Factor VIII and von Willebrand factor interaction: Biological, clinical and therapeutic importance

Haemophilia

Volumn 16, Issue 1, 2010, Pages 3-13

  Terraube, V ^a   O'Donnell, J S ^b   Jenkins, P V ^b  

^a TRINITY COLLEGE DUBLIN   (Ireland)

^b ST JAMES S HOSPITAL   (Ireland)

Author keywords

Factor VIII; Haemophilia A; Von Willebrand factor; Von Willebrand's disease

Indexed keywords

BLOOD CLOTTING FACTOR 8; CELL RECEPTOR; FIBRIN; PROTEINASE; RECOMBINANT BLOOD CLOTTING FACTOR 8; THROMBIN; VON WILLEBRAND FACTOR; VON WILLEBRAND FACTOR CLEAVING PROTEINASE;

BINDING AFFINITY; BLOOD CLOTTING; BLOOD VESSEL INJURY; CELL BASED GENE THERAPY; CELL INTERACTION; CELL TYPE; GENE MUTATION; HEMOPHILIA A; HEMOSTASIS; HUMAN; IMMUNE RESPONSE; MUTATIONAL ANALYSIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN BLOOD LEVEL; PROTEIN FUNCTION; PROTEIN INDUCTION; PROTEIN PROTEIN INTERACTION; PROTEIN STABILITY; REVIEW; VON WILLEBRAND DISEASE;

BLOOD COAGULATION; FACTOR VIII; GENE THERAPY; HEMOPHILIA A; HEMOSTASIS; HUMANS; VON WILLEBRAND DISEASES; VON WILLEBRAND FACTOR;

EID: 73949137584     PISSN: 13518216     EISSN: 13652516     Source Type: Journal    
DOI: 10.1111/j.1365-2516.2009.02005.x     Document Type: Review

References (110)

