Factor VIII In Vessel Wall Influences Platelet Interaction With Subendothelium

1981 ◽  
Author(s):  
V Turitto ◽  
H Weiss ◽  
I Sussman ◽  
T Zimmerman
Keyword(s):  
Factor Viii ◽  
Vessel Wall ◽  
Thrombus Formation ◽  
Balloon Catheter ◽  
Rabbit Aorta ◽  
Normal Serum ◽  
Endothelial Lining ◽  
Vascular Surface ◽  
Catheter Technique ◽  
Plasma Factor

Immunological techniques have demonstrated the presence of factor VIII:AGN in both the endothelium and deeper layers of vessel wall. Since plasma factor VIII:VWF is known to mediate platelet adhesion to subendothelium, we investigated the influence of vessel wall factor VIII on platelet interaction with the vascular surface. Everted vessel segments (14 mm in length) from rabbit aorta, denuded of their endothelial lining by a balloon catheter technique, were incubated for 1 hr at 37°C in 1ml of either 0.2M Tris buffer (B), normal goat serum diluted 1/5 with B or goat serum containing an antibody to rabbit factor VIII:VWF diluted 1/5, 1/20 or 1/100 with B. The segments were exposed in an annular chamber to citrated huipn blood, flowing at 40ml/min (wall shear rate of 2600 sec-1 ) for 5 min. The percentage of subendothelial surface covered with adherent platelets (A) or platelet thrombi greater than 5μm in height (T) were determined morphometrically. Values of A were significantly decreased on vessels treated with serum containing antibody diluted 1/5 (A=30.4±5.9, p<0.0l) or 1/20 (A=31.7±5.0, p<0.0l) but not 1/100 (A=37.7±7.4, p=NS) compared to vessels incubated with either B(A=53.8±5.l) or normal serum (A=58.0±7.9). Thrombus formation (T) was not significantly decreased by treatment of the vessel wall with serum containing antibody. Similar results were obtained when the IgG fractions of serum were used instead of whole serum.Thus, it appears that factor VIII:AGN in the vessel wall may be important in the initial platelet events involved in hemostasis. The relative importance of vessel wall factor VIII versus that present in the plasma requires further study.

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.

Effect Of Selective Inhibition Of Platelet Thromboxane On Platelet-Vessel Wall Interaction In Vivo

1981 ◽  
Author(s):  
Y C Chen ◽  
K K Wu ◽  
E R Hall ◽  
D L Venton ◽  
G C Le Breton
Keyword(s):  
Vessel Wall ◽  
Platelet Reactivity ◽  
Thrombus Formation ◽  
Balloon Catheter ◽  
Specific Inhibitor ◽  
Constant Infusion ◽  
Catheter Technique ◽  
Platelet Thrombus ◽  
Platelet Accumulation

It is well recognized that thromboxane A2(TXA2) plays an important role in platelet reactivity. To determine the role of TXA2 in platelet-vessel wall (P-V) interaction, the effect of 1-benzylimidazole (1-BI), a specific inhibitor of thromboxane synthetase, and 13-azaprostanoic acid (APA), a TXA2 antagonist, on platelet thrombus formation was evaluated in vivo in NZW male rabbits using the autologous indium-111 (111In) labeled platelet technique. Rabbits were treated with intravenous 1-BI or APA or vehicles. After injection of autologous 111In-platelets, de-endothelialization of the abdominal aorta was created by a balloon catheter technique. At 3 hrs, blood samples were obtained and the animals were sacrificed. The aortae were removed and the injured and uninjured segments were dissected. Radioactivity counts and dry weight of the tissues and blood were determined. The vascular radioactivity counts were converted to platelet numbers by using a standard linear calibration curve. As small numbers of platelets adhered to normal vessel wall nonspecifically, this number was subtracted to obtain specific platelet accumulation at the injured sites. 1-BI at 10mg/kg reduced the specific platelet accumulation significantly (n=5, 12.3±S.D.I.5×106 pl/gm tissue; p<0.01) when compared with the controls (n=10, 33.0±5.1×106 pl/gm tissue). Platelet accumulation was further reduced by increasing the dosage to 30mg/kg. By contrast, APA injection (10mg/kg) had no significant effect. However, when APA was given by constant infusion at 250μg/kg/min 1 hr prior to injury, the APA-treated animals had an 80% reduction of platelet accumulation relative to controls. These findings indicate that TXA2 plays an important role in P-V interaction and specific inhibition of TXA2 appears to be efficacious in eliminating platelet thrombus formation.

