ライフサイエンスコーパス: factor VIII

1 determinant in the clearance of coagulation factor VIII.

2 ith platelet GPIbalpha and collagen and with factor VIII.

3 oimmune disease caused by an autoantibody to factor VIII.

4 ilia A is hampered by the short half-life of factor VIII.

5 the apparent membrane affinity for wild-type factor VIII.

6 des promoting platelet adhesion, VWF carries Factor VIII.

7 mpairment of mutants compared with wild-type factor VIII.

8 D'D3 forms the binding site for factor VIII.

9 taining von Willebrand factor or recombinant factor VIII.

10 hibitors than those treated with recombinant factor VIII.

11 ent in patients with nonsevere hemophilia A (factor VIII 2-40 IU/dL).

12 the 125 patients treated with plasma-derived factor VIII (20 patients had high-titer inhibitors) and

13 of the 126 patients treated with recombinant factor VIII (30 patients had high-titer inhibitors).

14 to four times as long as that of recombinant factor VIII (37.6 hours vs. 9.1 hours in the lower-dose

15 ; FvW:ristocetin cofactor activity 44 IU/dL; factor VIII 99%; normal multimeric plasma vWF pattern) w

16 on of AAV8 or AAV9 vectors expressing canine factor VIII (AAV-cFVIII) corrected the FVIII deficiency

17 V5) vector encoding a B-domain-deleted human factor VIII (AAV5-hFVIII-SQ) in nine men with severe hem

18 von Willebrand factor propeptide (VWFpp) or factor VIII activity ( FVIII: C) and VWF antigen (VWF:Ag

19 nd subsequently alone, as long as hemostatic factor VIII activity (FVIII : C) levels were maintained.

20 ment was performed for VWF antigen (VWF:Ag), factor VIII activity (FVIII:C), blood group, and age.

21 Factor VIII activity declined at 4 and 6 hours (p < 0.05

22 sociated with the sustained normalization of factor VIII activity level over a period of 1 year in si

23 In the high-dose cohort, the factor VIII activity level was more than 5 IU per decili

24 Factor VIII activity levels remained at 3 IU or less per

25 ection of BIVV001 resulted in high sustained factor VIII activity levels, with a half-life that was u

26 alf-life ceiling and maintain high sustained factor VIII activity levels.

27 von Willebrand factor propeptide (VWFpp) or factor VIII activity to VWF antigen.

28 CES and LAS, but not with SVS (e.g. reduced factor VIII activity with AIS/CES/LAS; raised factor VII

29 nsecutive patients with severe hemophilia A (factor VIII activity, <0.01 IU per milliliter) who were

30 o 65 years of age) with severe hemophilia A (factor VIII activity, <1%) to receive a single intraveno

31 The development of neutralizing anti-factor VIII alloantibodies (inhibitors) in patients with

32 es the half-life associated with recombinant factor VIII, an increase that could signal a new class o

33 rval [CI], 18.4 to 35.2) with plasma-derived factor VIII and 44.5% (95% CI, 34.7 to 54.3) with recomb

34 It serves as a carrier for factor VIII and acts as a vascular damage sensor by attr

35 hrombin split products, D-dimer, P-selectin, factor VIII and C-reactive protein.

36 aining of the selected histologic slide with factor VIII and CD105 antigens by using Spearmen rank co

37 Factor VIII and factor V share structural homology and b

38 emostasis assessment included pro-coagulant (factor VIII and factor XIII) and anti-coagulant (protein

39 ondary prevention of ischaemic stroke, while factor VIII and gamma' fibrinogen require further popula

40 severe hemophilia (n = 4899 men with severe factor VIII and IX deficiency).

41 ailable genomic sequence data on coagulation factor VIII and predictive models of molecular evolution

42 and soluble P-selectin and also for clotting factor VIII and the thrombin generation potential.

43 nous thrombosis risk via concurrently raised factor VIII and von Willebrand factor levels.

44 dominance effects only at the ABO locus for factor VIII and von Willebrand factor.

