scholarly journals A factor VIII-derived peptide enables von Willebrand factor (VWF)-binding of artificial platelet nanoconstructs without interfering with VWF-adhesion of natural platelets

Nanoscale ◽  
2014 ◽  
Vol 6 (9) ◽  
pp. 4765-4773 ◽  
Author(s):  
Hassan Haji-Valizadeh ◽  
Christa L. Modery-Pawlowski ◽  
Anirban Sen Gupta
Keyword(s):  
Platelet Aggregation ◽  
Factor Viii ◽  
Von Willebrand Factor ◽  
Mimetic Peptides ◽  
Binding Peptides ◽  
Von Willebrand ◽  
Willebrand Factor

Co-decoration of liposomal nanoconstructs with FVIII-derived VWF-binding-peptides (VBP) and active platelet-clustering fibrinogen-mimetic-peptides (FMP) allows platelet-mimetic VWF-adhesion and platelet aggregation.

scholarly journals Characterization of 25 monoclonal antibodies to factor VIII-von Willebrand factor: relationship between ristocetin-induced platelet aggregation and platelet adherence to subendothelium

Blood ◽  
1984 ◽  
Vol 63 (6) ◽  
pp. 1408-1415 ◽  
Author(s):  
HV Stel ◽  
KS Sakariassen ◽  
BJ Scholte ◽  
EC Veerman ◽  
TH van der Kwast ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Platelet Aggregation ◽  
Factor Viii ◽  
Von Willebrand Factor ◽  
Primary Hemostasis ◽  
Platelet Adherence ◽  
Physiologic Mechanism ◽  
Von Willebrand ◽  
Induced Aggregation ◽  
Willebrand Factor

Abstract We have studied the role of factor VIII-von Willebrand factor (FVIII- vWF) in both platelet adherence to subendothelium and ristocetin- induced platelet aggregation using monoclonal antibodies to human FVIII- vWF. Twenty-five monoclonal antibodies were obtained, two of which were directed to the factor VIII moiety of FVIII-vWF; one of these two completely inhibited the procoagulant activity (FVIII:C). The remaining 23 monoclonal antibodies were directed to the von Willebrand factor moiety of FVIII-vWF. The ability of the latter monoclonal antibodies to inhibit platelet adherence to arterial subendothelium was investigated with a perfusion model. According to the number of platelets adhering to the subendothelium, three groups of monoclonal antibodies could be discerned: (A) antibodies not affecting platelet adherence; (B) antibodies that inhibited platelet adherence to the level as observed when von Willebrand's disease plasma was tested; and (C) antibodies that completely inhibited both platelet adherence to subendothelium and ristocetin-induced platelet aggregation. The two antibodies present in group C competed for the same or closely related epitope(s) present on FVIII-vWF. These results demonstrate that a domain is present on the FVIII-vWF molecule that is associated both with ristocetin-induced aggregation and with the ability of FVIII-vWF to support platelet adherence to the subendothelium. Based on these observations, it is concluded that ristocetin-induced binding of FVIII-vWF to platelets reflects, at least in part, a physiologic mechanism regulating the function of FVIII-vWF in primary hemostasis.

scholarly journals Specificity of Factor VIII Inhibitor for Procoagulant Activity

1977 ◽  
Author(s):  
H. Yang ◽  
M. Kuzur
Keyword(s):  
Platelet Aggregation ◽  
Factor Viii ◽  
Von Willebrand Factor ◽  
Hemophilia A ◽  
Test Sample ◽  
Factor Viii Inhibitor ◽  
Viii Inhibitor ◽  
The Mean ◽  
Von Willebrand ◽  
Willebrand Factor

