DETERMINING THE ROLE OF VON WILLEBRAND FACTOR IN THROMBOTIC POST-TRANSPLANTATION COMPLICATIONS USING EX VIVO LUNG PERFUSION SYSTEM

2021 ◽  
Vol 37 (10) ◽  
pp. S113-S114
Author(s):  
P Alavi ◽  
S Himmat ◽  
M Buchko ◽  
N Aboelnazar ◽  
J Nagendran ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Ex Vivo ◽  
Lung Perfusion ◽  
Perfusion System ◽  
Post Transplantation ◽  
Ex Vivo Lung Perfusion ◽  
Transplantation Complications ◽  
Von Willebrand ◽  
Willebrand Factor

scholarly journals Sickle erythrocyte-endothelial interactions in microcirculation: the role of von Willebrand factor and implications for vasoocclusion

Blood ◽  
1993 ◽  
Vol 81 (9) ◽  
pp. 2429-2438 ◽  
Author(s):  
DK Kaul ◽  
RL Nagel ◽  
D Chen ◽  
HM Tsai
Keyword(s):  
Von Willebrand Factor ◽  
Microvascular Obstruction ◽  
Ex Vivo ◽  
Peripheral Resistance ◽  
Pronounced Increase ◽  
Sickle Erythrocyte ◽  
Large Molecular Weight ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract To determine the role of von Willebrand factor (vWF) in adhesion of sickle (SS) erythrocytes in microvascular flow conditions, we have perfused the ex vivo mesocecum vasculature of the rat with desmopressin, an analogue of vasopressin that causes the release of endothelial vWF. Analysis of vWF in the venous effluent of the isolated vasculature showed mainly the presence of extra-large molecular weight forms characteristic of endothelial vWF, which in the presence of desmopressin showed an average increase of 54%. Also, desmopressin induced a significant increase in adhesion of washed oxygenated (oxy) unseparated SS erythrocytes, accompanied by a persistent microvascular obstruction and a pronounced increase in the peripheral resistance (PRU). In contrast, infusion of SS deformable discocytes (SS2) in desmopressin-perfused vasculature resulted in a significant adhesion but not in persistent vasoocclusion, showing that SS2 discocytes alone are not sufficient for microvascular obstruction. Furthermore, SS4 erythrocytes (dense discocytes and irreversibly sickled erythrocytes) caused a persistent microvascular blockage and a significantly higher PRU than SS2 discocytes. However, the increase in PRU for SS4 erythrocytes following desmopressin treatment was 50% less compared with a corresponding increase for SS2 discocytes over the control values, which showed a smaller effect of desmopressin on the hemodynamic behavior of SS4 dense erythrocytes. Incubation of desmopressin-treated vasculature with anti-vWF antibodies resulted in a pronounced decrease in adhesion and significantly improved hemodynamic behavior of SS cells. Also, in untreated vasculature, similarly incubated with anti-vWF antibodies, there was almost complete inhibition of adhesion. Under the described perfusion conditions, antibodies to fibronectin and thrombospondin, as well as incubation of SS erythrocytes with anti-vWF antibodies did not affect adhesion. These results are compatible with a model for SS vasoocclusion in which extra- large vWF-mediated adhesion of deformable SS erythrocytes is the first step followed by an accelerated entrapment of dense SS erythrocytes.

scholarly journals Sickle erythrocyte-endothelial interactions in microcirculation: the role of von Willebrand factor and implications for vasoocclusion

Blood ◽  
1993 ◽  
Vol 81 (9) ◽  
pp. 2429-2438 ◽  
Author(s):  
DK Kaul ◽  
RL Nagel ◽  
D Chen ◽  
HM Tsai
Keyword(s):  
Von Willebrand Factor ◽  
Microvascular Obstruction ◽  
Ex Vivo ◽  
Peripheral Resistance ◽  
Pronounced Increase ◽  
Sickle Erythrocyte ◽  
Large Molecular Weight ◽  
Von Willebrand ◽  
Willebrand Factor

To determine the role of von Willebrand factor (vWF) in adhesion of sickle (SS) erythrocytes in microvascular flow conditions, we have perfused the ex vivo mesocecum vasculature of the rat with desmopressin, an analogue of vasopressin that causes the release of endothelial vWF. Analysis of vWF in the venous effluent of the isolated vasculature showed mainly the presence of extra-large molecular weight forms characteristic of endothelial vWF, which in the presence of desmopressin showed an average increase of 54%. Also, desmopressin induced a significant increase in adhesion of washed oxygenated (oxy) unseparated SS erythrocytes, accompanied by a persistent microvascular obstruction and a pronounced increase in the peripheral resistance (PRU). In contrast, infusion of SS deformable discocytes (SS2) in desmopressin-perfused vasculature resulted in a significant adhesion but not in persistent vasoocclusion, showing that SS2 discocytes alone are not sufficient for microvascular obstruction. Furthermore, SS4 erythrocytes (dense discocytes and irreversibly sickled erythrocytes) caused a persistent microvascular blockage and a significantly higher PRU than SS2 discocytes. However, the increase in PRU for SS4 erythrocytes following desmopressin treatment was 50% less compared with a corresponding increase for SS2 discocytes over the control values, which showed a smaller effect of desmopressin on the hemodynamic behavior of SS4 dense erythrocytes. Incubation of desmopressin-treated vasculature with anti-vWF antibodies resulted in a pronounced decrease in adhesion and significantly improved hemodynamic behavior of SS cells. Also, in untreated vasculature, similarly incubated with anti-vWF antibodies, there was almost complete inhibition of adhesion. Under the described perfusion conditions, antibodies to fibronectin and thrombospondin, as well as incubation of SS erythrocytes with anti-vWF antibodies did not affect adhesion. These results are compatible with a model for SS vasoocclusion in which extra- large vWF-mediated adhesion of deformable SS erythrocytes is the first step followed by an accelerated entrapment of dense SS erythrocytes.

