeding disorders, , A laboratory manual. World Federation of Hemophiliahttp://www.med.unc.edu/isth, Available at:, Accessed November 2005http://www.wfh.org, Available at:, Accessed November 2005Oldenburg, J., Brackmann, H.H., Schwaab, R., Risk factors for inhibitor development in hemophilia A (2000) Haematologica, 85, pp. 7-13Rossetti, L.C., Candela, M., Pérez Bianco, R., de Tezanos Pinto, M., Western, A., Goodeve, A., Analysis of factor VIII gene intron 1 inversion in Argentinean families with severe hemophilia A and a review of the literature (2004) Blood Coagul Fibrinolysis, 15, pp. 569-572Santos, A., Montalva, O., Thomas, S., Veiga, M., De Paula, E., Ozelo, M., Genetic and ethnic aspects related to the development of inhibitors among Brazilian patients with hemophilia from five distinct geographical regions in Brazil (2006) Haemophilia, 12, pp. 1-154Mantilla-Capacho, J.M., Beltrán-Miranda, C.P., Luna-Záizar, H., Frequency of intron 1 and 22 inversions of Factor VIII gene in Mexican patients with severe Hemophilia A (2007) Am J Hematol, 82, pp. 283-287Guidelines for the management of hemophilia. World Federation of Hemophilia, 2005Girolami, A., Luzzatto, G., Varvarikis, C., Pellati, D., Sartori, R., Girolami, B., Main clinical manifestations of a bleeding diathesis: An often disregarded aspect of medical and surgical history taking (2005) Haemophilia, 11, pp. 193-202Suggestions for the management of FVIII inhibitors (2000) Treatment of Hemophilia Monograph, , Inhibitor Subcommittee of the Association of Hemophilia Clinic Directors of Canada, revised edition, World Federation of HemophiliaKasper, C., Diagnosis and management of inhibitors to factors VIII and IX (2004) Treatment of Hemophilia Monograph, , World Federation of HemophiliaGringeri, A., Mannucci, P.M., Italian Association of Haemophilia Centres. Italian guidelines for the diagnosis and treatment of patients with hemophilia and inhibitors (2005) Haemophilia, 11, pp. 611-619Key, N.S., Aledort, L.M., Beardsley, D., Home treatment of mild to moderate bleeding episodes using recombinant factor VIIa (NovoSeven) in haemophiliacs with inhibitors (1998) Thromb Haemost, 80, pp. 912-918Ingerslev, J., Sneppen, O., Hvid, I., Fredberg, U., Kristensen, H.L., Sindet-Petersen, S., Treatment of acute bleeding episodes with rFVIIa (1999) Vox Sang, 77, pp. 42-46Santagostino, E., Gringeri, A., Mannucci, P.M., Home treatment with recombinant activated factor VII in patients with factor VIII inhibitors: The advantages of early intervention (1999) Br J Haematol, 104, pp. 22-26Negrier, C., Goudemand, J., Sultan, Y., Bertrand, M., Rothschild, C., Lauroua, P., Multicenter retrospective study on the utilization of FEIBA in France in patients with factor VIII and factor IX inhibitors. French FEIBA Study Group. Factor Eight Bypassing Activity (1997) Thromb Haemost, 77, pp. 1113-1119Astermark, J., Donfield, S.M., DiMichelle, D.M., A randomized comparison of bypassing agents in hemophilia complicated by an inhibitor - The Feiba® NovoSeven® Comparative Study (FENOC) (2007) Blood, 109, pp. 546-551Young, G., Shafer, F.E., Rojas, P., Seremetis, S., Single 270 μg kg-1 dose rFVIIa vs. standard 90 μg kg-1 dose rFVIIa and APCC for home treatment of joint bleeds in hemophilia patients with inhibitors: A randomized comparison (2008) Haemophilia, 14, pp. 287-294Ozelo, M.C., Villaça, P.R., De Almeida, J.O., A cost evaluation of treatment alternatives for mild-to-moderate bleeding episodes in patients with hemophilia and inhibitors in Brazil (2007) Haemophilia, 13, pp. 462-469Kenet, G., Lubetsky, A., Luboshitz, J., Martinowitz, U., A new approach to treatment of bleeding episodes in young hemophilia patients: A single bolus megadose of recombinant activated factor VII (NovoSeven) (2003) J Thromb Haemost, 1, pp. 450-455Parameswaran, R., Shapiro, A.D., Gill, J.C., Kessler, C.M., Dose effect and efficacy of rFVIIa in the treatment of hemophilia patients