1. Zimmerman TS, Edgington TS. Factor VIII coagulant activity and factor VIII-like antigen: independent molecular entities. J Exp Med 1973, 138:1015-20.
2. Sakariassen KS, Bolhuis PA, Sixma JJ. Human blood platelet adhesion to artery subendothelium is mediated by factor VIII-Von Willebrand factor bound to the subendothelium. Nature 1979, 279:636-8.
3. Fay PJ. Activation of factor VIII and mechanisms of cofactor action. Blood Rev 2004, 18:1-15.
4. Wion KL, Kelly D, Summerfield JA, Tuddenham EG, Lawn RM. Distribution of factor VIII mRNA and antigen in human liver and other tissues. Nature 1985, 317:726-9.
5. Stel HV, van der Kwast TH, Veerman EC. Detection of factor VIII/coagulant antigen in human liver tissue. Nature 1983, 303:530-2.
6. van der Kwast TH, Stel HV, Cristen E, Bertina RM, Veerman EC. Localization of factor VIII-procoagulant antigen: an immunohistological survey of the human body using monoclonal antibodies. Blood 1986, 67:222-7.
7. Hollestelle MJ, Thinnes T, Crain K. Tissue distribution of factor VIII gene expression in vivo - a closer look. Thromb Haemost 2001, 86:855-61.
8. Hollestelle MJ, Poyck PP, Hollestelle JM, Marsman HA, Mourik JA, Gulik TM. Extra-hepatic factor VIII expression in porcine fulminant hepatic failure. J Thromb Haemost 2005, 3:2274-80.
9. Jacquemin M, Neyrinck A, Hermanns MI. FVIII production by human lung microvascular endothelial cells. Blood 2006, 108:515-7.
10. Follenzi A, Benten D, Novikoff P, Faulkner L, Raut S, Gupta S. Transplanted endothelial cells repopulate the liver endothelium and correct the phenotype of hemophilia A mice. J Clin Invest 2008, 118:935-45.
11. Wagner DD. Cell biology of von Willebrand factor. Annu Rev Cell Biol 1990, 6:217-46.
12. Sporn LA, Chavin SI, Marder VJ, Wagner DD. Biosynthesis of von Willebrand protein by human megakaryocytes. J Clin Invest 1985, 76:1102-6.
13. Wu QY, Drouet L, Carrier JL. Differential distribution of von Willebrand factor in endothelial cells. Comparison between normal pigs and pigs with von Willebrand disease. Arteriosclerosis 1987, 7:47-54.
14. Yamamoto K, de Waard V, Fearns C, Loskutoff DJ. Tissue distribution and regulation of murine von Willebrand factor gene expression in vivo. Blood 1998, 92:2791-801.
15. Rosenberg JB, Foster PA, Kaufman RJ. Intracellular trafficking of factor VIII to von Willebrand factor storage granules. J Clin Invest 1998, 101:613-24.
16. Wilcox DA, Shi Q, Nurden P. Induction of megakaryocytes to synthesize and store a releasable pool of human factor VIII. J Thromb Haemost 2003, 1:2477-89.
17. Shi Q, Wilcox DA, Fahs SA, Kroner PA, Montgomery RR. Expression of human factor VIII under control of the platelet-specific alphaIIb promoter in megakaryocytic cell line as well as storage together with VWF. Mol Genet Metab 2003, 79:25-33.
18. Lamont PA, Ragni MV. Lack of desmopressin (DDAVP) response in men with hemophilia A following liver transplantation. J Thromb Haemost 2005, 3:2259-63.
19. Haberichter SL, Shi Q, Montgomery RR. Regulated release of VWF and FVIII and the biologic implications. Pediatr Blood Cancer 2006, 46:547-53.
20. Ganz PR, Atkins JS, Palmer DS, Dudani AK, Hashemi S, Luison F. Definition of the affinity of binding between human von Willebrand factor and coagulation factor VIII. Biochem Biophys Res Commun 1991, 180:231-7.
21. Vlot AJ, Koppelman SJ, van den Berg MH, Bouma BN, Sixma JJ. The affinity and stoichiometry of binding of human factor VIII to von Willebrand factor. Blood 1995, 85:3150-7.
22. Saenko EL, Loster K, Josic D, Sarafanov AG. Effect of von Willebrand Factor and its proteolytic fragments on kinetics of interaction between the light and heavy chains of human factor VIII. Thromb Res 1999, 96:343-54.
23. Hamer RJ, Koedam JA, Beeser-Visser NH, Bertina RM, Van Mourik JA, Sixma JJ. Factor VIII binds to von Willebrand factor via its Mr-80,000 light chain. Eur J Biochem 1987, 166:37-43.
24. Lollar P, Hill-Eubanks DC, Parker CG. Association of the factor VIII light chain with von Willebrand factor. J Biol Chem 1988, 263:10451-5.
25. Leyte A, Verbeet MP, Brodniewicz-Proba T, Van Mourik JA, Mertens K. The interaction between human blood-coagulation factor VIII and von Willebrand factor. Characterization of a high-affinity binding site on factor VIII. Biochem J 1989, 257:679-83.