scholarly journals The role of von Willebrand factor in breast cancer metastasis

2021 ◽  
Vol 14 (4) ◽  
pp. 101033
Author(s):  
Chia Yin Goh ◽  
Sean Patmore ◽  
Albert Smolenski ◽  
Jane Howard ◽  
Shane Evans ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Von Willebrand Factor ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Von Willebrand ◽  
Willebrand Factor

Role of Platelet Membrane Glycoproteins and Von Willebrand Factor in Adhesion of Platelets to Subendothelium and Collagen

1987 ◽  
Vol 516 (1 Blood in Cont) ◽  
pp. 52-65 ◽  
Author(s):  
KJELL S. SAKARIASSEN ◽  
EDITH FRESSINAUD ◽  
JEAN-PIERRE GIRMA ◽  
DOMINIQUE MEYER ◽  
HANS R. BAUMGARTNER
Keyword(s):  
Von Willebrand Factor ◽  
Platelet Membrane ◽  
Membrane Glycoproteins ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Adhesion Of Platelets

The Role of Ex-vivo Lung Perfusion (EVLP) in Lung Transplantation

2020 ◽  
pp. 977-986
Author(s):  
Daniel Mansour ◽  
Sophia Roberts ◽  
Madonna Lee ◽  
Bassam Shukrallah ◽  
Bryan A. Whitson
Keyword(s):  
Lung Transplantation ◽  
Ex Vivo ◽  
Lung Perfusion ◽  
Ex Vivo Lung Perfusion

scholarly journals Partial characterization of a binding site for von Willebrand factor on glycocalicin

Blood ◽  
1986 ◽  
Vol 67 (1) ◽  
pp. 19-26 ◽  
Author(s):  
AD Michelson ◽  
J Loscalzo ◽  
B Melnick ◽  
BS Coller ◽  
RI Handin
Keyword(s):  
Binding Site ◽  
Von Willebrand Factor ◽  
Platelet Adhesion ◽  
Binding Activity ◽  
Proteolytic Fragment ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Beta Galactosidase

The binding of von Willebrand factor (vWF) to platelet membrane glycoprotein Ib (GpIb) facilitates platelet adhesion to vascular subendothelium. In this study, we provide evidence that the vWF binding site is on glycocalicin (GC), a proteolytic fragment of GpIb, and we examine the role of the carbohydrate portion of GC on that binding. The binding to platelets of 6D1, a monoclonal antibody that recognizes an epitope on GpIb and blocks ristocetin-induced vWF binding to platelets, was inhibited by purified GC. In addition, purified GC inhibited ristocetin-dependent binding of 125I-labeled vWF to platelets. Since GC contains 60% carbohydrate by weight, we assessed the role of carbohydrate sequences on its interaction with antibody 6D1 and vWF. Based on the known sequence of the major oligosaccharide chain of GC--N- acetyl neuraminic acid, galactose, N-acetyl glucosamine, N-acetyl galactosamine--we treated GC sequentially with neuraminidase, beta- galactosidase, and beta-N-acetylglucosaminidase. Removal of sialic acid and galactose residues did not affect GC binding. Removal of N-acetyl glucosamine residues did not affect GC binding to 6D1 but did decrease the ability of GC to inhibit vWF binding to platelets, increasing the concentration needed to inhibit binding by 50% (IC50) 40-fold. This suggests that a portion of the oligosaccharide chains on GC contributes to the vWF binding activity of this molecule.

scholarly journals Platelet von Willebrand factor: evidence for its involvement in platelet adhesion to collagen

Blood ◽  
1987 ◽  
Vol 70 (4) ◽  
pp. 1214-1217
Author(s):  
E Fressinaud ◽  
D Baruch ◽  
C Rothschild ◽  
HR Baumgartner ◽  
D Meyer
Keyword(s):  
Shear Rate ◽  
Von Willebrand Factor ◽  
Platelet Adhesion ◽  
Von Willebrand Disease ◽  
High Shear ◽  
Shear Rates ◽  
High Shear Rates ◽  
Von Willebrand ◽  
Willebrand Factor

Although it is well established that plasma von Willebrand Factor (vWF) is essential to platelet adhesion to subendothelium at high shear rates, the role of platelet vWF is less clear. We studied the respective role of both plasma and platelet vWF in mediating platelet adhesion to fibrillar collagen in a parallel-plate perfusion chamber. Reconstituted blood containing RBCs, various mixtures of labeled washed platelets and plasma from controls or five patients with severe von Willebrand disease (vWD), was perfused through the chamber for five minutes at a shear rate of 1,600 s-1. Platelet-collagen interactions were estimated by counting the radioactivity in deposited platelets and by quantitative morphometry. When the perfusate consisted of normal platelets suspended in normal plasma, platelet deposition on the collagen was 24.7 +/- 3.6 X 10(6)/cm2 (mean +/- SEM, n = 6). Significantly less deposition (16 +/- 2.3) was observed when vWD platelets were substituted for normal platelets. In mixtures containing vWD plasma, significantly greater deposition (9 +/- 2.2) was obtained with normal than with vWD platelets (1 +/- 0.4) demonstrating a role for platelet vWF in mediating the deposition of platelets on collagen. Morphometric analysis confirmed these data. Our findings indicate that platelet, as well as plasma, vWF mediates platelet-collagen interactions at a high shear rate.

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