Nine hemophilia A patients with an inhibitor to factor VIII procoagulant and eight without an inhibitor were studied for the presence of an inhibitor to von Willebrand factor (vWf). After a 2 hour incubation at 37°C, test plasma, normal pooled plasma and test plasma mixed with normal pooled plasma were assayed for vWf in the quantitative ristocetin-induced platelet aggregation system. The mean vWf was 1.31±.59 unit/ml in the non-inhibitor group and 1.46±.52 in the inhibitor group. In the non-inhibitor group the predicted vWf (summation of the test sample and normal plasma) was 1.38±.37 unit/ml, whereas the actual vWf of the mixture was 1.23±.35. In the inhibitor group the predicted vWf was 1.46±.33 unit/ml, whereas the actual vWf of the mixture was 1.44±.40. The results in the two groups were not significantly different. Neither group had inhibitory activity for vWf. The factor VIII inhibitor is highly specific for the procoagulant part of the factor VIII complex.

scholarly journals Characterization of 25 monoclonal antibodies to factor VIII-von Willebrand factor: relationship between ristocetin-induced platelet aggregation and platelet adherence to subendothelium

Blood ◽  
1984 ◽  
Vol 63 (6) ◽  
pp. 1408-1415 ◽  
Author(s):  
HV Stel ◽  
KS Sakariassen ◽  
BJ Scholte ◽  
EC Veerman ◽  
TH van der Kwast ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Platelet Aggregation ◽  
Factor Viii ◽  
Von Willebrand Factor ◽  
Primary Hemostasis ◽  
Platelet Adherence ◽  
Physiologic Mechanism ◽  
Von Willebrand ◽  
Induced Aggregation ◽  
Willebrand Factor

We have studied the role of factor VIII-von Willebrand factor (FVIII- vWF) in both platelet adherence to subendothelium and ristocetin- induced platelet aggregation using monoclonal antibodies to human FVIII- vWF. Twenty-five monoclonal antibodies were obtained, two of which were directed to the factor VIII moiety of FVIII-vWF; one of these two completely inhibited the procoagulant activity (FVIII:C). The remaining 23 monoclonal antibodies were directed to the von Willebrand factor moiety of FVIII-vWF. The ability of the latter monoclonal antibodies to inhibit platelet adherence to arterial subendothelium was investigated with a perfusion model. According to the number of platelets adhering to the subendothelium, three groups of monoclonal antibodies could be discerned: (A) antibodies not affecting platelet adherence; (B) antibodies that inhibited platelet adherence to the level as observed when von Willebrand's disease plasma was tested; and (C) antibodies that completely inhibited both platelet adherence to subendothelium and ristocetin-induced platelet aggregation. The two antibodies present in group C competed for the same or closely related epitope(s) present on FVIII-vWF. These results demonstrate that a domain is present on the FVIII-vWF molecule that is associated both with ristocetin-induced aggregation and with the ability of FVIII-vWF to support platelet adherence to the subendothelium. Based on these observations, it is concluded that ristocetin-induced binding of FVIII-vWF to platelets reflects, at least in part, a physiologic mechanism regulating the function of FVIII-vWF in primary hemostasis.

scholarly journals Factor VIII/von Willebrand factor binding to von Willebrand's disease platelets

Blood ◽  
1982 ◽  
Vol 60 (2) ◽  
pp. 328-332 ◽  
Author(s):  
HR Gralnick ◽  
SB Williams ◽  
BC Shafer ◽  
L Corash
Keyword(s):  
Platelet Aggregation ◽  
Factor Viii ◽  
Von Willebrand Factor ◽  
Von Willebrand's Disease ◽  
Platelet Surface ◽  
Platelet Receptors ◽  
Von Willebrand’S Disease ◽  
Binding Data ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract A form of von Willebrand's disease has been described with enhanced ristocetin-induced platelet aggregation and anodal migration of the factor VIII/von Willebrand factor protein (type IIb). We studied two families with this form of von Willebrand's disease and macrothrombocytopenia. We have found that these platelets bind more of the normal and intermediate-sized multimers of the factor VIII/von Willebrand factor than normal platelets. Analysis of the binding data show an increased affinity of these vWd platelets for the factor VIII/von Willebrand factor. These findings are consistent with an increased number of platelet receptors, which, either by their native topography or migration on the platelet surface, bind factor VIII/von Willebrand factor protein with greater affinity than normal platelets, platelets of other vWd patients, and large platelets of other etiologies.

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