Erworbenes von-Willebrand-Syndrom Typ 2A als Begleiterscheinung eines Dialyseshunts?

2011 ◽  
Vol 31 (02) ◽  
pp. 118-122
Author(s):  
F. Bach ◽  
S. Kuhlmann ◽  
B. Feidicker ◽  
M. U. Heim ◽  
C. Susemihl ◽  
...  
Keyword(s):  
Blood Flow ◽  
Shear Stress ◽  
Arteriovenous Fistula ◽  
Spontaneous Bleeding ◽  
Surgical Closure ◽  
Altered Blood ◽  
One Year ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Haemodialysis Treatment

SummaryAcquired von Willebrand’s disease (aVWD) is considered to be an underestimated cause of unexplained bleeding. Adsorption of von Willebrand factor (VWF) to tumour cells or hydroxyethyl starch and elimination of VWF by autoantibodies as well as shear stress-induced mechanical alteration of VWF with concomitant cleavage by enzymes may lead to an acquired deficiency of VWF and a bleeding disorder.We report a 39-year-old woman who developed spontaneous bleeding five years after surgical creation of an arteriovenous fistula (AVF) for haemodialysis treatment. AVWD type 2A was diagnosed after successful renal transplantation. One year after surgical closure of the AVF, the aVWD could not be verified again. Thus, the aVWD may have developed because of altered blood flow and shear stress inside the arteriovenous fistula.

scholarly journals Mechanical Forces Impacting Cleavage of Von Willebrand Factor in Laminar and Turbulent Blood Flow

Fluids ◽  
2021 ◽  
Vol 6 (2) ◽  
pp. 67
Author(s):  
Alireza Sharifi ◽  
David Bark
Keyword(s):  
Blood Flow ◽  
Shear Stress ◽  
Von Willebrand Factor ◽  
Circulatory Support ◽  
Acquired Von Willebrand Syndrome ◽  
Tensile Forces ◽  
Constant Shear Stress ◽  
Valve Diseases ◽  
Von Willebrand ◽  
Willebrand Factor

Von Willebrand factor (VWF) is a large multimeric hemostatic protein. VWF is critical in arresting platelets in regions of high shear stress found in blood circulation. Excessive cleavage of VWF that leads to reduced VWF multimer size in plasma can cause acquired von Willebrand syndrome, which is a bleeding disorder found in some heart valve diseases and in patients receiving mechanical circulatory support. It has been proposed that hemodynamics (blood flow) found in these environments ultimately leads to VWF cleavage. In the context of experiments reported in the literature, scission theory, developed for polymers, is applied here to provide insight into flow that can produce strong extensional forces on VWF that leads to domain unfolding and exposure of a cryptic site for cleavage through a metalloproteinase. Based on theoretical tensile forces, laminar flow only enables VWF cleavage when shear rate is large enough (>2800 s−1) or when VWF is exposed to constant shear stress for nonphysiological exposure times (>20 min). Predicted forces increase in turbulence, increasing the chance for VWF cleavage. These findings can be used when designing blood-contacting medical devices by providing hemodynamic limits to these devices that can otherwise lead to acquired von Willebrand syndrome.

Porcine von Willebrand Factor Binding to Human Platelet GPIb Induces Transmembrane Calcium Influx

1996 ◽  
Vol 75 (04) ◽  
pp. 655-660 ◽  
Author(s):  
Mario Mazzucato ◽  
Luigi De Marco ◽  
Paola Pradella ◽  
Adriana Masotti ◽  
Francesco I Pareti
Keyword(s):  
Monoclonal Antibody ◽  
Shear Stress ◽  
Platelet Aggregation ◽  
Von Willebrand Factor ◽  
Human Platelet ◽  
Platelet Glycoprotein ◽  
Dependent Manner ◽  
Transmembrane Flux ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryPorcine von Willebrand factor (P-vWF) binds to human platelet glycoprotein (GP) lb and, upon stirring (1500 rpm/min) at 37° C, induces, in a dose-dependent manner, a transmembrane flux of Ca2+ ions and platelet aggregation with an increase in their intracellular concentration. The inhibition of P-vWF binding to GP lb, obtained with anti GP lb monoclonal antibody (LJ-Ib1), inhibits the increase of intracellular Ca2+ concentration ([Ca2+]i) and platelet aggregation. This effect is not observed with LJ-Ib10, an anti GP lb monoclonal antibody which does not inhibit the vWF binding to GP lb. An anti GP Ilb-IIIa monoclonal antibody (LJ-CP8) shown to inhibit the binding of both vWF and fibrinogen to the GP IIb-IIIa complex, had only a slight effect on the [Ca2+]i rise elicited by the addition of P-vWF. No inhibition was also observed with a different anti GP IIb-IIIa monoclonal antibody (LJ-P5), shown to block the binding of vWF and not that of fibrinogen to the GP IIb-IIIa complex. PGE1, apyrase and indomethacin show a minimal effect on [Ca2+]i rise, while EGTA completely blocks it. The GP lb occupancy by recombinant vWF fragment rvWF445-733 completely inhibits the increase of [Ca2+]i and large aggregates formation. Our results suggest that, in analogy to what is seen with human vWF under high shear stress, the binding of P-vWF to platelet GP lb, at low shear stress and through the formation of aggregates of an appropriate size, induces a transmembrane flux of Ca2+, independently from platelet cyclooxy-genase metabolism, perhaps through a receptor dependent calcium channel. The increase in [Ca2+]i may act as an intracellular message and cause the activation of the GP IIb-IIIa complex.