with inhibitors: Analysis from the Hemophilia and Thrombosis Research Society Registry (2005) Haemophilia, 11, pp. 100-106Kavakli, K., Makris, M., Zulfikar, B., Erhardtsen, E., Abrams, Z.S., Kenet, G., Home treatment of haemarthroses using single dose regimen of recombinant activated factor VII in patients with hemophilia and inhibitors. A multi-centre, randomized, double blind, cross-over trial (2006) Thromb Haemost, 95, pp. 600-605Santagostino, E., Mancuso, M.E., Rocino, A., Mancuso, G., Scaraggi, F., Mannucci, P.M., A prospective randomized trial of high and standard dosages of recombinant factor VIIa for treatment of haemarthroses in hemophiliacs with inhibitors (2006) J Thromb Haemost, 4, pp. 367-371Schneiderman, J., Nugent, D.J., Young, G., Sequential therapy with activated prothrombin complex concentrate and recombinant factor VIIa in patients with severe hemophilia and inhibitors (2004) Haemophilia, 10, pp. 347-351Lusher, J.M., Shapiro, S.S., Palascak, J.E., Rao, A.V., Levine, P.H., Blatt, P.M., Efficacy of prothrombin-complex concentrates in hemophiliacs with antibodies to factor VIII: A multicenter therapeutic trial (1980) NEJM, 303, pp. 421-425Teitel, J., Berntorp, E., Collins, P., A systematic approach to controlling problem bleeds in patients with severe congenital hemophilia A and high-titre inhibitors (2007) Haemophilia, 13, pp. 256-263Lloyd Jones, M., Wight, J., Paisley, S., Knight, C., Control of bleeding in patients with hemophilia A with inhibitors: A systematic review (2003) Haemophilia, 9, pp. 464-520Ewenstein, B.M., Takemoto, C., Warrier, I., Nephrotic syndrome as a complication of immune tolerance in hemophilia B (1997) Blood, 89, pp. 1115-1116Warrier, I., Lenk, H., Saidi, P., Pollmann, H., Tengborn, L., Berntorp, E., Nephrotic syndrome in hemophilia B patients with inhibitors (1998) Haemophilia, 4, p. 248Warrier, I., Management of hemophilia B patients with inhibitors and anaphylaxis (1998) Haemophilia, 4, pp. 574-576Strawczynski, H., Stachewitsch, A., Morgenstern, G., Shaw, M.E., Delivery of care to hemophilic children: Home care versus hospitalization (1973) Pediatrics, 51, pp. 986-991Rabiner, S.F., Telfer, M.C., Fajardo, R., Home transfusions of hemophiliacs (1972) JAMA, 221, pp. 885-887Levine, P., The home therapy program at the New England area hemophilia center (1977) Scand J Haematol, 31, pp. 37-51Soucie, J.M., Symons, J.I., Evatt, B., Brettler, D., Huszti, H., Linden, J., Home-based factor infusion therapy and hospitalization for bleeding complications among males with hemophilia (2001) Haemophilia, 7, pp. 198-206Solovieva, S., Clinical severity of disease, functional disability and health-related quality of life. Three-year follow-up study of 150 Finnish patients with coagulation disorders (2001) Haemophilia, 7, pp. 53-63Teitel, J.M., Barnard, D., Israels, S., Lillicrap, D., Poon, M.C., Sek, J., Home management of hemophilia (2004) Haemophilia, 10, pp. 118-133Ingerslev, J., Thykjær, H., Scheibel, E., Approaches towards successful home treatment in patients with inhibitors (1998) Eur J Haematol, 61, pp. 11-14Young, G., McDaniel, M., Nugent, D.J., Prophylactic recombinant factor VIIa in hemophilia patients with inhibitors (2005) Haemophilia, 11, pp. 203-207Saxon, B.R., Shanks, D., Jory, C.B., Williams, V., Effective prophylaxis with daily recombinant factor VIIa (rFVIIa-Novoseven) in a child with high titre inhibitors and a target joint (2001) Thromb Haemost, 86, pp. 1126-1127Konkle, B.A., Ebbesen, L.S., Erhardtsen, E., Randomized, prospective clinical trial of recombinant factor VIIa for secondary prophylaxis in hemophilia patients with inhibitors (2007) J Thromb Haemost, 5, pp. 1904-1913Hoots, W.K., Ebbesen, L.S., Konkle, B.A., Secondary prophylaxis with recombinant activated factor VII improves health-related quality of life of hemophilia patients with inhibitors (2008) Haemophilia, 14, pp. 466-475Leissinger, C.A., Prevention of bleeds in