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ERROR: type should be string, got "https://profreg.medscape.com/px/getpracticeprofile.do?method=getProfessionalProfile&urlCache=aHR0cHM6Ly93d3cubWVkc2NhcGUuY29tL2Fuc3dlcnMvNzc5MzIyLTc4MTQwLzk1NTY5MC1vdmVydmlldw==\nDrugs & Diseases > Hematology > Hemophilia A Q&A\nWhich clinical history is characteristic of hemophilia A in the genitourinary tract?\nAuthor: Douglass A Drelich, MD; Chief Editor: Srikanth Nagalla, MBBS, MS, FACP more...\nIn the genitourinary tract, gross hematuria may occur in as many as 90% of patients. In the GI tract, bleeding may complicate common GI disorders. Bleeding in the CNS is the leading cause of hemorrhagic death in patients with hemophilia.\nPeyvandi F, Garagiola I, Young G. The past and future of haemophilia: diagnosis, treatments, and its complications. Lancet. 2016 Feb 17. 3:15056. [Medline].\nJones PK, Ratnoff OD. The changing prognosis of classic hemophilia (factor VIII \"deficiency\"). Ann Intern Med. 1991 Apr 15. 114(8):641-8. [Medline].\nFederici AB. The factor VIII/von Willebrand factor complex: basic and clinical issues. Haematologica. 2003 Jun. 88(6):EREP02. [Medline].\nChorba TL, Holman RC, Strine TW, Clarke MJ, Evatt BL. Changes in longevity and causes of death among persons with hemophilia A. Am J Hematol. 1994 Feb. 45(2):112-21. [Medline].\nMudad R, Kane WH. DDAVP in acquired hemophilia A: case report and review of the literature. Am J Hematol. 1993 Aug. 43(4):295-9. [Medline].\nArnold WD, Hilgartner MW. Hemophilic arthropathy. Current concepts of pathogenesis and management. J Bone Joint Surg Am. 1977 Apr. 59(3):287-305. [Medline]. [Full Text].\nPinto P, Ghosh K, Shetty S. F8 gene mutation profile in Indian hemophilia A patients: Identification of 23 novel mutations and factor VIII inhibitor risk association. Mutat Res. 2016 Feb 10. 786:27-33. [Medline].\nGouw SC, van der Bom JG, Ljung R, Escuriola C, Cid AR, et al. Factor VIII products and inhibitor development in severe hemophilia A. N Engl J Med. 2013 Jan 17. 368(3):231-9. [Medline].\nPeyvandi F, Mannucci PM, Garagiola I, El-Beshlawy A, Elalfy M, Ramanan V, et al. A Randomized Trial of Factor VIII and Neutralizing Antibodies in Hemophilia A. N Engl J Med. 2016 May 26. 374 (21):2054-64. [Medline].\nBrown T. PRAC Confirms No Difference in Risk Between Hemophilia A Drugs. Medscape Medical News. Available at https://www.medscape.com/viewarticle/885146. September 01, 2017; Accessed: September 06, 2018.\nVerbruggen 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. Thromb Haemost. 1995 Feb. 73(2):247-51. [Medline].\nKlinge J, Auerswald G, Budde U, Klose H, Kreuz W, Lenk H, et al. Detection of all anti-factor VIII antibodies in haemophilia A patients by the Bethesda assay and a more sensitive immunoprecipitation assay. Haemophilia. 2001 Jan. 7(1):26-32. [Medline].\nBitting RL, Bent S, Li Y, Kohlwes J. The prognosis and treatment of acquired hemophilia: a systematic review and meta-analysis. Blood Coagul Fibrinolysis. 2009 Oct. 20(7):517-23. [Medline].\nKazazian HH Jr, Tuddenham EGD, Antonarakis SE. Hemophilia A and parahemophilia: deficiencies of coagulation factors VIII and V. Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular bases of Inherited Disease. 7th ed. New York, NY: McGraw-Hill; 1995. 3241-67.\nRoelse JC, De Laaf RT, Timmermans SM, Peters M, Van Mourik JA, Voorberg J. Intracellular accumulation of factor VIII induced by missense mutations Arg593-->Cys and Asn618-->Ser explains cross-reacting material-reduced haemophilia A. Br J Haematol. 