ライフサイエンスコーパス: FXa

1 FXa also cleaves FVIII/FVIIIa at Arg(336) and Arg(562) r

2 FXa and the noncanonical PAR3 tethered-ligand peptide in

3 FXa generation assays and Western blotting, used to moni

4 FXa inhibition and PAR-2 deficiency in nonhematopoietic

5 FXa signalling via activation of protease-activated rece

6 FXa(I16L) also reduces the anticoagulant-associated blee

7 FXa(I16L) may be able to fill an important unmet clinica

8 FXa(I16L) may provide an effective strategy to enhance b

9 des, FVa residues 493-506 were proposed as a FXa binding site.

10 Xa's active site serine was depolarized in a FXa concentration-dependent fashion in the presence of m

11 ion, ZPI-CD-helix(alpha1-PI) inhibition of a FXa mutant containing a mutation in the heparin-binding

12 ssociated factor V(a) (FVa) and factor X(a) (FXa) serve as the essential prothrombin-activating compl

13 ts such that structural data on PS-activated FXa is required to understand the structure of the FXa d

14 FXI (FXIa) is FIX, leading to FX activation (FXa) and thrombin generation.

15 Because of its inherent catalytic activity, FXa(I16L) is more potent (by >50-fold) in the hemostasis

16 rs, though with moderate selectivity against FXa.

17 -specific fluorescent derivatives of FVa and FXa after laser injury in the mouse cremaster arteriole.

18 heir cell membranes, thus generating FVa and FXa binding sites and mediating the formation of fibrin.

19 Although bound FVa and FXa may have been present on the platelet core at the ni

20 te high affinity association between FVa and FXa.

21 resistant to direct cleavage by TF:FVIIa and FXa was activated by these proteases when cells co-expre

22 physiological concentrations of TF:FVIIa and FXa.

23 ous "caps" with increased Annexin V, FX, and FXa binding were observed, indicating relevance of this

24 required for optimal inhibition of FXIa and FXa.

25 ed intracellular Ca(2+) release in HUVEC and FXa reactive IgG from patients with APS and/or SLE poten

26 In hemophilic plasma, FXa(I16L) and FXa(V17A) have prolonged half-lives compared with wild-t

27 Notably, assembly of FXa(I16L) and FXa(V17A) on activated platelets with factor Va to form

28 with zymogen-like properties (FXa(I16L) and FXa(V17A)) circumvent these limitations.

29 factor X through mutagenesis (FXa(I16L) and FXa(V17A)) not only alters active site function, but als

30 mpared to healthy control subjects' IgG, and FXa alone.

31 interfere with inactivation of thrombin and FXa by antithrombin (AT).

32 sions and their main activators thrombin and FXa in the plaque were determined in the plaque.

33 n of PARs and their activators, thrombin and FXa was diminished after rivaroxaban treatment.

34 FIXa) is homologous to those of thrombin and FXa, we hypothesized that some aPLs in APS bind to FIXa

35 o FXa and that the levels of plasma IgG anti-FXa Ab in 38 APS patients were significantly higher than

36 pid Ab with FXa and the presence of IgG anti-FXa Ab in APS patients and investigated the effects of F

37 f, 5 of 38 APS patients (13.2%) had IgG anti-FXa Ab.

38 ide displayed a significantly increased anti-FXa activity compared with those of the pentasaccharide,

39 Despite the lower anti-FXa activity, dose reduction preserved the efficacy of e

40 L [22.7] to 16.0 ng/mL [14.5]) and mean anti-FXa activity by 25% (from 0.85 IU/mL [0.76] to 0.64 IU/m

41 fully-retained in the affinity purified anti-FXa IgG sub-fraction.

42 Combined, these results indicate that anti-FXa Ab may contribute to thrombosis by interfering with

43 igatran and the prothrombin time or the anti-FXa for rivaroxaban.

44 ts with data available) and mean trough anti-FXa activity (0.35-0.85 IU/mL in 2865 patients).

