Inhibition of Bovine Factor VIII and Ristocetin Plus Human Factor VIII Induced Platelet Agglutination by Small Peptides

1975 ◽  
Author(s):  
D. E. Macfarlane
Keyword(s):  
Factor Viii ◽  
Human Factor ◽  
Human Platelets ◽  
Small Peptides ◽  
Platelet Surface ◽  
Muramyl Peptide ◽  
Human Factor Viii ◽  
Peptide Precursor ◽  
Von Willebrand ◽  
Bovine Factor

The antibiotic ristocetin induces platelet agglutination in the presence of human factor VIII. A similar agglutination is induced by bovine factor VIII without ristocetin. This antibiotic binds C-terminal D-alanine peptides including the nucleotide-N-acetyl-muramyl-peptide precursor of bacterial cell walls. The effect of several peptides on the agglutination of formalin fixed washed human platelets was investigated. At 1.25 mM acetyl-glycyl-D-alanine (AGDA) and diacetyl-L-lysine-D-alanine-D-alanine (ALAA) increased the amount of ristocetin required for agglutination in the presence of purified human factor VIII; both these peptides bind to ristocetin (Bichochem. J. 124, 845). Glycyl-L-alanine (GLA) glycyl-D-alanine (GDA), acetyl-glycyl-L-alanine (AGLA) were inactive. AGLA (0.25 mM) and AGDA (1.25 mM) inhibited purified bovine factor VIII induced agglutination, ALAA, GLA and GDA (3.2 mM) were inactive.These results suggest that ristocetin acts in part by binding to peptides on the platelet surface, and that bovine VIII combines to the same site but has a different specificity. Suitable small peptides may be able to induce a von Willebrand like state for therapeutic purposes.(Dr. Kirby, Temple University provided the purified factor VIII’s and Prof. Perkins, Liverpool University provided ALAA; supported by N. I. H. HL 14217.)

scholarly journals The effect of plasma von Willebrand factor on the binding of human factor VIII to thrombin-activated human platelets.

1991 ◽  
Vol 266 (27) ◽  
pp. 17815-17820
Author(s):  
M. Nesheim ◽  
D.D. Pittman ◽  
A.R. Giles ◽  
D.N. Fass ◽  
J.H. Wang ◽  
...  
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Human Factor ◽  
Human Platelets ◽  
Human Factor Viii ◽  
Von Willebrand ◽  
Willebrand Factor

Evans Blue: A Specific Inhibitor of Factor VIII-Induced Platelet Agglutination

1975 ◽  
Vol 34 (03) ◽  
pp. 770-779 ◽  
Author(s):  
E. P Kirby
Keyword(s):  
Factor Viii ◽  
Evans Blue ◽  
Human Factor ◽  
Specific Inhibitor ◽  
Platelet Surface ◽  
Low Concentrations ◽  
Human Factor Viii ◽  
Bovine Factor

SummaryLow concentrations of Evans Blue ( < 1 μM) inhibit the agglutination of formalin-treated platelets by bovine Factor VIII or by human Factor VIII in the presence of the antibiotic ristocetin. Evans Blue is a specific inhibitor of this reaction and acts by inhibiting the binding of Factor VIII to the platelet surface.

Impaired Prothrombin Consumption in Bernard-Soulier Syndrome Is Corrected In Vitro by Human Factor VIII

1997 ◽  
Vol 77 (02) ◽  
pp. 383-386 ◽  
Author(s):  
S Bellucci ◽  
J P Girma ◽  
M Lozano ◽  
D Meyer ◽  
J P Caen
Keyword(s):  
Factor Viii ◽  
Human Factor ◽  
Platelet Membrane ◽  
Giant Platelets ◽  
Prolonged Bleeding Time ◽  
Human Factor Viii ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Bernard Soulier Syndrome

SummaryThe Bernard-Soulier syndrome (BSS) is characterized by thrombocytopenia with giant platelets, a prolonged bleeding time with defective platelet adhesion to the subendothelium related to a defect in platelet membrane glycoprotein lb (GPIb) and a decreased prothrombin consumption. The mechanism of the latter abnormality remains unknown. In this study, we showed that this defect was corrected by the addition of purified human factor VIII (FVIII) to blood from four patients with BSS. The correction of prothrombin consumption was almost complete at concentrations between 1.5 and 3 IU/ml of FVIII procoagulant activity (VIII.'C) and partially abolished by a monoclonal antibody which neutralizes VIII:C. This correction was specific for FVIII and was not observed after addition of purified human FIX. It was obtained, in the same magnitude range, with FVIII complexed to von Willebrand factor (vWF) but not with free vWF. These data provide a new insight into the knowledge of the physiological interaction between the platelet membrane and the vWF-FVIII complex facilitating plasma coagulation activation and may lead to helpful therapeutic advances.

scholarly journals Factor VIII/von Willebrand factor in subendothelium mediates platelet adhesion