45 ng kidney function in controls, most notably factor VIII and von Willebrand factor.

46 o, we achieved long-term expression of human factors VIII and IX (hFVIII and hFIX) in mouse models of

47 pressed inhibitor formation directed against factors VIII and IX and anaphylaxis against factor IX (F

48 ciency or dysfunction of coagulation protein factors VIII and IX, respectively.

49 mas from hemophilia A or C patients who lack factors VIII and XI, which are mediators of the two prin

50 to cleave substrates, including fibrinogen, factor VIII, and PAR1.

51 Increase in fibrinogen, factor VIII, and von Willebrand factor and decrease in a

52 everal studies showed that neutralizing anti-factor VIII (anti-fVIII) antibodies (inhibitors) in pati

53 actor VIII activity with AIS/CES/LAS; raised factor VIII antigen with AIS/CES; and increased factor X

54 Using coagulation factor VIII as a model ligand, we now study the contribu

55 Recombinant factor VIII as well as bypassing agents and immune toler

56 single intravenous injection of recombinant factor VIII at a dose of 25 IU per kilogram of body weig

57 The boy had hemophilia due to a factor VIII autoantibody and nephrotic syndrome.

58 n, indicate an influence of the C1 domain on factor VIII binding to factor X, and indicate that coope

59 ase mutations, including those that diminish factor VIII binding, which suggest that factor VIII bind

60 nish factor VIII binding, which suggest that factor VIII binds not only to the N-terminal TIL' domain

61 Factor VIII binds to phosphatidylserine (PS)-containing

62 ody BO2C11 decreased the V(max) of wild-type factor VIII by 90% but decreased the activity of 3 mutan

63 ults identify a membrane-binding face of the factor VIII C1 domain, indicate an influence of the C1 d

64 We prepared 4 factor VIII C1 mutations localized to a hypothesized mem

65 e an x-ray crystallographic structure of the factor VIII C2 domain in complex with 2 antibodies that

66 The factor VIII C2 domain is a highly immunogenic domain, wh

67 recognizes epitopes on opposing faces of the factor VIII C2 domain.

68 al" types of antibody inhibitors against the factor VIII C2 domain.

69 ciency virus type 1 antigens and coagulation factor VIII captured on the cantilever in the presence o

70 (VWF:Act), antigen (VWF:Ag), multimers, and factor VIII coagulant activity were virtually absent.

71 nts with hemophilia B, the large size of the factor VIII coding region has precluded improved outcome

72 philia A, and no previous treatment with any factor VIII concentrate or only minimal treatment with b

73 -frozen plasma (FFP) and intermediate purity factor VIII concentrate were used as treatment.

74 data that take exposure days to therapeutic factor VIII concentrates into account.

75 In congenital VWD, prophylaxis with VWF/factor VIII concentrates is generally started after GI-b

76 py with plasma-derived von Willebrand factor-factor VIII concentrates represents the safe mainstay of

77 llance studies for all of the new engineered factor VIII concentrates with prolonged half-lives that

78 n (DDAVP) and/or von Willebrand factor (VWF)/factor VIII concentrates.

79 Patients treated with plasma-derived factor VIII containing von Willebrand factor had a lower

80 s among patients treated with plasma-derived factor VIII containing von Willebrand factor or recombin

81 Murine models of combined TFPI and factor VIII deficiency were used to examine the impact o

82 Near-to-complete correction of hemophilia A (factor VIII deficiency) and hemophilia B (factor IX defi

83 Coagulation factor VIII deficient (FVIII(-/-)) mice develop an osteo

84 Repeated infusions of recombinant Factor VIII did not rescue thrombosis in VWF(-/-) mice,

85 s of a model protein substrate, procoagulant factor VIII, did not correlate with that of PFR-MCA prio

86 an second-generation full-length recombinant factor VIII, effect estimates remained similar for all i

87 eived 4x10(13) vg per kilogram) had a median factor VIII expression of 13 IU per deciliter; the media

88 eived 6x10(13) vg per kilogram) had a median factor VIII expression of 20 IU per deciliter; the media

89 o had received 2x10(13) vg per kilogram) had factor VIII expression of less than 1 IU per deciliter,

90 ith animal growth to 5 wk of age with stable factor VIII expression thereafter to >1 y of age.