26. Foster PA, Fulcher CA, Houghten RA, Zimmerman TS. An immunogenic region within residues Val1670-Glu1684 of the factor VIII light chain induces antibodies which inhibit binding of factor VIII to von Willebrand factor. J Biol Chem 1988, 263:5230-4.
27. Saenko EL, Scandella D. The acidic region of the factor VIII light chain and the C2 domain together form the high affinity binding site for von willebrand factor. J Biol Chem 1997, 272:18007-14.
28. Leyte A, van Schijndel HB, Niehrs C. Sulfation of Tyr1680 of human blood coagulation factor VIII is essential for the interaction of factor VIII with von Willebrand factor. J Biol Chem 1991, 266:740-6.
29. Ngo JC, Huang M, Roth DA, Furie BC, Furie B. Crystal structure of human factor VIII: implications for the formation of the factor IXa-factor VIIIa complex. Structure 2008, 16:597-606.
30. Shen BW, Spiegel PC, Chang CH. The tertiary structure and domain organization of coagulation factor VIII. Blood 2008, 111:1240-7.
31. Gilbert GE, Kaufman RJ, Arena AA, Miao H, Pipe SW. Four hydrophobic amino acids of the factor VIII C2 domain are constituents of both the membrane-binding and von Willebrand factor-binding motifs. J Biol Chem 2002, 277:6374-81.
32. Jacquemin M, Lavend'homme R, Benhida A. A novel cause of mild/moderate hemophilia A: mutations scattered in the factor VIII C1 domain reduce factor VIII binding to von Willebrand factor. Blood 2000, 96:958-65.
33. Titani K, Kumar S, Takio K. Amino acid sequence of human von Willebrand factor. Biochemistry 1986, 25:3171-84.
34. Matsui T, Titani K, Mizuochi T. Structures of the asparagine-linked oligosaccharide chains of human von Willebrand factor. Occurrence of blood group A, B, and H(O) structures. J Biol Chem 1992, 267:8723-31.
35. Foster PA, Fulcher CA, Marti T, Titani K, Zimmerman TS. A major factor VIII binding domain resides within the amino-terminal 272 amino acid residues of von Willebrand factor. J Biol Chem 1987, 262:8443-6.
36. Jorieux S, Magallon T, Mazurier C. Evidence that NH2-terminal but not COOH-terminal moiety of plasma von Willebrand factor binds to factor VIII. Thromb Res 1987, 48:205-10.
37. Takahashi Y, Kalafatis M, Girma JP, Sewerin K, Andersson LO, Meyer D. Localization of a factor VIII binding domain on a 34 kilodalton fragment of the N-terminal portion of von Willebrand factor. Blood 1987, 70:1679-82.
38. Pietu G, Ribba AS, Meulien P, Meyer D. Localization within the 106 N-terminal amino acids of von Willebrand factor (vWF) of the epitope corresponding to a monoclonal antibody which inhibits vWF binding to factor VIII. Biochem Biophys Res Commun 1989, 163:618-26.
39. Bahou WF, Ginsburg D, Sikkink R, Litwiller R, Fass DN. A monoclonal antibody to von Willebrand factor (vWF) inhibits factor VIII binding. Localization of its antigenic determinant to a nonadecapeptide at the amino terminus of the mature vWF polypeptide. J Clin Invest 1989, 84:56-61.
40. Wise RJ, Dorner AJ, Krane M, Pittman DD, Kaufman RJ. The role of von Willebrand factor multimers and propeptide cleavage in binding and stabilization of factor VIII. J Biol Chem 1991, 266:21948-55.
41. Bendetowicz AV, Morris JA, Wise RJ, Gilbert GE, Kaufman RJ. Binding of factor VIII to von willebrand factor is enabled by cleavage of the von Willebrand factor propeptide and enhanced by formation of disulfide-linked multimers. Blood 1998, 92:529-38.
42. Cacheris PM, Nichols WC, Ginsburg D. Molecular characterization of a unique von Willebrand disease variant. A novel mutation affecting von Willebrand factor/factor VIII interaction. J Biol Chem 1991, 266:13499-502.
43. Kroner PA, Friedman KD, Fahs SA, Scott JP, Montgomery RR. Abnormal binding of factor VIII is linked with the substitution of glutamine for arginine 91 in von Willebrand factor in a variant form of von Willebrand disease. J Biol Chem 1991, 266:19146-9.
44. Jorieux S, Tuley EA, Gaucher C, Mazurier C, Sadler JE. The mutation Arg (53) - Trp causes von Willebrand disease Normandy by abolishing binding to factor VIII. Studies with recombinant von Willebrand factor. Blood 1992, 79:563-7.
