title: New treatments in hemophilia: insights for the clinician.
abstract: Hemophilia has evolved from an often fatal hereditary bleeding disorder to a disorder for which safe and effective treatment is available. However, there are several challenges remaining in the treatment of hemophilia. Prophylaxis to prevent bleeding is costly and requires frequent intravenous injections, which are cumbersome for patients. Venous access is often difficult to achieve, especially in small children where central venous lines may need to be implanted. Development of inhibitory antibodies makes treatment of acute bleeds difficult and prophylaxis in patients with inhibitors must also be better addressed. In order to improve treatment, new products are being developed, some of which are already in clinical trials. There are several approaches to prolonging half-lives such as PEGylation, Fc fusion and albumin fusion. Increased activity has been demonstrated in preclinical trials for factor IX and in a human trial with factor VII where the activity of the molecules has been increased by manipulation of the molecular composition. Additional approaches, including blockage of inhibitors of clotting, are also under investigation. Factor VIII and factor IX gene therapy have become a tangible possibility since phase I data recently have been published. Results are promising and there is hope that in the near future substantial progress will be made, perhaps making hemophilia the first genetic condition to be cured.
authors.affiliation: Malmö Centre for Thrombosis and Haemostasis, Skåne University Hospital, SE-205 02 Malmö, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Knobe
authors.forename: Erik
authors.initials: E
authors.lastname: Berntorp
keywords: coagulation; factor IX; factor VIII; hemophilia; treatment
references.citation: J Thromb Haemost. 2011 Jul;9(7):1368-74
references.pmid: 21575130
references.citation: Drug Metab Dispos. 2007 Jan;35(1):9-16
references.pmid: 17020954
references.citation: Haemophilia. 2005 Sep;11(5):438-43
references.pmid: 16128885
references.citation: J Clin Invest. 1997 Aug 15;100(4):886-92
references.pmid: 9259588
references.citation: Haemophilia. 2007 Dec;13 Suppl 5:65-8
references.pmid: 18078400
references.citation: Haemophilia. 2004 Nov;10(6):689-97
references.pmid: 15569163
references.citation: Lancet. 1971 Feb 27;1(7696):450
references.pmid: 4100418
references.citation: Blood. 2006 Jan 1;107(1):46-51
references.pmid: 16166584
references.citation: Acta Paediatr. 1992 Nov;81(11):918-20
references.pmid: 1467614
references.citation: Blood. 2012 Jan 19;119(3):666-72
references.pmid: 22110246
references.citation: N Engl J Med. 2009 Jan 29;360(5):447-58
references.pmid: 19179314
references.citation: Br J Haematol. 2001 Mar;112(3):561-5
references.pmid: 11260054
references.citation: Haemophilia. 2004 Oct;10 Suppl 4:94-6
references.pmid: 15479379
references.citation: Thromb Haemost. 2001 Feb;85(2):218-20
references.pmid: 11246535
references.citation: Haemophilia. 2006 Jul;12 Suppl 3:159-68
references.pmid: 16684012
references.citation: J Thromb Haemost. 2009 Feb;7(2):299-305
references.pmid: 19138379
references.citation: Acta Med Scand Suppl. 1984;684:1-72
references.pmid: 6611018
references.citation: Ann Hematol. 1998 Oct;77(4):171-4
references.pmid: 9829849
references.citation: J Intern Med. 1992 Jul;232(1):25-32
references.pmid: 1640190
references.citation: Arterioscler Thromb Vasc Biol. 2007 Mar;27(3):683-9
references.pmid: 17204663
references.citation: J Thromb Haemost. 2007 May;5(5):901-6
references.pmid: 17459005
references.citation: Br J Haematol. 2005 Aug;130(3):422-7
references.pmid: 16042693
references.citation: Blood. 2006 Dec 1;108(12):3668-73
references.pmid: 16888098
references.citation: Haemophilia. 2002 Mar;8 Suppl 2:34-7
references.pmid: 11966851
references.citation: Haemophilia. 1998 Mar;4(2):83-8
references.pmid: 9873843
references.citation: Thromb Haemost. 2008 Apr;99(4):659-67
references.pmid: 18392323
references.citation: Haemophilia. 2005 Jul;11(4):335-9
references.pmid: 16011584
references.citation: Haemophilia. 1999 May;5(3):145-54
references.pmid: 10444280
references.citation: Blood. 2000 Jul 15;96(2):437-42
references.pmid: 10887103