hemophilia patients with inhibitors: Emerging data and clinical direction (2004) Am J Hematol, 77, pp. 187-193Luu, H., Ewenstein, B., FEIBA safety profile in multiple modes of clinical and home-therapy application (2004) Haemophilia, 10, pp. 10-16Leissinger, C.A., Becton, D.L., Ewing, N.P., Valentino, L.A., Prophylactic treatment with activated prothrombin complex concentrate (FEIBA) reduces the frequency of bleeding episodes in paediatric patients with hemophilia A and inhibitors (2007) Haemophilia, 13, pp. 249-255Villar, A., Aronis, S., Morfini, M., Pharmacokinetics of activated recombinant coagulation factor VII (NovoSeven®) in children vs. adults with hemophilia A (2004) Haemophilia, 10, pp. 352-359Klitgaard, T., Nielsen, T.G., Overview of the human pharmacokinetics of recombinant activated factor VII (2008) Br J Clin Pharmacol, 65, pp. 3-11Rodriguez-Merchan, E.C., Rocino, A., Ewenstein, B., Consensus perspectives on surgery in hemophilia patients with inhibitors: Summary statement (2004) Haemophilia, 10, pp. 50-52Hilgartner, M.W., Factor replacement therapy (1989) Hemophilia in the Child and Adults, pp. 1-26. , Hilgartner MW, Pochedly C eds, New York, Raven Press Ltd(2000) Oxford Textbook of Surgery, , Morris PJ, Wood WG eds, 2nd edition. Oxford, Oxford University PressRickard, K.A., Guidelines for therapy and optimal dosages of coagulation factors for treatment of bleeding and surgery in hemophilia (1995) Haemophilia, 1, pp. 8-13Shapiro, A., Gilchrist, G.S., Hoots, W.K., Cooper, H.A., Gastineau, D.A., Prospective, randomised trial of two doses of rFVIIa (NovoSeven) in hemophilia patients with inhibitors undergoing surgery (1998) Thromb Haemost, 80, pp. 773-778Hvid, I., Rodriguez-Merchan, E.C., Orthopaedic surgery in haemophilic patients with inhibitors: An overview (2002) Haemophilia, 8, pp. 288-291Rodriguez-Merchan, E.C., Rocino, A., Literature review of surgery management in inhibitor patients (2004) Haemophilia, 10, pp. 22-29Abshire, T., Kenet, G., Recombinant factor VIIa: Review of efficacy, dosing regimens and safety in patients with congenital and acquired factor VIII or IX inhibitors (2004) J Thromb Haemost, 2, pp. 899-909Ingerslev, J., Efficacy and safety of Recombinant Factor VIIa in the prophylaxis of bleeding in various surgical procedures in hemophilic patients with factor VIII and factor IX inhibitors (2000) Semin Thromb Hemost, 26, pp. 425-432Tjønnfjord, G.E., Brinch, L., Gedde-Dahl III, T., Brosstad, F.R., Activated prothrombin complex concentrate (FEIBA) treatment during surgery in patients with inhibitors to FVIII/IX (2004) Haemophilia, 10, pp. 174-178Ingerslev, J., Sorensen, B., Role of recombinant activated factor VII as hemostatic support in orthopedic surgery (2006) TATM, 8, pp. 35-42Obergfell, A., Auvinen, M.K., Mathew, P., Recombinant activated factor VII for haemophilia patients with inhibitors undergoing orthopaedic surgery: A review of the literature (2008) Haemophilia, 14, pp. 233-241Ewenstein, B.M., Valentino, L.A., Journeycake, J.M., Consensus recommendations for use of central venous access devices in hemophilia (2004) Haemophilia, 10, pp. 629-648Morado, M., Jimenez-Yuste, V., Villar, A., Complications of central venous catheters in patients with hemophilia and inhibitors (2001) Haemophilia, 7, pp. 551-556Bollard, C.M., Teague, L.R., Berry, E.W., Ockelford, P.A., The use of central venous catheters (portacaths) in children with hemophilia (2000) Haemophilia, 6, pp. 66-70O'Connell, N., Mc Mahon, C., Smith, J., Recombinant factor VIIa in the management of surgery and acute bleeding episodes in children with hemophilia and high responding inhibitors (2002) Br J Haematol, 116, pp. 632-635Cooper, H.A., Jones, C.P., Campion, E., Roberts, H.R., Hedner, U., Rationale for the use of high dose rFVIIa in a high-titre inhibitor patient with hemophilia B during major orthopaedic procedures (2001) Haemophilia, 7, pp. 