THROMBOGENICITY OF THE VESSEL WALL AFTER SINGLE AND REPEATED INJURY

1987 ◽  
Author(s):  
B Pasche ◽  
J Swedenborg ◽  
A Ljungqvist
Keyword(s):  
Endothelial Cells ◽  
Enzymatic Activity ◽  
Vessel Wall ◽  
Morphological Changes ◽  
Balloon Catheter ◽  
Internal Elastic Lamina ◽  
Endothelial Lining ◽  
Vascular Surface ◽  
Repeated Injury

Departments of Experimental Surgery and Pathology, Karolinska HospitalStockholm, Sweden Injury to the endothelial lining of the vessel wall gives rise to increased thrombogenicity but fibrin formation is only seen after repeated injuryThe purpose of the present study was to simultaneously study the appearance of thrombin enzymatic activity and morphological changes on the injured vascular surface after primary and repeated injury. Endothelial injury was caused by balloon catheter in rabbits. The animals were sacrificed and the aorta was excised, inverted and mounted on a plastic rod. Thrombin enzymatic activity was measured on the surface by exposing it to either a chromo-genic substrate (thrombin$) or fibrinogen (thrombinp). In the latter case generation of fibrinopeptide (FPA) was measured. Standard light microscopic procedures were also performed After injury no endothelial cells were seen. Thickening of the internal elastic lamina and accumulation of granulocytes and platelets was also noted. Thrombin^ and thrombinp was detected on the surface. One week after injury the vessel wall had healed but the endothelial . cells were metachromatic and had numerable mitoses. No thrombin activity exceeding the control was seen. After repeated injury thrombins and thrombinp were again demonstrated but the fraction constituting thrombinp was larger than after primary injury. Microscopy at this time showed severe changes including vacuolisationThe capacity of the surface to inhibit thrombin in vitro was also studied and it was found that this capacity was lower after repeated injury particularly in the case of thrombinpIt is concluded that injury of the endothelium gives rise to appearance of thrombin enzymatic activity. After repeated injury proportionally more thrombinp is found, which may explain why fibrinogen is more easily demonstrated on the surface after repeated injury

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

Abstract 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.

Antithrombotic Effects of Recombinant Hirudin in Experimental Angioplasty and Intravascular Thrombolysis

1990 ◽  
Vol 63 (01) ◽  
pp. 044-047 ◽  
Author(s):  
Brigitte Kaiser ◽  
Antje Simon ◽  
Fritz Markwardt
Keyword(s):  
Femoral Artery ◽  
Subcutaneous Injection ◽  
Vessel Wall ◽  
Thrombus Formation ◽  
Balloon Catheter ◽  
Endothelial Damage ◽  
Recombinant Hirudin ◽  
Arterial Thrombus ◽  
Short Period ◽  
Antithrombotic Effects

SummaryThe effect of recombinant desulphatohirudin CGP 39393 (rH) on arterial thrombus formation and especially on thrombotic reocclusion after experimental angioplasty as well as after thrombolysis was investigated in rabbits. In the femoral artery thrombi were induced after endothelial damage of the vessel wall by a balloon catheter and following stasis. After removing the thrombus by angioplasty or after lysing it by streptokinase reocclusion of the artery was observed within a relatively short period of time. Subcutaneous injection of rH reduced the incidence of both primary thrombus formation and reocclusion in dependence on the dose administered. After a dose of rH of 2 mg/kg s.c. arterial thrombus formation was completely prevented and after administering 4 mg/kg s.c. thrombotic reocclusion did also not occur. Comparative studies with heparin showed that similar antithrombotic effects were only achieved at doses of 12 mg heparin/kg s.c. The results obtained suggest a clear potential of rH for prevention of thrombotic reocclusion in clinical states.