45 APC, FXa, and the noncanonical PAR3 tethered-ligand peptide i

46 ected behavior of an increase in activity as FXa bound to membranes, but instead suggested the existe

47 in FXI- or FIX-deficient plasma, as well as FXa-initiated clotting times in FX-deficient plasma.

48 ed to have different specificity for binding FXa and FIXa while retaining compatibility as substrate

49 In a model system, compound 3 blocked FXa inhibition by TFPI (EC50 = 11 nM) and inhibition of

50 ot detectable for FX, catalytic site-blocked FXa, thrombin, and 12 other enzymes.

51 novel antithrombotic peptide exhibiting both FXa inhibition and anti-platelet aggregation activities,

52 und that, albeit with different timing, both FXa/PCPS and E coli infusion led to robust thrombin and

53 equence LTFPRIVFVLG was identified with both FXa inhibition and anti-platelet aggregation activities.

54 lded a surprisingly modest decrease in bound FXa and FVa with little impact on fibrin formation.

55 ignificant inhibitor of prothrombinase-bound FXa during prothrombin activation.

56 coagulation as well as prothrombinase-bound FXa in the propagation phase that complement prothrombin

57 Zn(2+)-containing PS bound FXa more efficiently (K(d)(app)=9.3 nM) than Zn(2+)-defi

58 e activity and structure of human and bovine FXa.

59 n factor V (FV), which has been activated by FXa.

60 Tie2 activation by FXa required PAR3 and EPCR.

61 ting and inactivating cleavages catalyzed by FXa that is modulated in large part by sequences flankin

62 n of EPCR promoted PAR1 and PAR2 cleavage by FXa in the ternary complex but did not alter PAR2 cleava

63 hether prothrombin was activated directly by FXa or through extrinsic or intrinsic pathway activators

64 each of the above antibodies was examined by FXa generation assays.

65 Factor (F)VIII can be activated to FVIIIa by FXa following cleavages at Arg(372), Arg(740), and Arg(1

66 and directly inhibits thrombin generated by FXa/FVa (prothrombinase complex).

67 ever, the activity of DeltaC2 as measured by FXa generation and one-stage clotting assays retained 76

68 olecule-1 in sickle mice was not mediated by FXa or thrombin.

69 ility of pre-existing plaques was reduced by FXa inhibition as reflected by reduced macrophages (-39.

70 ion-dependent induction of Ca(2+) release by FXa that was potentiated by APS-IgG and SLE/APS- IgG com

71 of activation of prothrombin to thrombin by FXa in the presence of 400 muM C6PS by 14 000- to 15 000

72 Using pure component FXa inhibition assays, we found that although FV alone d

73 e inhibitor to hinder antithrombin-dependent FXa inactivation, paradoxically allowing uninhibited FXa

74 ssue factor-factor VIIa (TF-FVIIa)-dependent FXa generation.

75 These data implicate FcRn in TF-dependent FXa activity induced by soluble and cell-associated IgG-

76 sed blood coagulation scheme in which direct FXa-mediated FV activation occurs in the initiation phas

77 sis than the dysregulation of the downstream FXa and thrombin.

78 ing reciprocal activation of FVII/TF by each FXa mutant were impaired.

79 (2+) is required for PS-direct and efficient FXa binding and may play a role in stabilizing PS confor

80 Protein S enhances FXa inhibition by TFPIalpha.

81 f K3 (R199L, TFPI(K3P1)) produced equivalent FXa inhibition in the absence of PS, whereas the respons

82 n that is strongly implicated as an extended FXa binding surface in the prothrombinase complex.

83 , we show that a variant coagulation factor, FXa(I16L), rapidly restores hemostasis in the presence o

84 to simulate intraclot generation of: Factors FXa (via TF/VIIa or FIXa), FIXa (via TF/FVIIa or FXIa),

85 All of them, including factors IXa (FIXa), FXa/FX, FVa, FVIII, prothrombin, and PS-sensitive marker

86 ctivity of FIXa with AT, we prepared an FIXa/FXa chimera in which the 39-loop of the protease was rep

87 (increasing FXa concentration) and at fixed FXa concentration (increasing membrane concentration).

88 lar FXIa inhibitory activity with >1000-fold FXa selectivity and >100-fold thrombin selectivity.