2000 Feb. 108(2):241-6. [Medline].\nSpreafico M, Peyvandi F. Combined Factor V and Factor VIII Deficiency. Semin Thromb Hemost. 2009 Jun. 35(4):390-9. [Medline].\nHemophilia: Data & Statistics. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/ncbddd/hemophilia/data.html. April 12, 2017; Accessed: September 6, 2018.\nShetty S, Bhave M, Ghosh K. Acquired hemophilia a: diagnosis, aetiology, clinical spectrum and treatment options. Autoimmun Rev. 2011 Apr. 10(6):311-6. [Medline].\nVenkateswaran L, Wilimas JA, Jones DJ, Nuss R. Mild hemophilia in children: prevalence, complications, and treatment. J Pediatr Hematol Oncol. 1998 Jan-Feb. 20(1):32-5. [Medline].\nDi Michele DM, Gibb C, Lefkowitz JM, Ni Q, Gerber LM, Ganguly A. Severe and moderate haemophilia A and B in US females. Haemophilia. 2014 Mar. 20(2):e136-43. [Medline].\nLoveland KA, Stehbens J, Contant C, Bordeaux JD, Sirois P, Bell TS, et al. Hemophilia growth and development study: baseline neurodevelopmental findings. J Pediatr Psychol. 1994 Apr. 19(2):223-39. [Medline].\nAnagnostis P, Karras S, Paschou SA, Goulis DG. Haemophilia A and B as a cause for secondary osteoporosis and increased fracture risk. Blood Coagul Fibrinolysis. 2015 Jun 26. [Medline].\nManco-Johnson MJ, Nuss R, Jacobson LJ. Heparin neutralization is essential for accurate measurement of factor VIII activity and inhibitor assays in blood samples drawn from implanted venous access devices. J Lab Clin Med. 2000 Jul. 136(1):74-9. [Medline].\nAbdul-Kadir R, Davies J, Halimeh S, Chi C. Advances in pregnancy management in carriers of hemophilia. J Appl Hematol [serial online] 2013 [cited 2014 May 6];4:125-30. Available at http://www.jahjournal.org/text.asp?2013/4/4/125/127894. Accessed: May 6, 2014.\nBerntorp E, Astermark J, Björkman S, Blanchette VS, Fischer K, Giangrande PL, et al. Consensus perspectives on prophylactic therapy for haemophilia: summary statement. Haemophilia. 2003 May. 9 Suppl 1:1-4. [Medline].\nLjung RC. Prophylactic infusion regimens in the management of hemophilia. Thromb Haemost. 1999 Aug. 82(2):525-30. [Medline].\nIorio A, Marchesini E, Marcucci M, Stobart K, Chan AK. Clotting factor concentrates given to prevent bleeding and bleeding-related complications in people with hemophilia A or B. Cochrane Database Syst Rev. 2011 Sep 7. 9:CD003429. [Medline].\nMiners AH, Sabin CA, Tolley KH, Lee CA. Assessing the effectiveness and cost-effectiveness of prophylaxis against bleeding in patients with severe haemophilia and severe von Willebrand's disease. J Intern Med. 1998 Dec. 244(6):515-22. [Medline].\nCoppola A, Margaglione M, Santagostino E, Rocino A, Grandone E, Mannucci PM, et al. Factor VIII gene (F8) mutations as predictors of outcome in immune tolerance induction of hemophilia A patients with high-responding inhibitors. J Thromb Haemost. 2009 Nov. 7(11):1809-15. [Medline].\nRodriguez-Merchan EC, De la Corte-Rodriguez H, Jimenez-Yuste V. Radiosynovectomy in haemophilia: long-term results of 500 procedures performed in a 38-year period. Thromb Res. 2014 Nov. 134 (5):985-90. [Medline].\nChapman WC, Singla N, Genyk Y, McNeil JW, Renkens KL Jr, Reynolds TC, et al. A phase 3, randomized, double-blind comparative study of the efficacy and safety of topical recombinant human thrombin and bovine thrombin in surgical hemostasis. J Am Coll Surg. 2007 Aug. 205(2):256-65. [Medline].\nZanon E, Martinelli F, Bacci C, Zerbinati P, Girolami A. Proposal of a standard approach to dental extraction in haemophilia patients. A case-control study with good results. Haemophilia. 