An in vivo Model for the Assessment of Acute Fibrinolytic Capacity of the Endothelium

1997 ◽  
Vol 78 (04) ◽  
pp. 1242-1248 ◽  
Author(s):  
David E Newby ◽  
Robert A Wright ◽  
Christopher A Ludlam ◽  
Keith A A Fox ◽  
Nicholas A Boon ◽  
...  
Keyword(s):  
Blood Flow ◽  
Substance P ◽  
Sodium Nitroprusside ◽  
Plasma Concentrations ◽  
In Vivo Model ◽  
Forearm Circulation ◽  
Von Willebrand ◽  
Local Release ◽  
Willebrand Factor

SummaryThe effects on blood flow and plasma fibrinolytic and coagulation parameters of intraarterial substance P, an endothelium dependent vasodilator, and sodium nitroprusside, a control endothelium independent vasodilator, were studied in the human forearm circulation. At subsystemic locally active doses, both substance P (2-8 pmol/min) and sodium nitroprusside (2-8 μg/min) caused dose-dependent vasodilatation (p <0.001 for both) without affecting plasma concentrations of PAI-1, von Willebrand factor antigen or factor VIII:C activity. Substance P caused local increases in t-PA antigen and activity (p <0.001) in the infused arm while sodium nitroprusside did not. At higher doses, substance P increased blood flow and t-PA concentrations in the noninfused arm. We conclude that brief, locally active and subsystemic infusions of intraarterial substance P cause a rapid and substantial local release of t-PA which appear to act via a flow and nitric oxide independent mechanism. This model should provide a useful and selective method of assessing the in vivo capacity of the forearm endothelium to release t-PA acutely.

scholarly journals Platelet Aggregation Induced by a Monoclonal Antibody to the A1 Domain of von Willebrand Factor

Blood ◽  
1998 ◽  
Vol 91 (10) ◽  
pp. 3792-3799 ◽  
Author(s):  
Hilde Depraetere ◽  
Nadine Ajzenberg ◽  
Jean-Pierre Girma ◽  
Catherine Lacombe ◽  
Dominique Meyer ◽  
...  
Keyword(s):  
Shear Stress ◽  
Platelet Aggregation ◽  
Von Willebrand Factor ◽  
Inhibitory Effect ◽  
Platelet Glycoprotein ◽  
Rotational Viscometer ◽  
Induce Platelet Aggregation ◽  
Static Conditions ◽  
Von Willebrand ◽  
Willebrand Factor

