The Role of Factor VIII-von Willebrand Factor in Adhesion of Platelets to the Vessel Wall

Von Willebrand factor (VWF) is a multimeric plasma glycoprotein that plays a central role in the initiation of blood coagulation. Through interactions between its specific functional domains, the vascular wall, coagulation factor VIII, and platelet receptors, VWF maintains hemostasis by binding to platelets and delivering factor VIII to the sites of vascular injury. In the healthy human population, plasma VWF levels vary widely. The important role of VWF is illustrated by individuals at the extremes of the normal distribution of plasma VWF concentrations where individuals with low VWF levels are more likely to present with mucocutaneous bleeding. Conversely, people with high VWF levels are at higher risk for venous thromboembolic disease, stroke, and coronary artery disease. This report will summarize recent advances in our understanding of environmental influences and the genetic control of VWF plasma variation in healthy and symptomatic populations and will also highlight the unanswered questions that are currently driving this field of study.

Download Full-text

Factor VIII/von Willebrand factor in subendothelium mediates platelet adhesion

Blood ◽

10.1182/blood.v65.4.823.bloodjournal654823 ◽

1985 ◽

Vol 65 (4) ◽

pp. 823-831 ◽

Cited By ~ 2

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.

Download Full-text

Inhibitor development in haemophilia A: the role of von Willebrand factor/factor VIII concentrates

Haemophilia ◽

10.1111/j.1365-2516.2007.01571.x ◽

2007 ◽

Vol 13 ◽

pp. 47-51 ◽

Cited By ~ 6

Author(s):

J. GOUDEMAND

Keyword(s):

Factor Viii ◽

Von Willebrand Factor ◽

Haemophilia A ◽

Inhibitor Development ◽

Factor Viii Concentrates ◽

Von Willebrand ◽

Willebrand Factor

Download Full-text

Microfibrils (MF) Platelet Interaction: Requirement Of Von Willebrand Factor In Platelet Adhesion To A Placenta Microfibrillar Component (PMC)

10.1055/s-0038-1652578 ◽

1981 ◽

Author(s):

F Fauvel ◽

Y J Legrand ◽

N Gutman ◽

J P Muh ◽

G Tobelem ◽

...

Keyword(s):

Von Willebrand Factor ◽

Platelet Adhesion ◽

Human Platelets ◽

Human Artery ◽

Von Willebrand ◽

Willebrand Factor ◽

Adhesion Of Platelets ◽

Aggregation Of Platelets

It has been shown that collagenase resistant arterial microfibrils (MF) are able to interact with platelets and therefore represents, besides collagen, a second thrombogenic structure in the vessel wall. In vitro observation using a PMC purified from the villosities of human placenta by a mechanical non denaturing procedure confirm this interaction between platelets and MF. PMC was homogenous under electron microscope (feltwork of MF with a mean diameter of 120 – 130 A) and was glycoproteic in nature. PMC were able to induce an aggregation of human platelets only if the platelets were in plasma. The role of Von Willebrand factor (F VIII/WF) as a cofactor of the aggregation of platelets by MF has been postulated from the fact that twice washed platelets from normal subject resuspended in PPP obtained from a severe Von Willebrand deficient patient were not aggregated by the PMC. Furthermore, aggregation was restored after resuspension of the same platelets in the PPP of the same patient 30 and 120 minutes after perfusion of cryoprecipitate (40 units F VIII/RA per kg).F VIII/WF mediates platelet adhesion after binding to subendothelium of human artery. Our observation strongly supports the idea that MF are the subendothelial components to which F VIII/WF binds, thus promoting an adhesion of platelets.

Download Full-text

Factor VIII-von Willebrand factor requires calcium for facilitation of platelet adherence

Blood ◽

10.1182/blood.v63.5.996.bloodjournal635996 ◽

1984 ◽

Vol 63 (5) ◽

pp. 996-103 ◽

Cited By ~ 1

Author(s):

KS Sakariassen ◽

M Ottenhof-Rovers ◽

JJ Sixma

Keyword(s):

Factor Viii ◽

Von Willebrand Factor ◽

Divalent Cations ◽

Platelet Adherence ◽

Human Arteries ◽

Platelet Spreading ◽

Von Willebrand ◽

Willebrand Factor ◽

Ristocetin Cofactor

The role of divalent cations in platelet adherence to deendothelialized human arteries in flowing blood was investigated in an annular perfusion chamber. Spreading of platelets on the subendothelium was impaired below 30 microM of free Ca2+ ions (Ca2+). When Ca2+ was replaced by Mg2+, adherence was unchanged in perfusates without exogenous factor VIII-von Willebrand factor (FVIII-vWF), but the ability of FVIII-vWF to support platelet adherence was lost. Binding of FVIII-vWF to the vessel wall was independent of divalent cations, but bound FVIII-vWF was only able to mediate adherence after exposure to Ca2+. Pretreatment of FVIII-vWF with the calcium chelator EGTA (10 mM) resulted in loss of the ability to facilitate platelet adherence, while the ristocetin cofactor activity remained intact. Full restoration of the ability to mediate platelet adherence could only be obtained by prolonged dialysis against Ca2+ in the millimolar range. These data indicate that divalent cations have at least two separate roles to play in supporting platelet adherence: (1) platelet spreading on the subendothelium requires Ca2+ or Mg2+; (2) FVIII-vWF should be exposed to Ca2+ to obtain its optimal biologic activity in supporting platelet adherence.

Download Full-text

Role of the mini-pool cryoprecipitate technology for cost-saving and guarantee of local Factor VIII, Von Willebrand Factor and Fibrinogen product supply: Egypt experience

Annals of Blood ◽

10.21037/aob.2018.02.07 ◽

2018 ◽

Vol 3 ◽

pp. 22-22 ◽

Cited By ~ 3

Author(s):

Magdy El Ekiaby ◽

Thierry Burnouf ◽

Hadi Goubran ◽

Mirjana Radosevich ◽

Ahmed El Ekiaby

Keyword(s):

Cost Saving ◽

Factor Viii ◽

Von Willebrand Factor ◽

Local Factor ◽

Von Willebrand ◽

Willebrand Factor

Download Full-text

Factor VIII/von Willebrand factor in subendothelium mediates platelet adhesion

Blood ◽

10.1182/blood.v65.4.823.823 ◽

1985 ◽

Vol 65 (4) ◽

pp. 823-831 ◽

Cited By ~ 106

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.

Download Full-text