91 Decline in factor VIII expression was not related to cell-mediated

92 f choices among several commercial brands of factor VIII extracted from human plasma or engineered fr

93 Combined deficiency of factor V and factor VIII (F5F8D) is a bleeding disorder caused by mut

94 (FVIII) deficiency caused by mutation in the factor VIII (F8) gene.

95 comprehensively the bone health of clotting factor VIII, factor IX, and Von Willebrand Factor knocko

96 In a mechanism distinct from factor VIII, factor V activation involves proteolytic re

97 A recombinant factor VIII-Fc fusion protein (rFVIIIFc) was constructed

98 Neutralizing antibodies (inhibitors) toward factor VIII form a severe complication in nonsevere hemo

99 We previously demonstrated that coagulation factor VIII (FVIII) accelerates proteolytic cleavage of

100 Further testing revealed factor VIII (FVIII) activity of 16%, factor IX (FIX) act

101 e development of alloantibodies that inhibit factor VIII (FVIII) activity, Hay and DiMichele compared

102 ilia A and B, diseases caused by the lack of factor VIII (FVIII) and factor IX (FIX) respectively, le

103 B are caused by deficiencies in coagulation factor VIII (FVIII) and factor IX, respectively, resulti

104 Factor VIII (FVIII) and its carrier protein von Willebra

105 brinogen, coagulation factor VII (FVII), and factor VIII (FVIII) and its carrier von Willebrand facto

106 we demonstrate that the interaction between factor VIII (FVIII) and LRP1 occurs over an extended sur

107 is due to autoantibodies against coagulation factor VIII (FVIII) and most often presents with unexpec

108 Plasma factor VIII (FVIII) and von Willebrand factor (VWF) circ

109 Complex formation between coagulation factor VIII (FVIII) and von Willebrand factor (VWF) is o

110 investigations into the interaction between factor VIII (FVIII) and von Willebrand factor (VWF).

111 ic response to vascular injury requires both factor VIII (FVIII) and von Willebrand factor (VWF).

112 ence a higher incidence of neutralizing anti-factor VIII (FVIII) antibodies ("inhibitors") vis-a-vis

113 severe hemophilia A develop inhibitory anti-factor VIII (fVIII) antibodies (Abs).

114 Neutralizing anti-factor VIII (FVIII) antibodies that develop in patients

115 with hemophilia A is the development of anti-factor VIII (fVIII) antibodies.

116 Inhibitory antibodies to factor VIII (FVIII) are a major complication in the trea

117 The primary B-cell epitopes of factor VIII (fVIII) are in the A2 and C2 domains.

118 Frequent infusions of intravenous factor VIII (FVIII) are required to prevent bleeding ass

119 A long-acting factor VIII (FVIII) as a replacement therapy for hemophi

120 hestrate hemostatic processes, in particular factor VIII (FVIII) binding and stabilization in plasma,

121 The primary cellular source of factor VIII (FVIII) biosynthesis is controversial, with

122 e uptake and processing of blood coagulation factor VIII (FVIII) by antigen-presenting cells and the

123 s may avoid inhibitory antibody formation to factor VIII (FVIII) by taking advantage of immune immatu

124 Factor VIII (FVIII) consists of a heavy (A1A2B domains)

125 Factor VIII (FVIII) consists of a heavy chain (A1(a1)A2(

126 The factor VIII (FVIII) crystal structure suggests a possibl

127 is a monogenic disease with a blood clotting factor VIII (FVIII) deficiency caused by mutation in the

128 Human and porcine coagulation factor VIII (fVIII) display a biosynthetic efficiency di

129 -based gene therapies can restore endogenous factor VIII (FVIII) expression in hemophilia A (HA).

130 illebrand factor (VWF) D'D3 domains protects factor VIII (FVIII) from rapid clearance.

