Semin Thromb Hemost 2011; 37(7): 737-744
DOI: 10.1055/s-0031-1297164
© Thieme Medical Publishers

Pediatric Hemophilia: A Review

Roshni Kulkarni1 , J. Michael Soucie2
  • 1Department of Pediatrics and Human Development, Michigan State University, East Lansing, Michigan
  • 2Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia
Further Information

Publication History

Publication Date:
20 December 2011 (online)


The hemophilias are the most common X-linked inherited bleeding disorders, which if not properly managed can lead to chronic disease and lifelong disabilities. The challenges and issues in newborns are different from that in older children and adults. Bleeding events still predominate as the diagnostic trigger in children, however, the sites of bleeding vary with age. While delivery-associated intracranial hemorrhage (ICH), circumcision, and venipuncture bleeding are common in the newborn period, joint disease and head trauma occur in the older child and adolescent. Awareness of clinical manifestations and treatment complications are crucial in instituting appropriate management and implementing preventive strategies. Currently, inhibitors and ICH are the most challenging complications and prophylaxis is emerging as the optimal preventive care strategy.


  • 1 Soucie J M, Evatt B, Jackson D. The Hemophilia Surveillance System Project Investigators . Occurrence of hemophilia in the United States.  Am J Hematol. 1998;  59 (4) 288-294
  • 2 Tagariello G, Iorio A, Santagostino E Italian Association Hemophilia Centre (AICE) et al. Comparison of the rates of joint arthroplasty in patients with severe factor VIII and IX deficiency: an index of different clinical severity of the 2 coagulation disorders.  Blood. 2009;  114 (4) 779-784
  • 3 Soucie J M, McAlister S, McClellan A, Oakley M, Su Y. The universal data collection surveillance system for rare bleeding disorders.  Am J Prev Med. 2010;  38 (4, Suppl) S475-S481
  • 4 Kulkarni R, Soucie J M, Lusher J Haemophilia Treatment Center Network Investigators et al. Sites of initial bleeding episodes, mode of delivery and age of diagnosis in babies with haemophilia diagnosed before the age of 2 years: a report from The Centers for Disease Control and Prevention's (CDC) Universal Data Collection (UDC) project.  Haemophilia. 2009;  15 (6) 1281-1290
  • 5 World Federation of Hemophilia Report on the Annual Global Survey 2009. March 2011. Available at Accessed Oct 1, 2011
  • 6 Evatt B L. The tragic history of AIDS in the hemophilia population, 1982-1984.  J Thromb Haemost. 2006;  4 (11) 2295-2301
  • 7 Trimble S R, Parker C S, Grant A M, Soucie J M, Reyes N. Assessing emerging infectious threats to blood safety for the blood disorders community.  Am J Prev Med. 2010;  38 (4, Suppl) S468-S474
  • 8 Oldenburg J. Mutation profiling in haemophilia A.  Thromb Haemost. 2001;  85 (4) 577-579
  • 9 Bolton-Maggs P H, Pasi K J. Haemophilias A and B.  Lancet. 2003;  361 (9371) 1801-1809
  • 10 Monroe D M, Hoffman M. What does it take to make the perfect clot?.  Arterioscler Thromb Vasc Biol. 2006;  26 (1) 41-48
  • 11 Baehner R L, Strauss H S. Hemophilia in the first year of life.  N Engl J Med. 1966;  275 (10) 524-528
  • 12 Chalmers E A. Haemophilia and the newborn.  Blood Rev. 2004;  18 (2) 85-92
  • 13 Kenet G, Chan AKC, Soucie J M, Kulkarni R. Bleeding disorders in neonates.  Haemophilia. 2010;  16 (Suppl 5) 168-175
  • 14 Kulkarni R, Lusher J. Perinatal management of newborns with haemophilia.  Br J Haematol. 2001;  112 (2) 264-274
  • 15 Rodriguez V, Titapiwatanakun R, Moir C, Schmidt K A, Pruthi R K. To circumcise or not to circumcise? Circumcision in patients with bleeding disorders.  Haemophilia. 2010;  16 (2) 272-276