scholarly journals Antibodies as a Cause for Platelet Functional Defects

1977 ◽  
Author(s):  
J. P. Caen ◽  
S. Levy-Toledano ◽  
C. Tobelem ◽  
H. Michel ◽  
A. T. Nurden ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Factor Viii ◽  
Human Platelet ◽  
Thrombus Formation ◽  
Rabbit Aorta ◽  
Human Platelets ◽  
Platelet Membranes ◽  
Normal Human ◽  
Functional Defects ◽  
Bovine Factor

The Luc. antibody occurring in a polytransfused thrombasthenic patient is an IgG which agglutinates all human platelets except thrombasthenic ones. At sub-agglutinating doses, ADP, Adrenaline, Collagen, Thrombin and arachidonic acid-induced aggregations but not ristocetin and bovine factor VIII mediated platelet aggregations are inhibited. It does not modify ADP binding to normal human platelet membranes. The antibody strongly reduced thrombus formation on rabbit aorta subendothelium. Its activity is consumed after incubation with normal human platelet membranes but not with thrombasthenic ones. It inhibits thromboxane formation with all inducers but not with arachidonic acid and PGG2. This antibody reacts with a component present on human platelet membranes 120.000 MW.The Por. antibody occurring in a polytransfused Bernard-Soulier patient is an IgG which agglutinates all human platelets except those of Bernard-Soulier and thrombasthenia. The activity is consumed after incubation with normal and thrombasthenic platelet membranes but not with platelet membranes of Bernard-Soulier patients. At sub-agglutinating doses only ristocetin, bovine factor VIII aggregation and adhesion of human platelets to rabbit aorta subendothelium are inhibited. Purified neuraminidase, chymotrypsin or trypsin destroy the reaction of normal platelets with this antibody. This IgG reacts with a component of human platelet membrane 155.000 MW.

Thrombin Activity Appearing on the Vessel Wall After Trauma

1985 ◽  
Vol 54 (04) ◽  
pp. 773-775 ◽  
Author(s):  
M Dryjski ◽  
P Olsson ◽  
J Swedenborg
Keyword(s):  
Soft Tissue ◽  
Vessel Wall ◽  
Balloon Catheter ◽  
Endothelial Injury ◽  
Amidolytic Activity ◽  
Soft Tissue Trauma ◽  
Vascular Surface ◽  
Thrombin Activity ◽  
Tissue Trauma ◽  
Damaged Vessel

SummaryThrombin activity was assayed on the aortic surface of rabbits after soft tissue trauma or endothelial injury caused by a balloon catheter. The animals were sacrificed by exsanguination 20 minutes or 3 hours after either type of trauma. Thrombin amidolytic activity on the luminal surface of the aorta was measured by exposing it to a synthetic chromogenic substrate.Thrombin activity appeared on the aortic endothelium 3 hours but not 20 minutes after soft tissue trauma. Heparin prevented the appearance of thrombin activity completely only if given just before the trauma. After endothelial injury, thrombin activity appeared on the vascular surface after 3 hours but not after 20 minutes.Thrombin activity appearing on the endothelium after soft tissue trauma may explain posttraumatic thrombotic events. The thrombin activity could, however, also be directed towards activation of protein C in which case an anticoagulant effect is obtained. Thrombin appearing after endothelial injury may enhance reactivity on the damaged vessel wall.