131 wn to mediate clearance of blood coagulation factor VIII (FVIII) from the circulation.

132 Factor VIII (FVIII) functions as a cofactor for factor I

133 Membrane-bound Factor VIII (FVIII) has a critical function in blood coa

134 The C1 domain of factor VIII (FVIII) has been implicated in binding to mu

135 III (rFVIII), comprised of covalently bonded factor VIII (FVIII) heavy and light chains.

136 risk factors for the initiation of the anti-factor VIII (FVIII) immune response seen in 25% to 30% o

137 f B-cell depletion on tolerance induction to factor VIII (FVIII) in a mouse model of hemophilia A.

138 in of von Willebrand factor (VWF) stabilizes factor VIII (FVIII) in the circulation and maintains it

139 et al provide evidence that the high rate of factor VIII (FVIII) inhibitors seen in black hemophilia

140 a A of all ages with and without coagulation factor VIII (FVIII) inhibitors.

141 ral cell type(s) that synthesize and release factor VIII (FVIII) into the circulation are still not k

142 The development of inhibitory antibodies to factor VIII (FVIII) is a major obstacle in using this cl

143 Recombinant canine B-domain deleted (BDD) factor VIII (FVIII) is predominantly expressed as a sing

144 ating hemophilia A patients with therapeutic factor VIII (FVIII) is that 20% to 30% of these patients

145 antibodies (inhibitors) against coagulation factor VIII (FVIII) is the most problematic and costly c

146 Replacement therapy with factor VIII (FVIII) is used in patients with hemophilia

147 ariants with von Willebrand factor (VWF) and factor VIII (FVIII) levels in 4468 AAs.

148 The development of anti-factor VIII (FVIII) neutralizing antibodies (inhibitors)

149 Thrombin-catalyzed activation of factor VIII (FVIII) occurs through proteolysis at three

150 ia is treated by IV replacement therapy with Factor VIII (FVIII) or Factor IX (FIX), either on demand

151 haracterized by deficiencies in procoagulant factor VIII (FVIII) or factor IX (FIX), respectively.

152 Previous studies have demonstrated that factor VIII (FVIII) or platelets alone increase cleavage

153 Factor VIII (FVIII) pharmacokinetic (PK) properties show

154 data after the infusion of a new recombinant factor VIII (FVIII) product that when fused with the Fc

155 Current factor VIII (FVIII) products display a half-life (t(1/2)

156 poses a challenge for optimal treatment with factor VIII (FVIII) products.

157 ent of neutralizing Abs to blood coagulation factor VIII (FVIII) provides a major complication in hem

158 Neutralizing antibodies against factor VIII (FVIII) remain the major complication in the

159 The cellular source of coagulation factor VIII (FVIII) remains controversial.

160 ch have established the relationship between factor VIII (FVIII) replacement levels and bleeding risk

161 Factor VIII (FVIII) replacement products enable comprehe

162 Although factor VIII (FVIII) replacement therapy can be lifesavin

163 lopment of neutralizing antibodies following factor VIII (FVIII) replacement therapy for hemophilia A

164 emophilia A, the most severe complication of factor VIII (FVIII) replacement therapy involves the for

165 acid substitution N1922S in the A3 domain of factor VIII (fVIII) results in moderate to severe hemoph

166 et al demonstrate that platelets expressing factor VIII (FVIII) shield FVIII from immune detection.

167 The liver is a major factor VIII (FVIII) synthesis site, and mesenchymal stem

168 sorder caused by a deficiency in coagulation factor VIII (fVIII) that affects 1 in 5,000 males.

169 ost feared treatment-related complication of factor VIII (fVIII) therapy.

