{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:37:09Z","timestamp":1787240229893,"version":"build-2736575974"},"reference-count":43,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Diagnosis and management of congenital and acquired bleeding disorders in children requires not only an understanding of the unique characteristics of pediatric hemostasis but also the natural course of bleeding disorders in children, which may differ substantially from the course observed in adult patients. In this article, three bleeding disorders of great importance to the pediatric hematologist are reviewed: neonatal alloimmune thrombocytopenia (NAIT), hemophilia and immune-mediated thrombocytopenic purpura (ITP). Current aspects of management are outlined. The unique physiology of transplacental transfer of maternally derived anti-platelet antibodies can result in neonatal immune thrombocytopenia, a significant cause of morbidity and mortality from bleeding in affected infants. For patients with hemophilia, approaches to treatment have shifted over the past decade from on-demand therapy to prophylaxis, either primary of secondary, resulting in delay of onset or complete avoidance of hemophilic arthropathy. Hemophilic inhibitors often develop in young children, prompting the need for a thorough understanding of the use of bypassing agents as well as immune tolerance induction in the young child. Finally, although several management strategies for ITP of childhood have been shown to improve the platelet count, side effects associated with corticosteroids, IVIg, anti-D and splenectomy force the practitioner to also consider the option of carefully observing, but not treating, the child with ITP.<\/jats:p>","DOI":"10.1182\/asheducation-2005.1.416","type":"journal-article","created":{"date-parts":[[2005,11,22]],"date-time":"2005-11-22T20:29:34Z","timestamp":1132691374000},"page":"416-422","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":7,"title":["Management of Bleeding Disorders in Children"],"prefix":"10.1182","volume":"2005","author":[{"given":"Catherine S.","family":"Manno","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2019111703212705500_R1","doi-asserted-by":"crossref","unstructured":"Andrew M, Vegh P, Johnston M, et al. Maturation of the Hemostatic System During Childhood. Blood. 1992;80:1998\u20131905.","DOI":"10.1182\/blood.V80.8.1998.1998"},{"key":"2019111703212705500_R2","doi-asserted-by":"crossref","unstructured":"Dreyfus M, Kaplan C, Verdy E, et al. Frequency of immune thrombocytopenia in newborns: a prospective study. Blood. 1997;89:4402\u20134406.","DOI":"10.1182\/blood.V89.12.4402"},{"key":"2019111703212705500_R3","doi-asserted-by":"crossref","unstructured":"Williamson L, Hackett G, Rennie J, et al. The natural history of fetomaternal alloimmunization to the platelet-specific antigen HPA-1 (PlA1, Zwa) as determined by antenatal screening. Blood. 1998;92:2280\u20132287.","DOI":"10.1182\/blood.V92.7.2280"},{"key":"2019111703212705500_R4","doi-asserted-by":"crossref","unstructured":"Panzer S AL, Cechova E, Fischer G, et al. Maternal alloimmunization against fetal platelet antigens: a prospective study. Br J Haematol. 1995;9:655\u2013660.","DOI":"10.1111\/j.1365-2141.1995.tb05597.x"},{"key":"2019111703212705500_R5","doi-asserted-by":"crossref","unstructured":"Giovangrandi Y, Daffos F, Kaplan C, et al. Very early intracranial hemorrhage in alloimmune fetal thrombocytopenia. Lancet. 1990;336:310.","DOI":"10.1016\/0140-6736(90)91842-X"},{"key":"2019111703212705500_R6","doi-asserted-by":"crossref","unstructured":"Mueller-Eckhardt C, Kiefel V, Grubert A, et al. 348 cases of suspected neonatal alloimmune thrombocytopenia. Lancet. 1989;18:363\u2013366.","DOI":"10.1016\/S0140-6736(89)91733-9"},{"key":"2019111703212705500_R7","doi-asserted-by":"crossref","unstructured":"Glade-Bender J, McFarland J, Kaplan C, et al. Anti-HPA-3A induces severe neonatal alloimmune thrombocytopenia. J Pediatr. 2001;138:862\u2013867.","DOI":"10.1067\/mpd.2001.114029"},{"key":"2019111703212705500_R8","unstructured":"Shibata Y, Matsuda I, Miyahi T, et al. Yuka, a new platelet antigen system involved in two cases of neonatal alloimmune thrombocytopenia. Vox Sang. 1986;50:177\u2013180."},{"key":"2019111703212705500_R9","doi-asserted-by":"crossref","unstructured":"Rousseau J, Goldman M, David M. HPA-5b (Bra) neonatal alloimmune thrombocytopenia in Quebec: incidence and clinical outcomes in 31 cases. Transfusion. 2004;44:844\u2013848.","DOI":"10.1111\/j.1537-2995.2004.03304.x"},{"key":"2019111703212705500_R10","doi-asserted-by":"crossref","unstructured":"McFarland J. Detection and identification of platelet antibodies in clinical disorders. Transfusion Apheresis Sci. 2003;28:297\u2013305.","DOI":"10.1016\/S1473-0502(03)00049-1"},{"key":"2019111703212705500_R11","doi-asserted-by":"crossref","unstructured":"Bussel J. Alloimmune thrombocytopenia in the fetus and newborn. Semin Hematol. 2001;27:245\u2013252.","DOI":"10.1055\/s-2001-15254"},{"key":"2019111703212705500_R12","doi-asserted-by":"crossref","unstructured":"Soucie J, Evatt B, Jackson D, at al. Occurrence of hemophilia in the United States. Am J Hematol. 1998;59:288\u2013294.","DOI":"10.1002\/(SICI)1096-8652(199812)59:4<288::AID-AJH4>3.0.CO;2-I"},{"key":"2019111703212705500_R13","doi-asserted-by":"crossref","unstructured":"Kulkarni R, Lusher J. Perinatal management of newborns with hemophilia. Br J Haematol. 2001;112:264\u2013274.","DOI":"10.1046\/j.1365-2141.2001.02362.x"},{"key":"2019111703212705500_R14","doi-asserted-by":"crossref","unstructured":"Gitschier J, Wood W, Goralka T, et al. Characterization of the factor VIII gene. Nature. 1985;312:326\u2013330.","DOI":"10.1038\/312326a0"},{"key":"2019111703212705500_R15","doi-asserted-by":"crossref","unstructured":"Naylor J, Brinke A, Hassock S, et al. 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