references.citation: Semin Hematol. 2006 Apr;43(2 Suppl 4):S3-7
references.pmid: 16690373
references.citation: J Pharm Sci. 2010 Jun;99(6):2557-75
references.pmid: 20049941
references.citation: Blood. 2007 Jun 1;109(11):4693-7
references.pmid: 17218379
references.citation: Blood. 2011 Sep 8;118(10):2695-701
references.pmid: 21555744
references.citation: Acta Haematol. 1969;41(4):206-14
references.pmid: 4979341
references.citation: Hematol Oncol Clin North Am. 2010 Feb;24(1):181-98
references.pmid: 20113902
references.citation: Haemophilia. 1998 Jul;4(4):498-501
references.pmid: 9873781
references.citation: Blood. 2008 Jan 15;111(2):672-9
references.pmid: 17978172
references.citation: J Clin Immunol. 2010 Nov;30(6):777-89
references.pmid: 20886282
references.citation: J Thromb Haemost. 2009 Sep;7(9):1517-22
references.pmid: 19566792
references.citation: Thromb Res. 2011 Jan;127 Suppl 2:S22-5
references.pmid: 21193110
references.citation: Acta Haematol. 1971;45(2):120-7
references.pmid: 4996566
references.citation: Proc Natl Acad Sci U S A. 2010 Apr 13;107(15):7101-6
references.pmid: 20351275
references.citation: Haemophilia. 1998 Jul;4(4):413-7
references.pmid: 9873763
references.citation: Eur J Haematol. 1993 Oct;51(4):247-52
references.pmid: 8243614
references.citation: Thromb Haemost. 2001 Mar;85(3):560
references.pmid: 11307831
references.citation: J Thromb Haemost. 2010 Jun;8(6):1256-65
references.pmid: 20345722
references.citation: J Biol Chem. 1998 May 15;273(20):12089-94
references.pmid: 9575152
references.citation: J Thromb Haemost. 2006 Jun;4(6):1228-36
references.pmid: 16706965
references.citation: J Pediatr. 1996 Sep;129(3):424-31
references.pmid: 8804333
references.citation: Haemophilia. 2010 Nov;16(6):910-8
references.pmid: 20491957
references.citation: Blood. 2010 Mar 11;115(10):2057-64
references.pmid: 20056791
references.citation: Blood Rev. 2009 Nov;23(6):267-74
references.pmid: 19775786
references.citation: Blood. 2007 Jun 1;109(11):4648-54
references.pmid: 17289808
references.citation: J Intern Med. 1994 Oct;236(4):391-9
references.pmid: 7931042
references.citation: Haemophilia. 2005 Mar;11(2):92-9
references.pmid: 15810909
references.citation: Nat Biotechnol. 1997 Oct;15(10):971-5
references.pmid: 9335047
references.citation: Am J Pediatr Hematol Oncol. 1991 Fall;13(3):280-7
references.pmid: 1793153
references.citation: Blood. 2009 Jul 23;114(4):871-80
references.pmid: 19411636
references.citation: N Engl J Med. 2011 Dec 22;365(25):2357-65
references.pmid: 22149959
references.citation: Haemophilia. 2006 Jul;12(4):363-71
references.pmid: 16834735
references.citation: Nature. 2007 May 3;447(7140):87-91
references.pmid: 17450125
references.citation: Blood. 2007 Jan 15;109(2):610-2
references.pmid: 16985172
references.citation: Haemophilia. 2006 Jan;12(1):75-81
references.pmid: 16409179
references.citation: Br J Haematol. 2006 Mar;132(6):798-800; author reply 800-1
references.pmid: 16487187
references.citation: J Thromb Haemost. 2011 Nov;9(11):2235-42
references.pmid: 21920013
references.citation: Haemophilia. 2007 Jan;13(1):38-45
references.pmid: 17212723
references.citation: N Engl J Med. 2002 Sep 26;347(13):975-82
references.pmid: 12324553
references.citation: Thromb Haemost. 2008 Sep;100(3):429-34
references.pmid: 18766258
references.citation: Thromb Haemost. 2006 Jan;95(1):68-76
references.pmid: 16543964
references.citation: Haemophilia. 2008 Jan;14 Suppl 1:1-4
references.pmid: 18173688
references.citation: Drugs. 2003;63(7):701-30
references.pmid: 12656650
references.citation: J Clin Invest. 2000 Oct;106(8):929-34
references.pmid: 11032851
references.citation: Genet Anal. 1999 Nov;15(3-5):155-60
references.pmid: 10596756
references.citation: Blood. 2010 Jul 15;116(2):270-9
references.pmid: 20194895
references.citation: J Clin Pharmacol. 2007 Apr;47(4):430-44
references.pmid: 17389552
references.citation: Haemophilia. 2002 Mar;8(2):76-82
references.pmid: 11952841
references.citation: Br J Haematol. 1999 Jun;105(4):1109-13
references.pmid: 10554828
references.citation: Br J Haematol. 2007 Apr;137(2):158-65
references.pmid: 17391496
references.citation: Haemophilia. 2002 Mar;8 Suppl 2:23-9
references.pmid: 11966849
references.citation: Blood. 2011 Aug 25;118(8):2333-41
references.pmid: 21700771