2000 Sep. 6(5):533-6. [Medline].\nOldenburg J, Mahlangu JN, Kim B, Schmitt C, Callaghan MU, Young G, et al. Emicizumab Prophylaxis in Hemophilia A with Inhibitors. N Engl J Med. 2017 Aug 31. 377 (9):809-818. [Medline]. [Full Text].\nHAVEN 2 interim data. Presented at the 26th Congress of the International Society on Thrombosis and Haemostasis (ISTH) Meeting. Berlin, Germany. July 8-13, 2017.\nOldenburg J, Levy GG. Emicizumab Prophylaxis in Hemophilia A with Inhibitors. N Engl J Med. 2017 Nov 30. 377 (22):2194-2195. [Medline]. [Full Text].\nO'Connell N, Mc Mahon C, Smith J, Khair K, Hann I, Liesner R, et al. Recombinant factor VIIa in the management of surgery and acute bleeding episodes in children with haemophilia and high responding inhibitors. Br J Haematol. 2002 Mar. 116(3):632-5. [Medline].\nSiddiqui MA, Scott LJ. Recombinant factor VIIa (Eptacog Alfa): a review of its use in congenital or acquired haemophilia and other congenital bleeding disorders. Drugs. 2005. 65(8):1161-77. [Medline].\nMcQuilten ZK, Barnes C, Zatta A, Phillips LE. Off-Label Use of Recombinant Factor VIIa in Pediatric Patients. Pediatrics. 2012 Jun. 129(6):e1533-e1540. [Medline].\nvon Depka M. Immune tolerance therapy in patients with acquired hemophilia. Hematology. 2004 Aug. 9(4):245-57. [Medline].\nHay CR, DiMichele DM. The principal results of the International Immune Tolerance Study: a randomized dose comparison. Blood. 2012 Feb 9. 119(6):1335-44. [Medline]. [Full Text].\nCarcao M, St Louis J, Poon MC, Grunebaum E, Lacroix S, Stain AM, et al. Rituximab for congenital haemophiliacs with inhibitors: a Canadian experience. Haemophilia. 2006 Jan. 12(1):7-18. [Medline].\nFranchini M, Mannucci PM. Inhibitor eradication with rituximab in haemophilia: where do we stand?. Br J Haematol. 2014 Jun. 165(5):600-8. [Medline].\nAggarwal A, Grewal R, Green RJ, Boggio L, Green D, Weksler BB, et al. Rituximab for autoimmune haemophilia: a proposed treatment algorithm. Haemophilia. 2005 Jan. 11(1):13-9. [Medline].\nStachnik JM. Rituximab in the treatment of acquired hemophilia. Ann Pharmacother. 2006 Jun. 40(6):1151-7. [Medline].\nPersonal communication with Dr. Troy H. Guthrie, Jr. MD. Jacksonville, Florida: Medical Director Baptist Cancer Institute;\nHitt E. Hemophilia: contact sports pose little risk. Medscape Medical News. Available at http://www.medscape.com/viewarticle/772326. Accessed: October 16, 2012.\nLeissinger C, Gringeri A, Antmen B, Berntorp E, Biasoli C, Carpenter S, et al. Anti-inhibitor coagulant complex prophylaxis in hemophilia with inhibitors. N Engl J Med. 2011 Nov 3. 365(18):1684-92. [Medline].\nMahlangu J, Powell JS, Ragni MV, Chowdary P, Josephson NC, Pabinger I, et al. Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A. Blood. 2014 Jan 16. 123(3):317-25. [Medline]. [Full Text].\nFDA approves the first antihemophilic factor, Fc fusion protein for patients with Hemophilia A. U.S. Food and Drug Administration. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm400167.htm. Accessed: June 17, 2014.\nMahlangu J, Oldenburg J, Paz-Priel I, Negrier C, Niggli M, Mancuso ME, et al. Emicizumab Prophylaxis in Patients Who Have Hemophilia A without Inhibitors. N Engl J Med. 2018 Aug 30. 379 (9):811-822. [Medline].\nDuncan N, Kronenberger W, Roberson C, Shapiro A. VERITAS-Pro: a new measure of adherence to prophylactic regimens in haemophilia. Haemophilia. 2010 Mar. 16(2):247-55. [Medline].