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392 ROBERTSON et al [46] Nesbitt IM, Goodeve AC, Guilliatt AM, et al. Characterisation of type 2N von Willebrand disease using phenotypic and molecular techniques. Thromb Haemost 1996;75:959–64. [47] Castaman G, Rodeghiero F, Tosetto A, et al. Hemorrhagic symptoms and bleeding risk in obligatory carriers of type 3 von Willebrand disease: an international, multicenter study. J Thromb Haemost 2006;4:2164–9. [48] Baronciani L, Cozzi G, Canciani MT, et al. Molecular defects in type 3 von Willebrand disease: updated results from 40 multiethnic patients. Blood Cells Mol Dis 2003;30:264–70. [49] Shelton-Inloes B, Chehab F, Mannucci P, et al. Gene deletions correlate with the development of alloantibodies in von Willebrand’s disease. J Clin Invest 1987;79:1459–65. [50] Ngo K, Glotz Trifard V, Koziol J, et al. Homozygous and heterozygous deletions of the von Willebrand factor gene in patients and carriers of severe von Willebrand disease. Proc Natl Acad Sci U S A 1988;85:2753–7. [51] Mannucci PM. Desmopressin: a nontransfusional form of treatment for congenital and acquired bleeding disorders. Blood 1988;72:1449–55. [52] Rodeghiero F, Castaman G, Di Bona E, et al. Consistency of responses to repeated DDAVP infusions in patients with von Willebrand’s disease and hemophilia A. Blood 1989;74: 1997–2000. [53] Rose EH, Aledort LM. Nasal spray desmopressin (DDAVP) for mild hemophilia A and von Willebrand disease. Ann Intern Med 1991;114:563–8. [54] Humphries JE, Siragy H. Significant hyponatremia following DDAVP administration in a healthy adult. Am J Hematol 1993;44:12–5. [55] Weinstein RE, Bona RD, Altman AJ, et al. Severe hyponatremia after repeated intravenous administration of desmopressin. Am J Hematol 1989;32:258–61. [56] Mannucci PM, Bettega D, Cattaneo M. Patterns of development of tachyphylaxis in patients with haemophilia and von Willebrand disease after repeated doses of desmopressin (DDAVP). Br J Haematol 1992;82:87–93. [57] Federici AB, Mazurier C, Berntorp E, et al. Biologic response to desmopressin in patients with severe type 1 and type 2 von Willebrand disease: results of a multicenter European study. Blood 2004;103:2032–8. [58] Haberichter SL, Balistreri M, Christopherson P, et al. Assay of the von Willebrand factor (VWF) propeptide to identify patients with type 1 von Willebrand disease with decreased VWF survival. Blood 2006;108:3344–51. [59] Fowler WE, Berkowitz LR, Roberts HR. DDAVP for type IIB von Willebrand disease. Blood 1989;74:1859–60. [60] Casonato A, Sartori MT, De Marco L, et al. 1-Desamino-8-D-arginine vasopressin (DDAVP) infusion in type IIB von Willebrand’s disease: shortening of bleeding time and induction of a variable pseudothrombocytopenia. Thromb Haemost 1990;64:117–20. [61] Mazurier C, Gaucher C, Jorieux S, et al. Biological effect of desmopressin in eight patients with type 2N (Normandy) von Willebrand disease. Br J Haematol 1994;88:849–54. [62] Rodeghiero F, Castaman G, Meyer D, et al. Replacement therapy with virus-inactivated plasma concentrates in von Willebrand disease. Vox Sang 1992;62:193–9. [63] Mannucci PM, Chediak J, Hanna W, et al. Treatment of von Willebrand disease with a highpurity factor VIII/von Willebrand factor concentrate: a prospective, multicenter study. Blood 2002;99:450–6. [64] Lillicrap D, Poon MC, Walker I, et al. Efficacy and safety of the factor VIII/von Willebrand factor concentrate, haemate-P/humate-P: ristocetin cofactor unit dosing in patients with von Willebrand disease. Thromb Haemost 2002;87:224–30. [65] Mannucci PM. Venous thromboembolism in von Willebrand disease. Thromb Haemost 2002;88:378–9. [66] Castillo R, Monteagudo J, Escolar G, et al. Hemostatic effect of normal platelet transfusion in severe von Willebrand disease patients. Blood 1991;77:1901–5.