89 cal vein endothelial cells (HUVEC) following FXa-mediated PAR activation and investigated whether FXa

90 % clotting activity and reduced affinity for FXa membranes (approximately 20-fold) and did not bind t

91 utant had significantly reduced affinity for FXa.

92 important for FVIIa inhibition but also for FXa inhibition, i.e. for the transition of the loose to

93 The capacity for FXa to activate FVIII variants where cleavage at Arg(336

94 itically reduces the inhibition constant for FXa to below the plasma concentration of TFPI.

95 o unveil a high affinity binding site(s) for FXa.

96 ependent factor Xa (FXa) generation and free FXa.

97 r the ZPI-PZ complex in regulating both free FXa generated in the initiation phase of coagulation as

98 a TF-FVIIa mutant complex with impaired free FXa generation but activating both FVIII and FIX support

99 s are activated to produce its cofactor FVa, FXa(I16L) is driven to the protease state and restores h

100 6PS) triggers assembly of a fully active FVa-FXa complex in solution and (2) that 2 molecules of C6PS

101 Ca(2+) to show that the apparent K(d) of FVa-FXa interaction increased with an increase in FXa concen

102 that are selectively activated by TF:FVIIa, FXa, and thrombin.

103 ocked PAR activation by the ternary TF-FVIIa-FXa complex but not by the non-coagulant TF-FVIIa binary

104 activity and the colocalization of TF-FVIIa-FXa-TFPI with caveolin-1.

105 a cross-talk between EPCR and an unknown FX/FXa receptor, which does not require interaction with th

106 determined the proteolytic activity of human FXa toward human Pre2 as a substrate both at fixed membr

107 Here, we identified FXa as potent platelet agonist that acts through PAR-1.

108 In this study, we identified FXa as potent, direct agonist of the PAR-1 (protease-act

109 required to explore the potential use of IgG FXa reactivity as a novel biomarker to stratify treatmen

110 In FXa-catalyzed prothrombin activation assays, both FV and

111 This loop is highly acidic in FXa, containing three Glu residues at positions 36, 37,

112 to heparin (K(D) ~ 20 nM), but no change in FXa inhibition was observed in the presence of the cofac

113 ing and enhancement of TFPI was confirmed in FXa inhibition assays and using surface plasmon resonanc

114 loro- versus methyl-substituted P1 groups in FXa, which extends beyond the current series.

115 Xa interaction increased with an increase in FXa concentration at 5 mM Ca(2+), but the K(d) was only

116 conclusion, PAR-1 and PAR-2 are involved in FXa-mediated intracellular Ca(2+) release in HUVEC and F

117 This loop in FXa is highly acidic and contains three Glu residues at

118 n the absence of PS, whereas the response in FXa inhibition produced by PS was reduced with TFPI(K3P1

119 d the FV acidic region, which is retained in FXa-activated FVa and platelet FVa.

120 olytic activity and formation of an inactive FXa dimer in solution.

121 branes also trigger formation of an inactive FXa dimer.

122 APS-IgG and SLE/APS- IgG increased FXa mediated NFkappaB signalling and this effect was ful

123 tes TFPI and ADTRP expression, and increases FXa inhibition by TFPI in an ADTRP- and caveolin-1-depen

124 .04, when FXa/FVa is 1:4, with an increasing FXa and substrate concentration.

125 at fixed membrane concentration (increasing FXa concentration) and at fixed FXa concentration (incre

126 g ICs that bind to FcgammaR and FcRn induced FXa activity, whereas IgG-containing ICs with an Fc engi

127 Desmolaris also inhibits FXa with lower affinity, independently of protein S.

128 s FVIIa and the K2 domain similarly inhibits FXa.

129 , we report that TIX-5 specifically inhibits FXa-mediated FV activation involving the B domain of FV

130 x, but did not affect formation of the loose FXa-TFPI complex.