\nDen Uijl I, Mauser-Bunschoten EP, Roosendaal G, Schutgens R, Fischer K. Efficacy assessment of a new clotting factor concentrate in haemophilia A patients, including prophylactic treatment. Haemophilia. 2009 Nov. 15(6):1215-8. [Medline].\nIngerslev HJ, Hindkjaer J, Jespersgaard C, Lind MP, Kølvraa S. [Preimplantation genetic diagnosis. The first experiences in Denmark]. Ugeskr Laeger. 2001 Oct 1. 163(40):5525-8. [Medline].\nLissens W, Sermon K. Preimplantation genetic diagnosis: current status and new developments. Hum Reprod. 1997 Aug. 12(8):1756-61. [Medline].\nWells D, Delhanty JD. Preimplantation genetic diagnosis: applications for molecular medicine. Trends Mol Med. 2001 Jan. 7(1):23-30. [Medline].\nKumar R, Bouskill V, Schneiderman JE, Pluthero FG, Kahr WH, Craik A, et al. Impact of aerobic exercise on haemostatic indices in pediatric patients with haemophilia. Thromb Haemost. 2016 Feb 25. 115 (6):[Medline].\nChuah MK, Collen D, VandenDriessche T. Gene therapy for hemophilia. J Gene Med. 2001 Jan-Feb. 3(1):3-20. [Medline].\nMatsui H. Endothelial progenitor cell-based therapy for hemophilia A. Int J Hematol. 2012 Feb. 95(2):119-24. [Medline].\nHigh KH, Nathwani A, Spencer T, Lillicrap D. Current status of haemophilia gene therapy. Haemophilia. 2014 May. 20 Suppl 4:43-9. [Medline].\nSokal EM, Lombard C, Mazza G. Mesenchymal stem cell treatment for hemophilia: a review of current knowledge. J Thromb Haemost. 2015 Jun. 13 Suppl 1:S161-S166. [Medline].\nCastellino AM. 'Promise of a Cure': Gene Therapy for Hemophilia A. Medscape Medical News. Available at https://www.medscape.com/viewarticle/889830. December 9, 2017; Accessed: December 12, 2017.\nRangarajan S, Walsh L, Lester W, Perry D, Madan B, Laffan M, et al. AAV5-Factor VIII Gene Transfer in Severe Hemophilia A. N Engl J Med. 2017 Dec 9. 26 (1):1-16. [Medline]. [Full Text].\nRodriguez-Merchan EC, De La Corte-Rodriguez H. Radiosynovectomy in haemophilic synovitis of elbows and ankles: Is the effectiveness of yttrium-90 and rhenium-186 different?. Thromb Res. 2016 Feb 10. 140:41-45. [Medline].\n[Guideline] Hanley J, McKernan A, Creagh MD, Classey S, McLaughlin P, Goddard N, et al. Guidelines for the management of acute joint bleeds and chronic synovitis in haemophilia: A United Kingdom Haemophilia Centre Doctors' Organisation (UKHCDO) guideline. Haemophilia. 2017 Jul. 23 (4):511-520. [Medline].\nAntunes SV, Tangada S, Stasyshyn O, Mamonov V, Phillips J, Guzman-Becerra N, et al. Randomized comparison of prophylaxis and on-demand regimens with FEIBA NF in the treatment of haemophilia A and B with inhibitors. Haemophilia. 2014 Jan. 20(1):65-72. [Medline].\nBogdanova N, Markoff A, Pollmann H, Nowak-Göttl U, Eisert R, Wermes C, et al. Spectrum of molecular defects and mutation detection rate in patients with severe hemophilia A. Hum Mutat. 2005 Sep. 26(3):249-54. [Medline].\nBroderick CR, Herbert RD, Latimer J, Barnes C, Curtin JA, Mathieu E, et al. Association between physical activity and risk of bleeding in children with hemophilia. JAMA. 2012 Oct 10. 308(14):1452-9. [Medline].\nBrooks M. FDA OKs Turoctocog Alpha (NovoEight) for Hemophilia A. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/812759. Accessed: February 29, 2016.\nCastaman G, Mancuso ME, Giacomelli SH, Tosetto A, Santagostino E, Mannucci PM, et al. Molecular and phenotypic determinants of the response to desmopressin in adult patients with mild hemophilia A. J Thromb Haemost. 2009 Nov. 7(11):1824-31. [Medline].\nEwenstein BM, Wong WY, Schoppmann A. Bypassing agent prophylaxis for preventing arthropathy in patients with inhibitors. Haemophilia. 