The dramatic hemorrhages, the effect of the disease on historythrough its presence in Queen Victoria's descendants, and thedevastating role of therapeutic concentrates in the transmissionof the acquired immunodeficiency syndrome (AIDS) have made hemophiliaA the object of great medical, scientific, and public interest.The commonest hereditary coagulation disorder and a diseasewithout ethnic or geographic limitations, its incidence approaches20 per 100,000 male births1,2,3. John Conrad Otto emphasizedits inheritance as an X-linked disorder in his 1803 descriptionof the disease in a New Hampshire family: "males only are subjectto this strong affection . . . . . [Full Text of this Article]
The Role of Factor VIII in Blood Coagulation
The Structure and Function of Factor VIII
Molecular Genetics of Hemophilia A
Clinical Presentation
Factor VIII Replacement Therapy
Clinical Management
Genetic Counseling and Prenatal Diagnosis
The Future
Source Information
From the Holland Laboratory, American Red Cross Biomedical Services, 15601 Crabbs Branch Way, Rockville, MD 20855, where reprint requests should be addressed to Dr. Hoyer.
Lacroix-Desmazes, S., Navarrete, A.-M., Andre, S., Bayry, J., Kaveri, S. V., Dasgupta, S.
(2008). Dynamics of factor VIII interactions determine its immunologic fate in hemophilia A. Blood
112: 240-249
[Abstract][Full Text]
Shen, B. W., Spiegel, P. C., Chang, C.-H., Huh, J.-W., Lee, J.-S., Kim, J., Kim, Y.-H., Stoddard, B. L.
(2008). The tertiary structure and domain organization of coagulation factor VIII. Blood
111: 1240-1247
[Abstract][Full Text]
Ohmori, T., Mimuro, J., Takano, K., Madoiwa, S., Kashiwakura, Y., Ishiwata, A., Niimura, M., Mitomo, K., Tabata, T., Hasegawa, M., Ozawa, K., Sakata, Y.
(2006). Efficient expression of a transgene in platelets using simian immunodeficiency virus-based vector harboring glycoprotein Ib{alpha} promoter: in vivo model for platelet-targeting gene therapy. FASEB J.
20: 1522-1524
[Abstract][Full Text]
Mackman, N.
(2005). Tissue-Specific Hemostasis in Mice. Arterioscler. Thromb. Vasc. Bio.
25: 2273-2281
[Abstract][Full Text]
Kang, Y., Xie, L., Tran, D. T., Stein, C. S., Hickey, M., Davidson, B. L., McCray, P. B. Jr
(2005). Persistent expression of factor VIII in vivo following nonprimate lentiviral gene transfer. Blood
106: 1552-1558
[Abstract][Full Text]
Ghosh, N., Marotta, P. J., McAlister, V. C.
(2005). Correction of Factor XI Deficiency by Liver Transplantation. NEJM
352: 2357-2358
[Full Text]
Scott, D. W., Ananyeva, N. M.
(2004). Mutagenesis lowers factor VIII immunogenicity. Blood
104: 598-599
[Full Text]
Benndorf, G., Kim, D. M., Menneking, H., Klein, M.
(2004). Endovascular Management of a Mandibular Arteriovenous Malformation in a Patient with Severe Hemophilia A. Am. J. Neuroradiol.
25: 614-617
[Abstract][Full Text]
Burke, W.
(2003). Genomics as a Probe for Disease Biology. NEJM
349: 969-974
[Full Text]
Hockin, M. F., Jones, K. C., Everse, S. J., Mann, K. G.
(2002). A Model for the Stoichiometric Regulation of Blood Coagulation. J. Biol. Chem.
277: 18322-18333
[Abstract][Full Text]
van den Brink, E. N., Bril, W. S., Turenhout, E. A. M., Zuurveld, M., Bovenschen, N., Peters, M., Yee, T. T., Mertens, K., Lewis, D. A., Ortel, T. L., Lollar, P., Scandella, D., Voorberg, J.
(2002). Two classes of germline genes both derived from the VH1 family direct the formation of human antibodies that recognize distinct antigenic sites in the C2 domain of factor VIII. Blood
99: 2828-2834
[Abstract][Full Text]
Butenas, S., Brummel, K. E., Branda, R. F., Paradis, S. G., Mann, K. G.
(2002). Mechanism of factor VIIa-dependent coagulation in hemophilia blood. Blood
99: 923-930
[Abstract][Full Text]
Lin, Y., Chang, L., Solovey, A., Healey, J. F., Lollar, P., Hebbel, R. P.
(2002). Use of blood outgrowth endothelial cells for gene therapy for hemophilia A. Blood
99: 457-462
[Abstract][Full Text]
Mannucci, P. M.
(2002). Ham-Wasserman Lecture : Hemophilia and Related Bleeding Disorders: A Story of Dismay and Success. ASH Education Book
2002: 1-9
[Abstract][Full Text]
Aledort, L. M., Mariani, G., Kroner, B. L., Brackmann, H. H., Punch, J. D., Merion, R. M., Turcotte, J. G., Mannucci, P. M., Tuddenham, E. D.G.
(2001). Hemophilia. NEJM
345: 1066-1067
[Full Text]
Minhas, H L, Giangrande, P L F
(2001). Presentation of severe haemophilia--A role for accident and emergency doctors?. Emerg. Med. J.
18: 246-249
[Abstract][Full Text]
Mannucci, P. M., Tuddenham, E. G.D.