170 treatment, ranging from high-dose intensive factor VIII (FVIII) treatment to prophylactic treatment,

171 s to describe the relationships of the PK of factor VIII (FVIII) with age and body weight by a popula

172 These approaches include factor VIII (FVIII) with extended half-life (eg, FVIII-F

173 Studies have correlated elevated plasma factor VIII (FVIII) with thrombosis; however, it is uncl

174 Neutralizing autoantibodies against factor VIII (FVIII), also called FVIII inhibitors, are t

175 Administration of recombinant factor VIII (FVIII), an important co-factor in blood clo

176 dylserine (PS) but express binding sites for factor VIII (fVIII), casting doubt on the role of expose

177 e protease factor IX (FIX) and its cofactor, factor VIII (FVIII), is crucial for propagation of the i

178 ed bleeding disorder caused by deficiency of factor VIII (FVIII), is treated by protein replacement.

179 erves as the carrier protein for coagulation factor VIII (FVIII), protecting it from proteolytic degr

180 ent of smaller expression cassettes encoding factor VIII (FVIII), which demonstrate improved biosynth

181 ron-22-inversion patients express the entire Factor VIII (FVIII)-amino-acid sequence intracellularly

182 lebrand factor (VWF) fragment containing the factor VIII (FVIII)-binding D'D3 region of VWF is suffic

183 een shown to increase the clot lysis time in factor VIII (fVIII)-deficient plasma by an activated thr

184 Previously, we delivered autologous factor VIII (FVIII)-expressing blood outgrowth endotheli

185 Factor VIII (FVIII)-neutralizing antibodies ("inhibitors

186 globulin (Ig) isotypes and IgG subclasses of factor VIII (FVIII)-specific antibodies are found in dif

187 Such engineered factor VIII (FVIII)-specific Tregs efficiently suppresse

188 A (AHA) is caused by autoantibodies against factor VIII (FVIII).

189 disorder caused by deficiency of coagulation factor VIII (FVIII).

190 of inhibitor antibodies against coagulation factor VIII (fVIII).

191 ion of recombinant clotting factors, such as factor VIII (FVIII).

192 izing antibodies (inhibitors) to replacement factor VIII (FVIII, either plasma derived or recombinant

193 d VWF antigen (VWF:Ag) and the ratio between factor VIII (FVIII:C) and VWF:Ag may be used to assess s

194 the combined deficiency of factor V (FV) and factor VIII (FVIII; F5F8D), suggesting an ER-to-Golgi ca

195 actor IX (FIXa) with its cofactor, activated factor VIII (FVIIIa) is a crucial event in the coagulati

196 A2 domain rapidly dissociates from activated factor VIII (FVIIIa) resulting in a dampening of the act

197 ntribute to A2 domain retention in activated factor VIII (FVIIIa).

198 model in which exons 17 and 18 of the murine factor VIII gene (F8) are flanked by loxP sites, or flox

199 gest that bleeding phenotype correlates with factor VIII gene (F8) mutation type.

200 against vectors and by the large size of the factor VIII gene.

201 alternative treatment options to prolong the factor VIII half-life, and delineate the role of VWF and

202 an 87% higher incidence than plasma-derived factor VIII (hazard ratio, 1.87; 95% CI, 1.17 to 2.96).

203 plant species eliminated 105 (human clotting factor VIII heavy chain [FVIII HC]) and 59 (polio VIRAL

204 Transgene-derived human factor VIII (hFVIII) protein activity mirrored native hF

205 sociated virus (rAAV) vectors encoding human factor VIII (hFVIII) were systematically evaluated for h

206 otential complexities of the polyclonal anti-factor VIII immune response and further define the "clas

207 , and antibody responses against coagulation factor VIII in hemophilia A mice, even in animals previo

208 rminants of development of inhibitory Abs to factor VIII in people with hemophilia A indicate a compl

209 ematoma with midline shift, a single dose of factor VIII inhibitor bypassing activity (25 U/kg) was a

210 lation tests following the administration of factor VIII inhibitor bypassing activity and a follow-up

211 Factor VIII inhibitor bypassing activity may be a viable

212 randomized trial to assess the incidence of factor VIII inhibitors among patients treated with plasm

213 o explore the natural history of later-onset factor VIII inhibitors and to investigate other potentia

214 Patients with severe hemophilia A and factor VIII inhibitors are at increased risk for serious

215 Factor VIII inhibitors arise in patients with hemophilia

216 The age-adjusted incidence of new factor VIII inhibitors was analyzed in all United Kingdo

217 on in an NHP model of hemophilia A with anti-factor VIII inhibitors.