131 urther that the enhancement of TFPI-mediated FXa inhibition by protein S and FV depends on a direct p

132 ugh FV alone did not influence TFPI-mediated FXa inhibition, it further enhanced TFPI in the presence

133 We monitored FXa activity at 5, 20, and 50 nM FXa while titrating wit

134 transition in factor X through mutagenesis (FXa(I16L) and FXa(V17A)) not only alters active site fun

135 A mutant FXa (R165A) that has reduced prothrombinase activity sho

136 but preserving FVIIIa generation by nascent FXa, can support intrinsic pathway coagulation.

137 Moreover, nascent FXa product of TF-FVIIa can transiently escape the slow

138 A mixture of 50 nM FXa and 50 nM FVa in the presence of 400 muM C6PS yielde

139 e monitored FXa activity at 5, 20, and 50 nM FXa while titrating with FVa in the presence of 400 muM

140 Xa homodimers and Xa.Va heterodimers, but no FXa dimers bound to FVa.

141 The ability of FXa(I16L) to reverse the anticoagulant effects of FXa in

142 nd to enhance both the catalytic activity of FXa and the cofactor activity of FVa.

143 ke other serpins to regulate the activity of FXa but in a manner uniquely dependent on protein Z, pro

144 Alteration of FXa zymogenicity yields variants (V17M, I16L, I16M, V17T

145 Notably, assembly of FXa(I16L) and FXa(V17A) on activated platelets with fact

146 Binding of FXa active site-labeled with Oregon Green to FV and FVa

147 This new class of FXa variants provides a useful and flexible platform for

148 The combination of FXa and FVIIa maximally enhanced infection for TF(+)/gC(

149 specifically investigate the contribution of FXa and thrombin, mice were fed chow containing either r

150 nt, unlike the strict membrane dependence of FXa for high affinity FVa binding.

151 odel that takes into account dimerization of FXa after binding to a membrane, which yielded estimates

152 Here we ask whether dimerization of FXa and its binding to FVa in the presence of C6PS are c

153 ombinase assembly and possible disruption of FXa inhibition by the tissue factor pathway inhibitor.

154 are both located in the catalytic domain of FXa and that these sites are linked thermodynamically.

155 ally, TF or gC partly enhanced the effect of FXa, but not FVIIa, revealing gC as a novel PAR2 cofacto

156 Therefore, we investigated effects of FXa inhibition by rivaroxaban on both newly-formed and p

157 16L) to reverse the anticoagulant effects of FXa inhibitor depends, at least in part, on the ability

158 APS patients and investigated the effects of FXa-reactive mAb on AT inactivation of FXa.

159 a TFPI cofactor, enhancing the efficiency of FXa inhibition.

160 conclude that the PS-mediated enhancement of FXa inhibition by TFPI-alpha involves an interaction bet

161 istence of a membrane-bound inactive form of FXa.

162 esis showed that the GLA-EGF(NC) fragment of FXa (lacking the catalytic domain) neither dimerized nor

163 ACH-11 inhibited the catalytic function of FXa towards its substrate S-2222 via a mixed model with

164 cells with FXIa increased the generation of FXa and promoted TF-dependent fibrin formation in recalc

165 n III, and 2 of 10 inhibited inactivation of FXa by antithrombin III.

166 ts of FXa-reactive mAb on AT inactivation of FXa.

167 to FXa and interfere with AT inactivation of FXa.

168 b significantly inhibited AT inactivation of FXa.

169 Induction of FXa activity by ICs containing IgG antibodies to platele

170 Xa also enhanced TFPI-mediated inhibition of FXa approximately 12-fold in the presence of protein S.

171 showed that the rapid rate of inhibition of FXa by the ZPI-PZ complex on procoagulant membrane vesic

172 observed for the PZ-dependent inhibition of FXa by ZPI.

173 d enhancement of TFPI-mediated inhibition of FXa compared with free protein S.

174 FV could enhance TFPI-mediated inhibition of FXa in the presence of protein S, suggesting a functiona

175 These data suggest that inhibition of FXa may be beneficial in prevention and regression of at

176 Pharmacological inhibition of FXa promotes regression of advanced atherosclerotic plaq

177 The fluorescence lifetime of FXa labeled in its active sites with a dansyl fluorophor

178 was replaced with the corresponding loop of FXa.