  • 16 Pollmann H, Richter H, Ringkamp H, Jürgens H. When are children diagnosed as having severe haemophilia and when do they start to bleed? A 10-year single-centre PUP study.  Eur J Pediatr. 1999;  158 (Suppl 3) S166-S170
  • 17 Valentino L A. Blood-induced joint disease: the pathophysiology of hemophilic arthropathy.  J Thromb Haemost. 2010;  8 (9) 1895-1902
  • 18 Manco-Johnson M J, Abshire T C, Shapiro A D et al.. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia.  N Engl J Med. 2007;  357 (6) 535-544
  • 19 Soucie J M, Cianfrini C, Janco R L et al.. Joint range-of-motion limitations among young males with hemophilia: prevalence and risk factors.  Blood. 2004;  103 (7) 2467-2473
  • 20 Beyer R, Ingerslev J, Sørensen B. Current practice in the management of muscle haematomas in patients with severe haemophilia.  Haemophilia. 2010;  16 (6) 926-931
  • 21 Nuss R, Soucie J M, Evatt B. Hemophilia Surveillance System Project Investigators . Changes in the occurrence of and risk factors for hemophilia-associated intracranial hemorrhage.  Am J Hematol. 2001;  68 (1) 37-42
  • 22 Stieltjes N, Calvez T, Demiguel V French ICH Study Group et al. Intracranial haemorrhages in French haemophilia patients (1991-2001): clinical presentation, management and prognosis factors for death.  Haemophilia. 2005;  11 (5) 452-458
  • 23 Ljung R C. Intracranial haemorrhage in haemophilia A and B.  Br J Haematol. 2008;  140 (4) 378-384
  • 24 Kulkarni R, Lusher J M. Intracranial and extracranial hemorrhages in newborns with hemophilia: a review of the literature.  J Pediatr Hematol Oncol. 1999;  21 (4) 289-295
  • 25 Gupta S N, Kechli A M, Kanamalla U S. Intracranial hemorrhage in term newborns: management and outcomes.  Pediatr Neurol. 2009;  40 (1) 1-12
  • 26 Nakar C, Cooper D L, DiMichele D. Recombinant activated factor VII safety and efficacy in the treatment of cranial haemorrhage in patients with congenital haemophilia with inhibitors: an analysis of the Hemophilia and Thrombosis Research Society Registry (2004-2008).  Haemophilia. 2010;  16 (4) 625-631
  • 27 Ljung R. The optimal mode of delivery for the haemophilia carrier expecting an affected infant is vaginal delivery.  Haemophilia. 2010;  16 (3) 415-419
  • 28 James A H, Hoots K. The optimal mode of delivery for the haemophilia carrier expecting an affected infant is caesarean delivery.  Haemophilia. 2010;  16 (3) 420-424
  • 29 Looney C B, Smith J K, Merck L H et al.. Intracranial hemorrhage in asymptomatic neonates: prevalence on MR images and relationship to obstetric and neonatal risk factors.  Radiology. 2007;  242 (2) 535-541
  • 30 Smith A R, Leonard N, Kurth M H. Intracranial hemorrhage in newborns with hemophilia: the role of screening radiologic studies in the first 7 days of life.  J Pediatr Hematol Oncol. 2008;  30 (1) 81-84
  • 31 Wilson D A, Nelson Jr M D, Fenstermacher M J The Hemophilia Growth and Development Study Group et al. Brain abnormalities in male children and adolescents with hemophilia: detection with MR imaging.  Radiology. 1992;  185 (2) 553-558
  • 32 Nelson Jr M D, Maeder M A, Usner D et al.. Prevalence and incidence of intracranial haemorrhage in a population of children with haemophilia. The Hemophilia Growth and Development Study.  Haemophilia. 1999;  5 (5) 306-312
  • 33 Eyster M E, Gill F M, Blatt P M, Hilgartner M W, Ballard J O, Kinney T R. Central nervous system bleeding in hemophiliacs.  Blood. 1978;  51 (6) 1179-1188