45. Lavergne JM, Piao Y, Ribba AS. Functional analysis of the Arg91Gln substitution in the factor VIII binding domain of von Willebrand factor demonstrates variable phenotypic expression. Thromb Haemost 1993, 70:691-6.
46. Mazurier C, Gaucher C, Jorieux S, Goudemand M. Biological effect of desmopressin in eight patients with type 2N ('Normandy') von Willebrand disease. Collaborative Group. Br J Haematol 1994, 88:849-54.
47. Tuley EA, Gaucher C, Jorieux S, Worrall NK, Sadler JE, Mazurier C. Expression of von Willebrand factor 'Normandy': an autosomal mutation that mimics hemophilia A. Proc Natl Acad Sci USA 1991, 88:6377-81.
48. Casonato A, Sartorello F, Cattini MG. An Arg760Cys mutation in the consensus sequence of the von Willebrand factor propeptide cleavage site is responsible for a new von Willebrand disease variant. Blood 2003, 101:151-6.
49. Jorieux S, Gaucher C, Goudemand J, Mazurier C. A novel mutation in the D3 domain of von Willebrand factor markedly decreases its ability to bind factor VIII and affects its multimerization. Blood 1998, 92:4663-70.
50. Allen S, Abuzenadah AM, Blagg JL. Two novel type 2N von Willebrand disease-causing mutations that result in defective factor VIII binding, multimerization, and secretion of von Willebrand factor. Blood 2000, 95:2000-7.
51. Schneppenheim R, Lenk H, Obser T. Recombinant expression of mutations causing von Willebrand disease type Normandy: characterization of a combined defect of factor VIII binding and multimerization. Thromb Haemost 2004, 92:36-41.
52. Borchiellini A, Fijnvandraat K, ten Cate JW. Quantitative analysis of von Willebrand factor propeptide release in vivo: effect of experimental endotoxemia and administration of 1-deamino-8-d-arginine vasopressin in humans. Blood 1996, 88:2951-8.
53. Bendetowicz AV, Wise RJ, Gilbert GE. Collagen-bound von Willebrand factor has reduced affinity for factor VIII. J Biol Chem 1999, 274:12300-7.
54. Jenkins PV, O'Donnell JS. ABO blood group determines plasma von Willebrand factor levels: a biologic function after all? Transfusion 2006, 46:1836-44.
55. Preston AE, Barr A. The plasma concentration of factor VIII in the normal population. II. The effects of age, sex and blood group. Br J Haematol 1964, 10:238-45.
56. Mohanty D, Ghosh K, Marwaha N, Kaur S, Chauhan AP, Das KC. Major blood group antigens - a determinant of factor VIII levels in blood? Thromb Haemost 1984, 51:414.
57. Gill JC, Endres-Brooks J, Bauer PJ, Marks WJ, Montgomery RR. The effect of ABO blood group on the diagnosis of von Willebrand disease. Blood 1987, 69:1691-5.
58. O'Donnell J, Boulton FE, Manning RA, Laffan MA. Amount of H antigen expressed on circulating von Willebrand factor is modified by ABO blood group genotype and is a major determinant of plasma von Willebrand factor antigen levels. Arterioscler Thromb Vasc Biol 2002, 22:335-41.
59. Orstavik KH, Magnus P, Reisner H, Berg K, Graham JB, Nance W. Factor VIII and factor IX in a twin population. Evidence for a major effect of ABO locus on factor VIII level. Am J Hum Genet 1985, 37:89-101.
60. Morelli VM, de Visser MC, van Tilburg NH. ABO blood group genotypes, plasma von Willebrand factor levels and loading of von Willebrand factor with A and B antigens. Thromb Haemost 2007, 97:534-41.
61. Eikenboom JC, Castaman G, Kamphuisen PW, Rosendaal FR, Bertina RM. The factor VIII/von Willebrand factor ratio discriminates between reduced synthesis and increased clearance of von Willebrand factor. Thromb Haemost 2002, 87:252-7.
62. Morange PE, Tregouet DA, Frere C. Biological and genetic factors influencing plasma factor VIII levels in a healthy family population: results from the Stanislas cohort. Br J Haematol 2005, 128:91-9.
63. Balleisen L, Bailey J, Epping PH, Schulte H, van de Loo J. Epidemiological study on factor VII, factor VIII and fibrinogen in an industrial population: I. Baseline data on the relation to age, gender, body-weight, smoking, alcohol, pill-using, and menopause. Thromb Haemost 1985, 54:475-9.
64. Conlan MG, Folsom AR, Finch A. Associations of factor VIII and von Willebrand factor with age, race, sex, and risk factors for atherosclerosis. The Atherosclerosis Risk in Communities (ARIC) Study. Thromb Haemost 1993, 70:380-5.