179 ial cell surface regulates the production of FXa by inhibiting the TF/VIIa complex.

180 agulation and more substantial production of FXa, thrombin, and fibrin as compared with controls.

181 DeltaK3) produced comparable prolongation of FXa-induced coagulation in PS-deficient plasma, but the

182 heparin-mediated enhancement in the rate of FXa inhibition by ZPI was reduced to ~30-fold for ZPI-3A

183 approximately 4-6-fold increases in rates of FXa-catalyzed inactivation of FVIIIa, which paralleled t

184 f ZPI-PZ complex anticoagulant regulation of FXa both before and after incorporation into prothrombin

185 1-41) of FIXa with corresponding residues of FXa renders the FIXa chimera susceptible to inactivation

186 The K(d')s of FXa binding with rFVa (wild-type, C2 mutant, C1 mutant,

187 ine with this, irreversible stabilization of FXa(I16L) with Glu-Gly-Arg-chloromethyl ketone fully res

188 oximine (+)-1j in an asymmetric synthesis of FXa inhibitor F.

189 ing with the anticoagulant function of AT on FXa in some APS patients.

190 -l-serine (C6PS), binds to discrete sites on FXa, FVa, and prothrombin to alter their conformations,

191 sence of calcium, C6PS binds to two sites on FXa, one in the epidermal growth factor-like (EGF) domai

192 n of baboon serum with thrombin, plasmin, or FXa did not show noticeable complement cleavage unless s

193 t cannot be cleaved/activated by thrombin or FXa also enhanced TFPI-mediated inhibition of FXa approx

194 used with factor Xa (FXa) and phospholipids (FXa/phosphatidylcholine-phosphatidylserine [PCPS]) vs LD

195 In hemophilic plasma, FXa(I16L) and FXa(V17A) have prolonged half-lives compar

196 cing a strong burst of thrombin and plasmin, FXa/PCPS infusion did not produce measurable levels of c

197 tification of compound 20 as the most potent FXa inhibitor in this series (IC(50) = 2.4 nM, EC(2xPT)

198 bin to alter their conformations, to promote FXa dimerization (K(d) ~ 14 nM), and to enhance both the

199 tor Xa mutants with zymogen-like properties (FXa(I16L) and FXa(V17A)) circumvent these limitations.

200 ase, a complex consisting of serine protease FXa and cofactor FVa, anchored to anionic phospholipids

201 This was confirmed in purified FXa inhibition assays in which no protein S enhancement

202 VII (TF-FVIIa) via formation of a quaternary FXa-TFPI-TF-FVIIa complex.

203 8, 92, and 128 nM for 5, 20, and 50 nM R165A FXa, respectively).

204 Antagonism of PAR-1 and PAR-2 reduced FXa-induced Ca(2+) release.

205 roquine or fluvastatin significantly reduced FXa-induced and IgG-potentiated Ca(2+) release.

206 ning a mutation in the heparin-binding site (FXa-R240A) was minimally affected by heparin.

207 Importantly, three of six FXa-reactive mAb significantly inhibited AT inactivation

208 sence of anionic membranes as it binds snake-FXa with high affinity in solution.

209 Treatment with a specific FXa inhibitor, hydroxychloroquine or fluvastatin signifi

210 506, Arg-306, and other previously suggested FXa binding sequences, delineate a continuous surface on

211 thrombinase complex on the platelet surface, FXa cleaves ProT at Arg-271, generating the inactive pre

212 n emerges as an atypical serpin that targets FXa and displays unique phospholipid specificity.

213 Our data indicate that TF, FXa, and thrombin differentially contribute to vascular

214 effectively prevented inhibition of FVIIa/TF/FXa and improved clot formation in hemophilia blood and

215 Ia (FVIIa)/tissue factor/Factor Xa (FVIIa/TF/FXa).

216 smon resonance experiments demonstrated that FXa bound TFPI(WT) and TFPI-(DeltaK3) but not the isolat

217 n involving the B domain of FV and show that FXa activation of FV is pivotal for plasma and blood clo

218 ing mouse models of hemophilia, we show that FXa(I16L) has a longer half-life than wild-type FXa and

219 using human or murine analogs, we show that FXa(I16L) is more efficacious than FVIIa, which is used

220 The FXa variants were remarkably effective in mouse injury m

221 In contrast, the FXa-catalyzed hydrolysis of N-alpha-Z-D-Arg-Gly-Arg-pNA.

222 required to understand the structure of the FXa dimer or the FXa-FVa complex.