218 nts in patients with severe hemophilia A and factor VIII inhibitors.

219 ices are price and the risk of occurrence of factor VIII inhibitory alloantibodies.

220 egimens for patients with severe hemophilia (factor VIII/IX < 1 IU/dL) born between 1970 and 1994, us

221 Bleeding in hemophilia is the result of factor VIII/IX deficiency with corresponding reduced thr

222 g quantified proteins C and S, antithrombin, factors VIII/IX/XI, fibrinogen, lipoprotein(a), homocyst

223 alysis of hematopoietic stem cells (HSCs) in factor VIII knockout (FVIIIKO) mice revealed a novel reg

224 The average factor VIII level in this group was 99 IU/dL, suggesting

225 f BIVV001 in the higher-dose group, the mean factor VIII level was in the normal range (>=51%) for 4

226 sults in 15 adults with severe hemophilia A (factor VIII level, <=1 IU per deciliter) who had receive

227 We evaluated the factor VIII level, annualized rate of bleeding events, u

228 e-matched analysis controlling for age, sex, factor VIII level, inhibitor titer, and underlying etiol

229 Compared with eGFR >50th percentile, factor VIII levels (adjusted mean difference, 60 IU/dL f

230 otypic remission 1 with normalization of VWF/factor VIII levels and multimer pattern.

231 inhibitor development in mild hemophilia A (factor VIII levels between 5 and 40 U/dL) is larger than

232 plasma von Willebrand factor and coagulation factor VIII levels in GWAS, suggesting that haploinsuffi

233 tor tests with decreased in vivo recovery of factor VIII levels.

234 leukoreduced red blood cells and coagulation factor VIII manufactured from blood of United Kingdom do

235 Milk fat globule-epidermal growth factor-factor VIII (MFG-E8), a membrane-associated secretory gl

236 or capsids, the utilization of factor IX and factor VIII modified transgenes to improve secretion or

237 on (70%), defined as inhibitor undetectable, factor VIII more than 70 IU/dL and immunosuppression sto

238 Factor VIII mutants were active on additional membrane s

239 In breeding studies, Factor VIII null (F8(-/-)) did not rescue the embryonic

240 iency of intrinsic blood coagulation pathway factor VIII or IX, pharmacological agents that inactivat

241 Adjustment for factor VIII or von Willebrand factor attenuated these od

242 Inhibitory antibodies to factors VIII or IX represent a serious complication for

243 a bleeding disorder caused by deficiency in factors VIII or IX, the two components of the intrinsic

244 celerin (factor V), antihemophilic globulin (factor VIII), or Christmas factor (factor IX), Rapaport

245 n of a misfolding-prone human blood clotting factor VIII, or after partial hepatectomy.

246 ich cannot bind platelets, blood coagulation factor VIII, or collagen, causing VWD through dominant-n

247 on Willebrand factor (p = 4.7 x 10(-57)) and factor VIII (p = 1.2 x 10(-36)).

248 The factor VIII pharmacodynamic profiles reflected cellular

249 in, fibrinogen, total homocysteine, D-dimer, factor VIII, plasmin-antiplasmin complex, and inflammati

250 We assessed von Willebrand factor (VWF), factor VIII, platelet activation and aggregation, platel

251 factors is counterbalanced by an increase in factor VIII (produced by liver sinusoidal endothelial ce

252 ophilia A, it is unclear whether the type of factor VIII product administered and switching among pro

253 Recombinant and plasma-derived factor VIII products conferred similar risks of inhibito

254 n the analysis was restricted to recombinant factor VIII products other than second-generation full-l

255 using synthetic peptides from regions of the Factor VIII protein where ns-SNPs occur and showed that

256 of neutralizing anti-drug-antibodies to the Factor VIII protein-therapeutic is currently the most si

257 nectin and milk-fat globule epidermal growth factor VIII protein.