  • 34 Gouw S C, van der Bom J G, Marijke van den Berg H. Treatment-related risk factors of inhibitor development in previously untreated patients with hemophilia A: the CANAL cohort study.  Blood. 2007;  109 (11) 4648-4654
  • 35 Chambost H. Assessing risk factors: prevention of inhibitors in haemophilia.  Haemophilia. 2010;  16 (Suppl 2) 10-15
  • 36 Kempton C L, White II G C. How we treat a hemophilia A patient with a factor VIII inhibitor.  Blood. 2009;  113 (1) 11-17
  • 37 Verbruggen B, van Heerde W L, Laros-van Gorkom B A. Improvements in factor VIII inhibitor detection: from Bethesda to Nijmegen.  Semin Thromb Hemost. 2009;  35 (8) 752-759
  • 38 Chitlur M, Warrier I, Rajpurkar M, Lusher J M. Inhibitors in factor IX deficiency a report of the ISTH-SSC international FIX inhibitor registry (1997-2006).  Haemophilia. 2009;  15 (5) 1027-1031
  • 39 DiMichele D. Inhibitors to factor VIII/IX: immune tolerance. In: Lee C, Berntorp E, Hoots K, eds. Textbook of Hemophilia. UK: Wiley-Blackwell; 2010: 66-74
  • 40 Valentino L A, Kawji M, Grygotis M. Venous access in the management of hemophilia.  Blood Rev. 2011;  25 (1) 11-15
  • 41 Usner D W, Donfield S M, Sirois P A, Gomperts E D, Bale Jr J F, Mitchell W G. Hemophilia morbidity, cognitive functioning, and academic achievement.  J Pediatr. 1998;  133 (6) 782-787
  • 42 Shapiro A D, Donfield S M, Lynn H S Academic Achievement in Children with Hemophilia Study Group et al. Defining the impact of hemophilia: the Academic Achievement in Children with Hemophilia Study.  Pediatrics. 2001;  108 (6) E105
  • 43 Spencer M L, Wodrich D L, Schultz W, Wagner L, Recht M. Inattention, hyperactivity-impulsivity, academic skills and psychopathology in boys with and without haemophilia.  Haemophilia. 2009;  15 (3) 701-706
  • 44 Bladen M, Khair K, Liesner R, Main E. Long-term consequences of intracranial haemorrhage in children with haemophilia.  Haemophilia. 2009;  15 (1) 184-192
  • 45 MASAC recommendations concerning products licensed for the treatment of hemophilia and other bleeding disorders. MASAC document #195. 2010. The National. New York: National Hemophilia Foundation 116 West 32nd Street, New York, NY 10001 [Available at]
  • 46 Batorova A, Martinowitz U. Continuous infusion of coagulation factors: current opinion.  Curr Opin Hematol. 2006;  13 (5) 308-315
  • 47 Morfini M. Secondary prophylaxis with factor IX concentrates: continuous infusion.  Blood Transfus. 2008;  6 (Suppl 2) s21-s25
  • 48 Kulkarni R, Chitlur M, Lusher J. Treatment of congenital coagulopathies. In: Mintz P D, ed. Transfusion Therapy: Clinical Principles and Practice. 3rd ed. Bethesda, MD: AABB Press; 2011: 167-208
  • 49 Feldman B M, Pai M, Rivard G E Association of Hemophilia Clinic Directors of Canada Prophylaxis Study Group et al. Tailored prophylaxis in severe hemophilia A: interim results from the first 5 years of the Canadian Hemophilia Primary Prophylaxis Study.  J Thromb Haemost. 2006;  4 (6) 1228-1236
  • 50 Ljung R. Prophylactic therapy in haemophilia.  Blood Rev. 2009;  23 (6) 267-274
  • 51 Auerswald G, Bidlingmaier C, Kurnik K. Early prophylaxis/FVIII tolerization regimen that avoids immunological danger signals is still effective in minimizing FVIII inhibitor developments in previously untreated patients—long-term follow-up and continuing experience. Haemophilia.  2011 [Epub ahead of print]

Roshni KulkarniM.D. 

Professor and Director, Pediatric & Adolescent Hematology/Oncology; Director (Pediatrics), MSU Centers for Bleeding and Clotting Disorders; Former Director and Distinguished Hematology Consultant, Division of Blood Disorders

CDC, B 216 Clinical Center; Department of Pediatrics and Human Development, Michigan State University, East Lansing, MI 48824