223 o a membrane, which yielded estimates of the FXa dimerization constant on a membrane as well as the k

224 ng in a "common" pathway at the level of the FXa/FVa (prothrombinase) complex.

225 rstand the structure of the FXa dimer or the FXa-FVa complex.

226 NotD binds specifically to the FXa binding site expressed on factor V (FV) upon activat

227 In the absence of factor Va, the FXa variants are poor enzymes for a range of physiologic

228 de evidence that, contrary to this view, the FXa-specific serpin inhibitor, protein Z-dependent prote

229 hy, and showed an extensive overlap with the FXa contact region highlighting a structural basis for i

230 ented transition from the loose to the tight FXa-TFPI complex, but did not affect formation of the lo

231 for the transition of the loose to the tight FXa-TFPI complex.

232 the fluorescence of fluorescein attached to FXa's active site serine was depolarized in a FXa concen

233 d that some thrombin-reactive Ab may bind to FXa and interfere with AT inactivation of FXa.

234 competitive, reversible and tight binding to FXa (picomolar range).

235 rome (APS) display higher avidity binding to FXa with greater coagulant effects compared to systemic

236 ix of six thrombin-reactive IgG mAb bound to FXa and that the levels of plasma IgG anti-FXa Ab in 38

237 FVa709, FVa699, FVa692, and FVa678 bound to FXa membranes and thrombin-agarose in a manner that was

238 esis that FVa residues 499-505 contribute to FXa binding, we created the FVa loop swap mutant (design

239 Relative to FXa, AT inhibits FIXa with approximately 40-fold slower

240 quence alignments indicated that, similar to FXa, residue 36 is a Glu in both mouse and bovine FIXa a

241 rypsin-like serine proteases (thrombin, tPA, FXa, plasmin, plasma kallikrein, trypsin, FVIIa).

242 (I16L) has a longer half-life than wild-type FXa and does not cause excessive activation of coagulati

243 tivation, paradoxically allowing uninhibited FXa to persist in plasma.

244 showed reduced onset of atherosclerosis upon FXa inhibition, the effect on pre-existing plaques has n

245 uding that of the most zymogen-like variant (FXa-I16T), was greatly enhanced when bound to FVa membra

246 that a novel zymogen-like factor Xa variant (FXa-I16L) was effective in correcting the coagulation de

247 In vitro, FXa stably associated with TF-FVIIa activates FVIII, but

248 verse, 0.30 +/- 0.05 and 0.19 +/- 0.04, when FXa/FVa is 1:4, with an increasing FXa and substrate con

249 ations > 5 Km, the KSIE is 1.6 +/- 0.3, when FXa is in a 1:1 ratio with FVa but becomes increasingly

250 (7) m(-1) s(-1)) was decreased ~10-fold when FXa was bound to FVa in prothrombinase and a further ~3-

251 edominance of the meizothrombin pathway when FXa is well-saturated with the prothrombin complex.

252 ated PAR activation and investigated whether FXa reactive IgG from patients with APS or SLE/APS- alte

253 ived monoclonal IgG antiphospholipid Ab with FXa and the presence of IgG anti-FXa Ab in APS patients

254 Thrombin combined with FXa/FVIIa enhanced infection, suggesting that PAR1 and P

255 The BR competes with FXa for binding to FV(a), and limited proteolysis of the

256 rom ZPI once ZPI forms a stable complex with FXa, and kinetic analyses confirmed that PZ acted cataly

257 main enables TFPI to interact optimally with FXa on a phospholipid membrane.

258 utants exhibited near normal reactivity with FXa and FXIa in the absence of cofactors and in the pres

259 in when the variant was fully saturated with FXa membranes.