Blood ◽  
1985 ◽  
Vol 65 (4) ◽  
pp. 823-831 ◽  
Author(s):  
VT Turitto ◽  
HJ Weiss ◽  
TS Zimmerman ◽  
II Sussman
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Vessel Wall ◽  
Platelet Adhesion ◽  
Human Factor ◽  
Rabbit Aorta ◽  
Human Factor Viii ◽  
Plasma Factor ◽  
Von Willebrand ◽  
Willebrand Factor

The present studies were undertaken to determine whether factor VIII/von Willebrand factor (vWF) present in the vessel wall (in addition to that in plasma) may mediate the attachment of platelets to subendothelium. Subendothelium from everted rabbit aorta was exposed to human citrated blood flowing through an annular perfusion chamber at 40 mL/min (wall shear rate of 2,600 s-1 for five minutes). The vessel segments were incubated at 37 degrees C for one hour with various dilutions of either goat-anti-rabbit factor VIII/vWF serum or an IgG fraction prepared from the serum. Control segments were incubated with serum or IgG from a nonimmunized goat. Values of platelet contact (C), platelet adhesion (C + S), and thrombus formation (T) on the subendothelium were evaluated by a morphometric technique. Compared with vessels incubated with fractions prepared from a normal goat, a significant decrease in platelet adhesion (C + S), ranging from 45% to 65%, was observed on vessels incubated with various dilutions (1:5 to 1:50) of either serum or IgG fractions of goat-anti-rabbit factor VIII/vWF. A similar decrease in platelet adhesion was observed with vessels incubated with an F(ab')2 fragment against rabbit factor VIII/vWF prepared in the goat. When goat-anti-rabbit factor VIII/vWF IgG was added to rabbit blood (1:75 dilution), platelet adhesion was reduced to the same extent (65%) on normal rabbit vessels and on vessels pre-incubated with goat-anti-rabbit factor VIII/vWF. Immunofluorescence studies revealed the presence of rabbit factor VIII/vWF in the subendothelium of rabbit aorta and the continued binding of the goat-anti-factor VIII/vWF antibodies on subendothelium during the perfusion studies. No uptake of human factor VIII/vWF on the rabbit subendothelium was observed by this immunologic technique; human factor VIII/vWF was found to be entirely associated with the attached human platelets. Thus, factor VIII/vWF in the vessel wall may mediate platelet attachment to subendothelium in a manner similar to that of plasma factor VIII/vWF.

Crossed Concanavalin A Affinoimmunoelectrophoresis Of Factor VIII - Related Antigen In Whole Plasma

1981 ◽  
Author(s):  
J S Krauss ◽  
M Sheard
Keyword(s):  
Factor Viii ◽  
Concanavalin A ◽  
Human Factor ◽  
Von Willebrand Disease ◽  
Con A ◽  
Factor Viii Related Antigen ◽  
Crossed Immunoelectrophoresis ◽  
Human Factor Viii ◽  
Normal Human ◽  
Von Willebrand

Normal human factor VIII is precipitated by the lectin concanavalin A (con A). In order to study this interaction pooled normal plasma has been subjected to crossed affinoimmunoelectrophoresis with con A in the first dimension and commercial antiserum to factor VIII in the second dimension. Both decreased anodal migration and decreased precipitin height of the factor VIII - related antigen (FVIIIR:ag) confirmed the precipation of FVIIIR:ag by con A.This technique, performed in conjunction with crossed immunoelectrophoresis (CIEP) of FVIIIR:ag, should prove useful in the analysis of von Willebrand disease (vWd) variants whose FVIIIR:ag has decreased carbonhydrate and, therefore, is poorly precipitated by con A.

scholarly journals von Willebrand Factor Activity in Plasmin Digests of Factor VIII

1977 ◽  
Author(s):  
J. A. Guisasola ◽  
C. Cockburn ◽  
R. M. Hardisty
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Human Factor ◽  
Factor Activity ◽  
Group Iii ◽  
Molecular Weights ◽  
Human Factor Viii ◽  
Group Ii ◽  
Von Willebrand ◽  
Willebrand Factor

Purified human factor VIII was incubated for up to 24 hours with plasmin, and the activity of the breakdown products studied at intervals. Factor VIII coagulant activity was lost within the first hour, but von Willebrand factor activity (FVIIIR:WF) was retained for two hours, and then declined slowly during the subsequent incubation. Analysis of the 24-hour breakdown products by immuno-electrophoresis, sepharose 4B chromatography and SDS Polyacrylamide electrophoresis revealed three main groups of fragments recognised by rabbit anti-human factor VIII anti-serum, and having molecular weights in the following ranges: Group 1 300,000=500,000; Group II, 150–200,000; Group III, 100,000. FVIIIR:WF activity, which was found only in Group II, appeared to be associated with glycopeptide(s) of up to 155,000 daltons.

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