65. Lima AM, Azevedo ES. Factor VIII:C, ABO blood groups, and black admixture in a Brazilian sample. Hum Biol 1991, 63:77-83.
66. Miller CH, Haff E, Platt SJ. Measurement of von Willebrand factor activity: relative effects of ABO blood type and race. J Thromb Haemost 2003, 1:2191-7.
67. Kadir RA, Economides DL, Sabin CA, Owens D, Lee CA. Variations in coagulation factors in women: effects of age, ethnicity, menstrual cycle and combined oral contraceptive. Thromb Haemost 1999, 82:1456-61.
68. Kamphuisen PW, Houwing-Duistermaat JJ, van Houwelingen HC, Eikenboom JC, Bertina RM, Rosendaal FR. Familial clustering of factor VIII and von Willebrand factor levels. Thromb Haemost 1998, 79:323-7.
69. Tuddenham EG, Lane RS, Rotblat F. Response to infusions of polyelectrolyte fractionated human factor VIII concentrate in human haemophilia A and von Willebrand's disease. Br J Haematol 1982, 52:259-67.
70. Kaufman RJ, Dorner AJ, Fass DN. von Willebrand factor elevates plasma factor VIII without induction of factor VIII messenger RNA in the liver. Blood 1999, 93:193-7.
71. Borel-Derlon A, Federici AB, Roussel-Robert V. Treatment of severe von Willebrand disease with a high-purity von Willebrand factor concentrate (Wilfactin): a prospective study of 50 patients. J Thromb Haemost 2007, 5:1115-24.
72. Kaufman RJ, Wasley LC, Davies MV, Wise RJ, Israel DI, Dorner AJ. Effect of von Willebrand factor coexpression on the synthesis and secretion of factor VIII in Chinese hamster ovary cells. Mol Cell Biol 1989, 9:1233-42.
73. Fay PJ. Reconstitution of human factor VIII from isolated subunits. Arch Biochem Biophys 1988, 262:525-31.
74. Koedam JA, Meijers JC, Sixma JJ, Bouma BN. Inactivation of human factor VIII by activated protein C. Cofactor activity of protein S and protective effect of von Willebrand factor. J Clin Invest 1988, 82:1236-43.
75. Fay PJ, Coumans JV, Walker FJ. von Willebrand factor mediates protection of factor VIII from activated protein C-catalyzed inactivation. J Biol Chem 1991, 266:2172-7.
76. Koppelman SJ, van Hoeij M, Vink T. Requirements of von Willebrand factor to protect factor VIII from inactivation by activated protein C. Blood 1996, 87:2292-300.
77. Koedam JA, Hamer RJ, Beeser-Visser NH, Bouma BN, Sixma JJ. The effect of von Willebrand factor on activation of factor VIII by factor Xa. Eur J Biochem 1990, 189:229-34.
78. Nesheim M, Pittman DD, Giles AR. The effect of plasma von Willebrand factor on the binding of human factor VIII to thrombin-activated human platelets. J Biol Chem 1991, 266:17815-20.
79. Saenko EL, Scandella D. A mechanism for inhibition of factor VIII binding to phospholipid by von Willebrand factor. J Biol Chem 1995, 270:13826-33.
80. Lenting PJ, van de Loo JW, Donath MJ, van Mourik JA, Mertens K. The sequence Glu1811-Lys1818 of human blood coagulation factor VIII comprises a binding site for activated factor IX. J Biol Chem 1996, 271:1935-40.
81. Nogami K, Shima M, Nishiya K. A novel mechanism of factor VIII protection by von Willebrand factor from activated protein C-catalyzed inactivation. Blood 2002, 99:3993-8.
82. Lenting PJ, Christophe OD, Gueguen P. The disappearing act of factor VIII. Haemophilia 2008, [Online]
83. Strickland DK, Medved L. Low-density lipoprotein receptor-related protein (LRP)-mediated clearance of activated blood coagulation co-factors and proteases: clearance mechanism or regulation? J Thromb Haemost 2006, 4:1484-6.
84. Lenting PJ, Neels JG, van den Berg BM. The light chain of factor VIII comprises a binding site for low density lipoprotein receptor-related protein. J Biol Chem 1999, 274:23734-9.
85. Sarafanov AG, Makogonenko EM, Pechik IV. Identification of coagulation factor VIII A2 domain residues forming the binding epitope for low-density lipoprotein receptor-related protein. Biochemistry 2006, 45:1829-40.
86. Bovenschen N, van Stempvoort G, Voorberg J, Mertens K, Meijer AB. Proteolytic cleavage of factor VIII heavy chain is required to expose the binding-site for low-density lipoprotein receptor-related protein within the A2 domain. J Thromb Haemost 2006, 4:1487-93.
87. Bovenschen N, Herz J, Grimbergen JM. Elevated plasma factor VIII in a mouse model of low-density lipoprotein receptor-related protein deficiency. Blood 2003, 101:3933-9.