260 or myocardial infarction with DTIs than with FXa inhibitors.

261 a novel biomarker to stratify treatment with FXa inhibitors in these patients.

262 reversible inhibitor of activated factor X (FXa) and also inhibits the FVIIa-TF complex.

263 idering that activated coagulation factor X (FXa) is homologous to thrombin in the catalytic domains

264 ociation with the enzyme activated factor X (FXa) to form the prothrombinase complex is a pivotal ini

265 inhibitor that inhibits activated factor X (FXa) via a slow-tight binding mechanism and tissue facto

266 is a well-characterized activated factor X (FXa)-dependent inhibitor of TF-initiated coagulation pro

267 bound to the activated coagulation factor X (FXa).

268 mbin and the activated coagulation factor X (FXa).

269 rating the inhibition of activated factor X (FXa).

270 inhibit the activity of activated factor X (FXa); however, neither inhibitor exhibits any reactivity

271 e show that activated coagulation factors X (FXa) or VII (FVIIa) directly affect HSV1 infection of hu

272 f the serpin with factors IXa (FIXa) and Xa (FXa), thereby improving the rate of reactions by 300- to

273 logous to coagulation factors V (FV) and Xa (FXa).

274 lly pliant variant of coagulation factor Xa (FXa(I16L)) rendered partially inactive by a defect in th

275 Here we found that factor Xa (FXa) activated PAR1 at canonical Arg41 similar to thromb

276 e, plasma concentration, and anti-Factor Xa (FXa) activity and compared efficacy and safety outcomes

277 in the induction of TF-dependent factor Xa (FXa) activity by IgG-containing ICs by THP-1 monocytic c

278 er of highly selective and potent factor Xa (FXa) and FIXa inhibitors were identified by simple switc

279 a, C5b-9) in baboons infused with factor Xa (FXa) and phospholipids (FXa/phosphatidylcholine-phosphat

280 icoagulant that binds coagulation factor Xa (FXa) and zymogen FX, with formation of a quaternary tiss

281 Current thought holds that factor Xa (FXa) bound in the prothrombinase complex is resistant to

282 S (PS) enhances the inhibition of factor Xa (FXa) by tissue factor pathway inhibitor-alpha (TFPI-alph

283 bit both TF-factor VIIa-dependent factor Xa (FXa) generation and free FXa.

284 Factor Xa (FXa) has a prominent role in amplifying both inflammatio

285 r snake, Notechis scutatus, and a factor Xa (FXa) homolog.

286 The molecular mechanism of factor Xa (FXa) inhibition by Alboserpin, the major salivary gland

287 ct thrombin inhibitors (DTIs) and factor Xa (FXa) inhibitors, are emerging alternatives for prophylax

288 osphatidylserine (C6PS) to bovine factor Xa (FXa) leads to Ca2+-dependent dimerization in solution.

289 Direct inhibitors of coagulation factor Xa (FXa) or thrombin are promising oral anticoagulants that

290 membrane-dependent interaction of factor Xa (FXa) with factor Va (FVa) forms prothrombinase and drive

291 t key clotting proteases, such as factor Xa (FXa), can promote atherosclerosis, presumably mediated t

292 t isotope effects (KSIEs) for the factor Xa (FXa)-catalyzed activation of prothrombin in the presence

293 nt anticoagulant role through the factor Xa (FXa)-dependent inhibition of tissue factor/factor VIIa.

294 ical process culminating with the factor Xa (FXa)-mediated conversion of the prothrombin (ProT) zymog

295 t to an active cofactor (FVa) for factor Xa (FXa).

296 se inhibitor (ZPI) inhibition of factors Xa (FXa) and XIa (FXIa) by a template mechanism.

297 t regulator of blood coagulation factors Xa (FXa) and XIa.

298 ial assembly of a membrane-associated PZ-ZPI-FXa Michaelis complex (K(M) 53+/-5 nM) followed by conve

299 5 nM) followed by conversion to a stable ZPI-FXa complex (k(lim) 1.2+/-0.1 s(-1)).

300 The ZPI-FXa complex was only transiently stable and dissociated