2010 Jan. 16(1):179-80. [Medline].\nKonkle BA, Kessler C, Aledort L, Andersen J, Fogarty P, Kouides P, et al. Emerging clinical concerns in the ageing haemophilia patient. Haemophilia. 2009 Nov. 15(6):1197-209. [Medline].\nTucker ME. FDA Approves Hemophilia Drug FEIBA for Bleeding Prophylaxis. Medscape Medical News. Available at http://www.medscape.com/viewarticle/818236. December 23, 2013; Accessed: September 06, 2018.\nCoagulation pathway.\nThe hemostatic pathway. APC = activated protein C (APC); AT-III = antithrombin III; FDP = fibrin degradation products; HC-II = heparin cofactor II; HMWK = high-molecular-weight kininogen; PAI = plasminogen activator inhibitor; sc-uPA = single-chain urokinase plasminogen activator; tc-uPA = two-chain urokinase plasminogen activator; TFPI = tissue factor pathway inhibitor; tPA = tissue plasminogen activator\nStructural domains of human factor VIII. Adapted from: Stoilova-McPhie S, Villoutreix BO, Mertens K, Kemball-Cook G, Holzenburg A. 3-Dimensional structure of membrane-bound coagulation factor VIII: modeling of the factor VIII heterodimer within a 3-dimensional density map derived by electron crystallography. Blood. Feb 15 2002;99(4):1215-23; Roberts HR, Hoffman M. Hemophilia A and B. In: Beutler E, Lichtman MA, Coller BS, et al, eds. Williams Hematology. 6th ed. NY: McGraw-Hill; 2001:1639-57; and Roberts HR. Thoughts on the mechanism of action of FVIIa. Presented at: Second Symposium on New Aspects of Haemophilia Treatment; 1991; Copenhagen, Denmark.\nPossible genetic outcomes in individuals carrying the hemophilic gene.\nPhotograph of a teenage boy with bleeding into his right thigh as well as both knees and ankles.\nPhotograph of the right knee in an older man with a chronically fused, extended knee following open drainage of knee bleeding that occurred many years previously.\nPhotograph depicting severe bilateral hemophilic arthropathy and muscle wasting. The 3 punctures made into the left knee joint were performed in an attempt to aspirate recent aggravated bleeding.\nRadiograph depicting advanced hemophilic arthropathy of the knee joint. These images show chronic severe arthritis, fusion, loss of cartilage, and joint space deformities.\nRadiograph depicting advanced hemophilic arthropathy of the elbow. This image shows chronic severe arthritis, fusion, loss of cartilage, and joint space deformities.\nPhotograph of a hemophilic knee at surgery, with synovial proliferation caused by repeated bleeding; synovectomy was required.\nLarge amount of vascular synovium removed at surgery.\nMicroscopic appearance of synovial proliferation and high vascularity. If stained with iron, diffuse deposits would be demonstrated; iron-laden macrophages are present.\nLarge pseudocyst involving the left proximal femur.\nTransected pseudocyst (following disarticulation of the left lower extremity due to vascular compromise, nerve damage, loss of bone, and nonfunctional limb). This photo shows black-brown old blood, residual muscle, and bone.\nDissection of a pseudocyst.\nTransected pseudocyst with chocolate brown-black old blood.\nPhotograph of a patient who presented with a slowly expanding abdominal and flank mass, as well as increasing pain, inability to eat, weight loss, and weakness of his lower extremity.\nPlain radiograph of the pelvis showing a large lytic area.\nIntravenous pyelogram showing extreme displacement of the left kidney and ureter by a pseudocyst.