88. Lenting PJ, Vans CJ, Denis CV. Clearance mechanisms of von Willebrand factor and factor VIII. J Thromb Haemost 2007, 5:1353-60.
89. van Schooten CJ, Shahbazi S, Groot E. Macrophages contribute to the cellular uptake of von Willebrand factor and factor VIII in vivo. Blood 2008, 112:1704-12.
90. Grewal PK, Uchiyama S, Ditto D. The Ashwell receptor mitigates the lethal coagulopathy of sepsis. Nat Med 2008, 14:648-55.
91. Millar CM, Riddell AF, Brown SA. Survival of von Willebrand factor released following DDAVP in a type 1 von Willebrand disease cohort: influence of glycosylation, proteolysis and gene mutations. Thromb Haemost 2008, 99:916-24.
92. Sadler JE. Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura. Blood 2008, 112:11-8.
93. Cao W, Krishnaswamy S, Camire RM, Lenting PJ, Zheng XL. Factor VIII accelerates proteolytic cleavage of von Willebrand factor by ADAMTS13. Proc Natl Acad Sci USA 2008, 105:7416-21.
94. Ettingshausen CE, Kreuz W. Recombinant vs. plasma-derived products, especially those with intact VWF, regarding inhibitor development. Haemophilia 2006, 12(Suppl. 6):102-6.
95. Gringeri A, Musso R, Mazzucconi MG. Immune tolerance induction with a high purity von Willebrand factor/VIII complex concentrate in haemophilia A patients with inhibitors at high risk of a poor response. Haemophilia 2007, 13:373-9.
96. Goudemand J, Rothschild C, Demiguel V. Influence of the type of factor VIII concentrate on the incidence of factor VIII inhibitors in previously untreated patients with severe hemophilia A. Blood 2006, 107:46-51.
97. Tagariello G, Zanotto D, Radossi P, Sartori R, Belvini D, Salviato R. In vitro reactivity of factor VIII inhibitors with von Willebrand factor in different commercial factor VIII concentrates. Am J Hematol 2007, 82:460-2.
98. Inoue T, Shima M, Takeyama M. Higher recovery of factor VIII (FVIII) with intermediate FVIII/von Willebrand factor concentrate than with recombinant FVIII in a haemophilia A patient with an inhibitor. Haemophilia 2006, 12:110-3.
99. Auerswald G, Spranger T, Brackmann HH. The role of plasma-derived factor VIII/von Willebrand factor concentrates in the treatment of hemophilia A patients. Haematologica 2003, 88:EREP05.
100. Scandella D, Gilbert GE, Shima M. Some factor VIII inhibitor antibodies recognize a common epitope corresponding to C2 domain amino acids 2248 through 2312, which overlap a phospholipid-binding site. Blood 1995, 86:1811-9.
101. Jacquemin M, Benhida A, Peerlinck K. A human antibody directed to the factor VIII C1 domain inhibits factor VIII cofactor activity and binding to von Willebrand factor. Blood 2000, 95:156-63.
102. Dasgupta S, Repesse Y, Bayry J. VWF protects FVIII from endocytosis by dendritic cells and subsequent presentation to immune effectors. Blood 2007, 109:610-2.
103. Dasgupta S, Navarrete AM, Bayry J. A role for exposed mannosylations in presentation of human therapeutic self-proteins to CD4+ T lymphocytes. Proc Natl Acad Sci U S A 2007, 104:8965-70.
104. Kaveri SV, Dasgupta S, Andre S. Factor VIII inhibitors: role of von Willebrand factor on the uptake of factor VIII by dendritic cells. Haemophilia 2007, 13(Suppl. 5):61-4.
105. Murphy SL, High KA. Gene therapy for haemophilia. Br J Haematol 2008, 140:479-87.
106. Rosenberg JB, Greengard JS, Montgomery RR. Genetic induction of a releasable pool of factor VIII in human endothelial cells. Arterioscler Thromb Vasc Biol 2000, 20:2689-95.
107. Yarovoi HV, Kufrin D, Eslin DE. Factor VIII ectopically expressed in platelets: efficacy in hemophilia A treatment. Blood 2003, 102:4006-13.
108. Gewirtz J, Thornton MA, Rauova L, Poncz M. Platelet-delivered factor VIII provides limited resistance to anti-factor VIII inhibitors. J Thromb Haemost 2008, 6:1160-6.
109. Shi Q, Wilcox DA, Fahs SA. Factor VIII ectopically targeted to platelets is therapeutic in hemophilia A with high-titer inhibitory antibodies. J Clin Invest 2006, 116:1974-82.
110. Yarovoi H, Nurden AT, Montgomery RR, Nurden P, Poncz M. Intracellular interaction of von Willebrand factor and factor VIII depends on cellular context: lessons from platelet-expressed factor VIII. Blood 2005, 105:4674-6.