Fibrin-Rich and Platelet-Rich Thrombus Formation on Neointima: Recombinant Tissue Factor Pathway Inhibitor Prevents Fibrin Formation and Neointimal Development following Repeated Balloon Injury of Rabbit Aorta

1998 ◽  
Vol 80 (09) ◽  
pp. 506-511 ◽  
Author(s):  
Yujiro Asada ◽  
Seiichiro Hara ◽  
Atsushi Tsuneyoshi ◽  
Kinta Hatakeyama ◽  
Atsushi Kisanuki ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Balloon Angioplasty ◽  
Tissue Factor Pathway Inhibitor ◽  
Thrombus Formation ◽  
Balloon Catheter ◽  
Rabbit Aorta ◽  
Severe Injury ◽  
Balloon Injury ◽  
Injury Group ◽  
Tissue Factor Pathway

SummaryThrombus formation and neointimal growth are the critical events in restenosis after balloon angioplasty. However, the responses of diseased vessels to injuries caused by balloon angioplasty have not been well examined. We investigated the thrombus formation and neointimal development following the balloon injury to the previously induced neointima in the rabbit aorta and the effects of recombinant tissue factor pathway inhibitor (rTFPI) on these responses. Rabbit thoracic aortas were subjected to injury with a Fogarty 4F balloon catheter at 1.75 atm (first injury), and 4 weeks later the same vessels were subjected to the second injury with a Swan-Ganz 5F balloon catheter at 1.4 atm (mild-injury group) or 1.8 atm (severe-injury group), and immediately after that a retrograde bolus injection of rTFPI (100 μg/kg body weight) or saline was performed into the injured segments via the central tube of the Swan-Ganz catheter. Twenty minutes after the second injury, the injured surfaces were covered with platelet-rich thrombi in the mild-injury group and with fibrin-rich thrombi in the severe-injury group. Damaged intimal smooth muscle cells, which were immunohistochemically positive for tissue factor (TF), were observed beneath the fibrin-rich thrombi. The neointima 4 weeks after the second injury was significantly thicker in the severe-injury group than in the mild-injury group. The bolus infusion of rTFPI markedly inhibited fibrin formation on the injured surfaces, and significantly reduced the neointimal development in the severe-injury group at 4 weeks after the second injury. These results indicate that TF-dependent coagulation pathway is primarily responsible for fibrin-rich thrombus formation and may play an important role in neointimal development following the balloon injury to the rabbit aortic neointima. Additionally the bolus administration of rTFPI to the injured vessels could prevent mural thrombus formation and neointimal growth after balloon angioplasty.

Relationship between Factor VIII and von Willebrand’s Factor in Plasma and Serum

1975 ◽  
Author(s):  
J. Koutts ◽  
N. Gude ◽  
B. Firkin
Keyword(s):  
Factor Viii ◽  
Dynamic Equilibrium ◽  
Normal Serum ◽  
Normal Plasma ◽  
Plasma Factor ◽  
Factor Viii Antigen ◽  
Von Willebrand’S Factor ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Subsequent Addition

A monospecific precipitating antibody with no factor VIII procoagulant neutralisation activity, but which inhibited normal ristocetin induced platelet aggregation was produced. The antibody was insolubilised on Sepharose beads. On mixing with normal plasma, factor VIII procoagulant activity (VIII C), von Willebrand factor (vWf) and factor VIII antigen (VIII Ag) were removed in equal proportions. The VIII C lost from plasma was detectable on the Sepharose beads. This activity was removed after treatment of these beads with high molarity solution. Subsequent addition of plasma resulted in a high transfer of VIII C from the plasma to the Sepharose beads without accompanying vWf and VIII Ag. Similar experiments, initially mixing with normal serum showed equivalent binding of vWf and VIII Ag. No independent attachment of VIII C to these beads was demonstrated when they were treated with high molarity solutions and normal plasma then added.It is suggested that VIII C and vWf exist in plasma as separate but attached molecules in a dynamic equilibrium. In serum, vWf has lost its ability to attach VIII C.

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