\nPhotograph depicting extensive spontaneous abdominal wall hematoma and thigh hemorrhage in an older, previously unaffected man with an acquired factor VIII inhibitor.\nMagnetic resonance image of an extensive spontaneous abdominal wall hematoma and thigh hemorrhage in an older, previously unaffected man with an acquired factor VIII inhibitor.\nDouglass A Drelich, MD Director, Cardeza Foundation, Hemostasis and Thrombosis Center, Associate Director, Cardeza Special Coagulation Laboratory, Thomas Jefferson University Hospital; Assistant Professor of Medicine, Sidney Kimmel Medical College of Thomas Jefferson University\nDouglass A Drelich, MD is a member of the following medical societies: American Medical Association, American Society of Clinical Oncology, American Society of Hematology\nDisclosure: Received income in an amount equal to or greater than $250 from: Bayer, Octapharma, BPL, CSL Behring (Advisor Board Member).\nSrikanth Nagalla, MBBS, MS, FACP Associate Professor of Medicine, Division of Hematology and Oncology, UT Southwestern Medical Center\nSrikanth Nagalla, MBBS, MS, FACP is a member of the following medical societies: American Society of Hematology, Association of Specialty Professors\nDisclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Alexion; Alnylam.\nEmmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University\nEmmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences\nMary A Furlong, MD Associate Professor and Program/Residency Director, Department of Pathology, Georgetown University School of Medicine\nMary A Furlong, MD is a member of the following medical societies: United States and Canadian Academy of Pathology\nGary D Crouch, MD Associate Professor, Program Director of Pediatric Hematology-Oncology Fellowship, Department of Pediatrics, Uniformed Services University of the Health Sciences\nGary D Crouch, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Hematology\nRobert A Zaiden, MD Assistant Professor, Division of Hematology/Oncology, Department of Medicine, University of Florida at Jacksonville College of Medicine\nRobert A Zaiden, MD is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology\nDimitrios P Agaliotis, MD, PhD, FACP Consulting Staff, Department of Medicine, Baptist Health System\nDimitrios P Agaliotis, MD, PhD, FACP is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Hematology, and Florida Medical Association\nJeffrey L Arnold, MD, FACEP Chairman, Department of Emergency Medicine, Santa Clara Valley Medical Center\nJeffrey L Arnold, MD, FACEP is a member of the following medical societies: American Academy of Emergency Medicine and American College of Physicians\nEmmanuel C Besa, MD Professor, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University\nEmmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences\nMax J Coppes, MD, PhD, MBA President, BC Cancer Agency, Vancouver\nMax J Coppes, MD, PhD, MBA, is a member of the following medical societies: Alberta Medical Association, American College of Healthcare Executives, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research\nDisclosure: Astellas Pharma US Inc Honoraria Chair Endpoint Review Committee\nBrendan R Furlong, MD Clinical Chief, Department of Emergency Medicine, Georgetown University Hospital\nBrendan R Furlong, MD is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine\nPere Gascon, MD, PhD Professor and Director, Division of Medical Oncology, Institute of Hematology and Medical Oncology, IDIBAPS, University of Barcelona Faculty of Medicine, Spain\nPere