Pediatr Clin N Am 55 (2008) 393–420 Childhood Immune Thrombocytopenic Purpura: Diagnosis and Management Victor Blanchette, FRCP a, *, Paula Bolton-Maggs, DM, FRCP b a Division of Hematology/Oncology, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada b University Department of Haematology, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, United Kingdom Immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by a low circulating platelet count caused by destruction of antibody-sensitized platelets in the reticuloendothelial system [1]. ITP can be classified based on patient age (childhood versus adult), duration of illness (acute versus chronic), and presence of an underlying disorder (primary versus secondary). Persistence of thrombocytopenia, generally defined as a platelet count of less than 150 10 9 /L for longer than 6 months, defines the chronic form of the disorder. Secondary causes of ITP include collagen vascular disorders, such as systemic lupus erythematosus (SLE); immune deficiencies, such as common variable immunodeficiency (CVID); and some chronic infections (eg, HIV and hepatitis C). This article focuses on the diagnosis and management of children (under 18 years of age) who have acute and chronic ITP. Emphasis is placed on areas of controversy and new therapies. Pathophysiology The pathophysiology of ITP increasingly is understood better (reviewed by Cines and Blanchette [1]). Not surprisingly, it is complex with involvement of many players in the human immune orchestra, including antibodies, cytokines, antigen-presenting cells, costimulatory molecules, and T and B lymphocytes (including T-helper, T-cytotoxic, and T-regulatory lymphocytes). Current knowledge is summarized later. * Corresponding author. E-mail address: victor.blanchette@sickkids.ca (V. Blanchette). 0031-3955/08/$ - see front matter Ó 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.pcl.2008.01.009 pediatric.theclinics.com
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Pediatr Clin N Am 55 (2008) xiii-xi
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Pediatr Clin N Am 55 (2008) 287-304
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DECISION ANALYSIS IN PEDIATRIC HEMA
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Nietert et al [30] Treatment of sic
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VENOUS THROMBOEMBOLISM IN CHILDREN
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PEDIATRIC ARTERIAL ISCHEMIC STROKE
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Page 94 and 95: 378 ROBERTSON et al von Willebrand
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442 FASANO & LUBAN [55,56]. This is
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444 FASANO & LUBAN [20] Roseff SD,
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THALASSEMIA UPDATE 449 hypochromia
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THALASSEMIA UPDATE 451 Fig. 1. Chan
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THALASSEMIA UPDATE 453 delivery of
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THALASSEMIA UPDATE 455 thromboses i
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THALASSEMIA UPDATE 457 On the basis
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THALASSEMIA UPDATE 459 [31] Kan YW,
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ORAL IRON CHELATORS 463 large iron-
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ORAL IRON CHELATORS 465 of 50 child
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ORAL IRON CHELATORS 467 Table 2 Com
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ORAL IRON CHELATORS 469 use in Nort
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ORAL IRON CHELATORS 473 in liver fi
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ORAL IRON CHELATORS 475 in the lowe
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ORAL IRON CHELATORS 477 Other oral
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ORAL IRON CHELATORS 479 [12] Borgna
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ORAL IRON CHELATORS 481 [55] Wonke
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HYDROXYUREA FOR CHILDREN WITH SICKL
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Fig. 1. Guideline for initiating, m
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504 TRACY & RICE congenital spheroc
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506 TRACY & RICE and antibodies aga
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508 TRACY & RICE limited splenic vo
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510 TRACY & RICE constitutes the pi
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512 TRACY & RICE German experience
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514 TRACY & RICE Table 1 Effect of
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516 TRACY & RICE decreased bilirubi
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518 TRACY & RICE [13] Bader-Meunier
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