(2001). The Hemophilias -- From Royal Genes to Gene Therapy. NEJM
344: 1773-1779
[Full Text]
Rossi, G., Sarkar, J., Scandella, D.
(2001). Long-term induction of immune tolerance after blockade of CD40-CD40L interaction in a mouse model of hemophilia A. Blood
97: 2750-2757
[Abstract][Full Text]
van den Brink, E. N., Turenhout, E. A. M., Bovenschen, N., Heijnen, B. G. A. D. H., Mertens, K., Peters, M., Voorberg, J.
(2001). Multiple VH genes are used to assemble human antibodies directed toward the A3-C1 domains of factor VIII. Blood
97: 966-972
[Abstract][Full Text]
Gallo-Penn, A. M., Shirley, P. S., Andrews, J. L., Tinlin, S., Webster, S., Cameron, C., Hough, C., Notley, C., Lillicrap, D., Kaleko, M., Connelly, S.
(2001). Systemic delivery of an adenoviral vector encoding canine factor VIII results in short-term phenotypic correction, inhibitor development, and biphasic liver toxicity in hemophilia A dogs. Blood
97: 107-113
[Abstract][Full Text]
Weitz, J. I., Hirsh, J.
(2001). New Anticoagulant Drugs. Chest
119: 95S-107S
[Full Text]
van den Brink, E. N., Turenhout, E. A. M., Bank, C. M. C., Fijnvandraat, K., Peters, M., Voorberg, J.
(2000). Molecular analysis of human anti-factor VIII antibodies by V gene phage display identifies a new epitope in the acidic region following the A2 domain. Blood
96: 540-545
[Abstract][Full Text]
Al-Jarallah, A., Al-Rifai, M. T., Riela, A. R., Roach, E. S.
(2000). Nontraumatic Brain Hemorrhage in Children: Etiology and Presentation. J Child Neurol
15: 284-289
[Abstract]
Qian, J., Collins, M., Sharpe, A. H., Hoyer, L. W.
(2000). Prevention and treatment of factor VIII inhibitors in murine hemophilia A. Blood
95: 1324-1329
[Abstract][Full Text]
Balague, C., Zhou, J., Dai, Y., Alemany, R., Josephs, S. F., Andreason, G., Hariharan, M., Sethi, E., Prokopenko, E., Jan, H.-y., Lou, Y.-C., Hubert-Leslie, D., Ruiz, L., Zhang, W.-W.
(2000). Sustained high-level expression of full-length human factor VIII and restoration of clotting activity in hemophilic mice using a minimal adenovirus vector. Blood
95: 820-828
[Abstract][Full Text]
van den Brink, E. N., Turenhout, E. A. M., Davies, J., Bovenschen, N., Fijnvandraat, K., Ouwehand, W. H., Peters, M., Voorberg, J.
(2000). Human antibodies with specificity for the C2 domain of factor VIII are derived from VH1 germline genes. Blood
95: 558-563
[Abstract][Full Text]
Hedner, U., Ginsburg, D., Lusher, J. M., High, K. A.
(2000). Congenital Hemorrhagic Disorders: New Insights into the Pathophysiology and Treatment of Hemophilia. ASH Education Book
2000: 241-265
[Abstract][Full Text]
Butenas, S., van't Veer, C., Mann, K. G.
(1999). "Normal" Thrombin Generation. Blood
94: 2169-2178
[Abstract][Full Text]
Connelly, S., Andrews, J. L., Gallo, A. M., Kayda, D. B., Qian, J., Hoyer, L., Kadan, M. J., Gorziglia, M. I., Trapnell, B. C., McClelland, A., Kaleko, M.
(1998). Sustained Phenotypic Correction of Murine Hemophilia A by In Vivo Gene Therapy. Blood
91: 3273-3281
[Abstract][Full Text]
Fijnvandraat, K., Celie, P. H.N., Turenhout, E. A.M., ten Cate, J. W., van Mourik, J. A., Mertens, K., Peters, M., Voorberg, J.
(1998). A Human Alloantibody Interferes With Binding of Factor IXa to the Factor VIII Light Chain. Blood
91: 2347-2352
[Abstract][Full Text]
Ewenstein, B. M., Van Cott, E.
(1998). Case 6-1998- A Six-Year-Old Boy with Both Pain and a Bloody Effusion in the Right Hip. NEJM
338: 532-539
[Full Text]
Carmeliet, P., Collen, D.
(1997). Molecular analysis of blood vessel formation and disease. Am. J. Physiol. Heart Circ. Physiol.
273: H2091-H2104
[Abstract][Full Text]
van `t Veer, C., Golden, N. J., Kalafatis, M., Simioni, P., Bertina, R. M., Mann, K. G.
(1997). An In Vitro Analysis of the Combination of Hemophilia A and Factor VLEIDEN. Blood
90: 3067-3072
[Abstract][Full Text]
Fijnvandraat, K., Turenhout, E. A.M., van den Brink, E. N., ten Cate, J. W., van Mourik, J. A., Peters, M., Voorberg, J.
(1997). The Missense Mutation Arg593 right-arrow Cys Is Related to Antibody Formation in a Patient With Mild Hemophilia A. Blood
89: 4371-4377
[Abstract][Full Text]
Pierce, G. F., Rosner, F.
(1994). Hemophilia A. NEJM
330: 1617-1617
[Full Text]