Gascon, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, New York Academy of Medicine, New York Academy of Sciences, and Sigma Xi\nWilliam G Gossman, MD Associate Clinical Professor of Emergency Medicine, Creighton University School of Medicine; Consulting Staff, Department of Emergency Medicine, Creighton University Medical Center\nWilliam G Gossman, MD is a member of the following medical societies: American Academy of Emergency Medicine\nLawrence F Jardine, MD, FRCPC Associate Professor, Department of Pediatrics, Schulich School of Medicine and Dentistry, University of Western Ontario; Head, Section of Pediatric Hematology and Oncology, Children's Hospital of Western Ontario; Associate Scientist, Child Health Research Institute\nLawrence F Jardine, MD, FRCPC is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, Canadian Medical Protective Association, Children's Oncology Group, College of Physicians and Surgeons of Ontario, Hemophilia and Thrombosis Research Society, Ontario Medical Association, and Royal College of Physicians and Surgeons of Canada\nDisclosure: Baxter Honoraria Consulting; Bayer Honoraria Consulting; Novartis Honoraria Speaking and teaching\nElzbieta Klujszo, MD Head of Department of Dermatology, Wojewodzki Szpital Zespolony, Kielce\nAdonis Lorenzana, MD Consulting Staff, Department of Pediatric Oncology, St John Hospital and Medical Center\nAdonis Lorenzana, MD is a member of the following medical societies: American Academy of Pediatrics and American Society of Pediatric Hematology/Oncology\nRajalaxmi McKenna, MD, FACP Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems\nRajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis\nSaduman Ozturk, PA-C Physician Assistant, Bone Marrow Transplant Center, Florida Hospital Cancer Institute\nRonald A Sacher, MB, BCh, MD, FRCPC Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center\nRonald A Sacher, MB, BCh, MD, FRCPC is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, and Royal College of Physicians and Surgeons of Canada\nDisclosure: Glaxo Smith Kline Honoraria Speaking and teaching\nHadi Sawaf, MD Director, Pediatric Hematology Oncology, Van Elslander Cancer Center; Clinical Assistant Professor, Wayne State University School of Medicine\nHadi Sawaf, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Clinical Oncology, and American Society of Hematology\nRebecca J Schmidt, DO, FACP, FASN Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine\nRebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association\nDisclosure: Renal Ventures Ownership interest Other\nRobert A Schwartz, MD, MPH Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School\nRobert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, New York Academy of Medicine, and Sigma Xi\nKaren Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College\nKaren Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, and American Society of Hematology\nDisclosure: Novartis Honoraria Speaking and teaching; Novartis Consulting fee Speaking and teaching; Ariad Honoraria Speaking and teaching; Celgene Honoraria Speaking and teaching\nThe authors gratefully acknowledge the provision of several photographs used in this article by a dedicated colleague from Chicago, Margaret Telfer, MD. The authors would also like to acknowledge Professor K.N. Subramanian (Department of Molecular Genetics, University of Illinois Medical Center) for general discussions relating to some aspects of the gene structure and mutation of the FVIII gene."