517-522Colowick, A.B., Bohn, R.L., Avorn, J., Ewenstein, B.M., Immune tolerance induction in hemophilia patients with inhibitors: Costly can be cheaper (2000) Blood, 96, pp. 1698-1702Brackmann, H.H., Gormsen, J., Massive factor-VIII infusion in haemophiliac with factor-VIII inhibitor, high responder (1977) Lancet, 2, p. 933Key, N.S., Inhibitors in congenital coagulation disorders (2004) Br J Haematol, 127, pp. 379-391Nilsson, I.M., Berntorp, E., Zettervall, O., Induction of immune tolerance in patients with hemophilia and antibodies to factor VIII by combined treatment with intravenous IgG, cyclophosphamide, and factor VIII (1988) NEJM, 318, pp. 947-950Mathias, M., Khair, K., Hann, I., Liesner, R., Rituximab in the treatment of alloimmune factor VIII and IX antibodies in two children with severe hemophilia (2004) Br J Haematol, 125, pp. 366-368Stasi, R., Brunetti, M., Stipa, E., Amadori, S., Selective B-cell depletion with rituximab for the treatment of patients with acquired hemophilia (2004) Blood, 103, pp. 4424-4428Carcao, M., Ungar, W.J., Feldman, B.M., Cost-utility analysis in evaluating prophylaxis in hemophilia (2004) Haemophilia, 10, pp. 50-57Curtin, J., Misra, A., Teo, J., Webster, B., Lammi, A., Use of Rituximab as an alternative strategy for the management of difficult high titre inhibitors in children with hemophilia A (2004) Haemophilia, 10, p. 57DiMichele, D., Immune tolerance therapy dose as an outcome predictor (2003) Haemophilia, 9, pp. 382-386Mariani, G., Kroner, B., Immune tolerance in hemophilia with factor VIII inhibitors: Predictors of success (2001) Haematologica, 86, pp. 1186-1193DiMichele, D., Inhibitors: Resolving diagnostic and therapeutic dilemmas (2002) Haemophilia, 8, pp. 280-287Lenk, H., The German Registry of immune tolerance treatment in hemophilia-1999 update (2000) Haematologica, 85, pp. 45-47Haya, S., Lopez, M.F., Aznar, J.A., Batlle, J., Immune tolerance treatment in hemophilia patients with inhibitors: The Spanish Registry (2001) Haemophilia, 7, pp. 154-159DiMichele, D.M., Hoots, W.K., Pipe, S.W., Rivard, G.E., Santagostino, E., International workshop on immune tolerance induction: Consensus recomendations (2007) Haemophilia, 13, pp. 1-22Kreuz, W., Mentzer, D., Auerswald, G., Becker, S., Joseph-Steiner, J., Successful immune tolerance therapy of FVIII inhibitor in children after changing from high to intermediate purity FVIII concentrate (1996) Haemophilia, 2, p. 19Rocino, A., Papa, M.L., Salerno, E., Capasso, F., Miraglia, E., de Biasi, R., Immune tolerance induction in hemophilia A patients with high-responding inhibitors to factor VIII: Experience at a single institution (2001) Haemophilia, 7, pp. 33-38DiMichele, D., Rivard, G., Hay, C., Antunes, S., Inhibitors in hemophilia: Clinical aspects (2004) Haemophilia, 10, pp. 140-145Mauser-Bunschoten, E.P., Nieuwenhuis, H.K., Roosendaal, G., van den Berg, H.M., Low-dose immune tolerance induction in hemophilia A patients with inhibitors (1995) Blood, 86, pp. 983-988Almeida, J., Paula, J.C., Toscano, R., Immune tolerance such as salvage therapy in severe hemophilia A patient with ultra high-responders inhibitors (2002) Haemophilia, 8, p. 538Solano, M.H., Ramírez, C., Parra, L., Tratamiento de inhibidores del factor VIII en hemofilia. (1998) Acta Med Colomb, 23, p. 193Carneiro, J.D.A., Bassit, R.P., Villaça, P.R., Sandoval, E.P.N., Silva, C.S.S.S., D'amico, E.A., Low-dose immune tolerance induction in hemophilia A children with inhibitors (2002) Haemophilia, 8, pp. 538-539Wight, J., Paisley, S., Knight, C., Immune tolerance induction in patients with hemophilia A with inhibitors: A systematic review (2003) Haemophilia, 9, pp. 436-463Tengborg, L., Hansson, S., Fasth, A., Lübeck, P.O., Berg, A., Ljung, R., Anaphylactoid reactions and nephrotic syndrome - a considerable risk during factor IX treatment in patients with hemophilia B and inhibitors: A report on the outcome in two brothers (1998) Haemophilia, 4, pp. 