258 found in all racial groups and are the only factor VIII proteins found in the white population to da

259 development of antibodies to capsid or human factor VIII proteins.

260 The half-life of recombinant factor VIII ranges from 15 to 19 hours because of the vo

261 /d) and low-dose (LD; 50 IU/kg 3 times/week) factor VIII regimens in 115 "good-risk," severe high-tit

262 while differentiated EC clusters (expressing factor VIII related antigen (RA)) increased by 25% (p <

263 he expression of a specific vascular marker, factor VIII-related antigen (FVIII-RAg), and several cel

264 al measurements of vessel density, and found factor VIII-related antigen levels to correlate with the

265 riations in vessel density by measurement of factor VIII-related antigen, we found KLK6 protein and m

266 the Bristol (UK) samples, by measurement of factor VIII-related antigen, which we showed to correlat

267 Factor VIII replacement products have improved the care

268 reby inhibitory antibodies develop following factor VIII replacement therapy for congenital hemophili

269 an increase that could signal a new class of factor VIII replacement therapy with a weekly treatment

270 profiles, and leads to a return to a normal factor VIII response in approximately 60% of patients.

271 ially administered together with recombinant factor VIII (rFVIII) and subsequently alone, as long as

272 The effect of recombinant factor VIII (rFVIII) brand on inhibitor development was

273 d phase 3 multicenter study of a recombinant factor VIII (rFVIII) product fused with the Fc fragment

274 Six recombinant factor VIII (rFVIII) products have been marketed worldwi

275 sk of inhibitor development with recombinant factor VIII (rFVIII) than plasma-derived concentrates (p

276 ) combined at a fixed ratio with recombinant factor VIII (rFVIII) were investigated in 32 subjects wi

277 in is a novel B-domain-truncated recombinant factor VIII (rFVIII), comprised of covalently bonded fac

278 , annualized rate of bleeding events, use of factor VIII, safety, expression kinetics, and biologic m

279 l-length complementary DNA sequence of human factor VIII), second-generation full-length products wer

280 f anti-C2 inhibitory antibodies that bind to factor VIII simultaneously was investigated by x-ray cry

281 4.5% (95% CI, 34.7 to 54.3) with recombinant factor VIII; the cumulative incidence of high-titer inhi

282 ; falls in thrombin generation, Factor V and Factor VIII to 52%, 19% and 17% normal respectively; fur

283 mune tolerance induction with large doses of factor VIII to eradicate inhibitors.

284 Patients with hemophilia A rely on exogenous factor VIII to prevent bleeding in joints, soft tissue,

285 Plasma factor VIII to VWF antigen (VWF:Ag) ratios were signific

286 he study to 1 event after gene transfer, and factor VIII use for participant-reported bleeding ceased

287 vents and complete cessation of prophylactic factor VIII use in all participants who had received 4x1

288 on of hemostasis and a profound reduction in factor VIII use in all seven participants.

289 tested (interleukin-6, d-dimer, coagulation factor VIII, von Willebrand factor, and homocysteine).

290 The patient received factor VIII/vWF concentrate both during and after surger

291 dependent adenoviral vector expressing human factor VIII was administered i.v. to neonatal hemophilia

292 ary end point of all inhibitors, recombinant factor VIII was associated with an 87% higher incidence

293 Regarding coagulation factors, factor VIII was higher, whereas protein C, protein S, an

294 vents was 0, and the median use of exogenous factor VIII was reduced from 138.5 infusions to 0 infusi

295 bleeding events was 0, and the median use of factor VIII was reduced from 155.5 infusions to 0.5 infu

296 No inhibitors to factor VIII were detected and no hypersensitivity or ana

297 No neutralizing antibodies to factor VIII were detected.

298 to induce clotting and activate factor V and factor VIII with rates similar to the plasma-derived mol

299 , we hypothesize that storage of coagulation Factor VIII within platelets may provide a locally induc

300 as operational tolerance was established to factor VIII without development of inhibitors; however,