854-859Schulman, S., Safety, efficacy and lessons from continuous infusion with rFVIIa (1998) Haemophilia, 4, pp. 564-567Schulman, S., Continuous infusion of recombinant factor VIIa in hemophilic patients with inhibitors: Safety, monitoring, and cost effectiveness (2000) Semin Thromb Hemost, 26, pp. 421-424Pruthi, R.K., Mathew, P., Valentino, L.A., Sumner, M.J., Seremetis, S., Hoots, W.K., Haemostatic efficacy and safety of bolus and continuous infusion of recombinant factor VIIa are comparable in hemophilia patients with inhibitors undergoing major surgery. Results from an open-label, randomized, multicenter trial (2007) Thromb Haemost, 98, pp. 726-732Smith, M.P., Ludlam, C.A., Collins, P.W., Elective surgery on factor VIII inhibitor patients using continuous infusion of recombinant activated factor VII: Plasma factor VII activity of 10 IU/ml is associated with an increased incidence of bleeding (2001) Thromb Haemost, 86, pp. 949-953Santagostino, E., Morfini, M., Rocino, A., Baudo, F., Scaraggi, F.A., Gringeri, A., Relationship between factor VII activity and clinical efficacy of recombinant factor VIIa given by continuous infusion to patients with factor VIII inhibitors (2001) Thromb Haemost, 86, pp. 954-958Mauser-Bunschoten, E.P., Koopman, M.M., Goede-Bolder, A.D., Efficacy of recombinant factor VIIa administered by continuous infusion to hemophilia patients with inhibitors (2002) Haemophilia, 8, pp. 649-656Ludlam, C.A., Smith, M.P., Morfini, M., Gringeri, A., Santagostino, E., Savidge, G.F., A prospective study of recombinant activated factor VII administered by continuous infusion to inhibitor patients undergoing elective major orthopaedic surgery: A pharmacokinetic and efficacy evaluation (2003) Br J Haematol, 120, pp. 808-813Escobar, M.A., Recombinant Factor VIIa: The possibilities for monitoring (2003) TATM, 5, pp. 51-54Young, G., Ebbesen, L.S., Viuff, D., Evaluation of thromboelastography for monitoring recombinant activated factor VII ex

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A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter

Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS

We present the results of a search for new, heavy particles that decay at a significant distance from their production point into a final state containing charged hadrons in association with a high-momentum muon. The search is conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS detector operating at the Large Hadron Collider. Production of such particles is expected in various scenarios of physics beyond the standard model. We observe no signal and place limits on the production cross-section of supersymmetric particles in an R-parity-violating scenario as a function of the neutralino lifetime. Limits are presented for different squark and neutralino masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final version to appear in Physics Letters

Measurement of the inclusive isolated prompt photon cross-section in pp collisions at sqrt(s)= 7 TeV using 35 pb-1 of ATLAS data

A measurement of the differential cross-section for the inclusive production of isolated prompt photons in pp collisions at a center-of-mass energy sqrt(s) = 7 TeV is presented. The measurement covers the pseudorapidity ranges |eta|<1.37 and 1.52<=|eta|<2.37 in the transverse energy range 45<=E_T<400GeV. The results are based on an integrated luminosity of 35 pb-1, collected with the ATLAS detector at the LHC. The yields of the signal photons are measured using a data-driven technique, based on the observed distribution of the hadronic energy in a narrow cone around the photon candidate and the photon selection criteria. The results are compared with next-to-leading order perturbative QCD calculations and found to be in good agreement over four orders of magnitude in cross-section.Comment: 7 pages plus author list (18 pages total), 2 figures, 4 tables, final version published in Physics Letters