Shear-induced platelet aggregation (SIPA) involves von Willebrand Factor (vWF) binding to platelet glycoprotein (GP)Ib at high shear stress, followed by the activation of αIIbβ3. The purpose of this study was to determine the vWF sequences involved in SIPA by using monoclonal antibodies (MoAbs) to vWF known to interfere with its binding to GPIb and to αIIbβ3. Washed platelets were exposed to shear rates between 100 and 4,000 seconds−1 in a rotational viscometer. SIPA was quantitated by flow cytometry as the disappearance of single platelets (DSP) in the sheared sample in the presence of vWF, relative to a control in the absence of shear and vWF. At a shear rate of 4,000 seconds−1, DSP was increased from 5.9% ± 3.5% in the absence of vWF to 32.7% ± 6.3% in the presence of vWF. This increase in SIPA was not associated with an elevation of P-selectin expression. vWF-dependent SIPA was completely abolished by MoAb 6D1 to GPIb and partially inhibited by MoAb 10E5 to αIIbβ3. Three MoAbs to vWF were compared for their effect on SIPA at 4,000 seconds−1 in the presence of vWF: MoAb 328, known to block vWF binding to GPIb in the presence of ristocetin, MoAb 724 blocking vWF binding to GPIb in the presence of botrocetin, and MoAb 9, an inhibitor of vWF binding to αIIbβ3. Similar to the effect of MoAb 6D1, MoAb 328 completely inhibited the effect of vWF, whereas MoAb 9 had a partial inhibitory effect, as MoAb 10E5 did. In contrast, MoAb 724, as well as its F(ab′)2 fragments, promoted shear-dependent platelet aggregation (165% of the DSP value obtained in the absence of MoAb 724), indicating that MoAb 724 was responsible for an enhanced aggregation, which was independent of binding to the platelet Fcγ receptor. In addition, the enhancement of aggregation induced by MoAb 724 was abrogated by MoAb 6D1 or 10E5 to the level of SIPA obtained in the presence of vWF incubated with a control MoAb to vWF. Finally, the activating effect of MoAb 724 was also found under static conditions at ristocetin concentrations too low to induce platelet aggregation. Our results suggested that on binding to a botrocetin-binding site on vWF, MoAb 724 mimics the effect of botrocetin by inducing an active conformation of vWF that is more sensitive to shear stress or to low ristocetin concentration.

Computational Mechanical Analysis of the Platelets Behavior in the Blood Flow Using Discrete Element Method

2000 ◽  
Author(s):  
Hisako Miyazaki ◽  
Hao Liu ◽  
Takami Yamaguchi
Keyword(s):  
Blood Flow ◽  
Vessel Wall ◽  
Thrombus Formation ◽  
Mechanical Analysis ◽  
Soluble Form ◽  
Blood Constituents ◽  
Fibrin Network ◽  
Insoluble Form ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Platelets play an important role in blood coagulation, particularly in the formation of primary thrombi. It is thought that the aggregation of platelets, which initiates primary thrombi formation, is mediated by a macromolecule called von Willebrand Factor (vWF). vWF is a long chain macromolecule that exists in the blood flow as a soluble form and in the vessel wall as an insoluble form. Figure 1 schematically shows normal (a) and pathological (b) thrombus formation processes as illustrated by Ikeda (1998) In both cases, platelets adhere to the injured vessel wall and then form a thrombus in cooperation with the fibrin network, red cells, and other blood constituents. vWF is thought to play a more important role in pathological thrombosis formation than in the normal hemostatic process, particularly due to its ability to react to hemodynamic stress.

Vasomotor responses in chronically hyperperfused and hypoperfused rat mesenteric arteries

1998 ◽  
Vol 274 (4) ◽  
pp. H1301-H1307 ◽  
Author(s):  
Fabrice Pourageaud ◽  
Jo G. R. De Mey
Keyword(s):  
Blood Flow ◽  
Shear Stress ◽  
Sodium Nitroprusside ◽  
Arginine Vasopressin ◽  
Side Branch ◽  
Mesenteric Arteries ◽  
Low Flow ◽  
Basal Diameter ◽  
Lower Shear ◽  
Altered Blood

We evaluated the reactivity of small arteries after remodeling induced by elevated or reduced blood flow. In 6-wk-old rats, every other first-order side branch of the superior mesenteric artery was ligated near the bifurcation of second-order branches. Four weeks after surgery, vessels that had been exposed to high flow (HF) or low flow (LF) were isolated and mounted in a pressure myograph at 100 mmHg and were compared with vessels from sham-operated rats (Sham). In HF: 1) basal lumen diameter was increased; 2) sensitivity to norepinephrine, arginine vasopressin, and perivascular nerve stimulation was not modified; 3) maximal constrictor responses (Δ diameter) to these stimuli and 125 mM K+ were increased; and 4) sensitivity and maximal dilator responses to sodium nitroprusside, acetylcholine, and flow were not modified. In LF: 1) basal diameter was reduced; 2) sensitivity to constrictor stimuli was not altered; 3) maximal responses to all vasoconstrictors except arginine vasopressin were reduced; and 4) sensitivity but not maximal dilator responses to sodium nitroprusside and acetylcholine was reduced. During acute flow-induced dilatations, lower shear stress was maintained in HF (48 ± 7 dyn/cm2) than in Sham (63 ± 10 dyn/cm2), but no shear stress regulation was observed in LF. These observations indicate that arterial structural responses to altered blood flow are accompanied by modified reactivity of the arterial smooth muscle, which entails changes in responsiveness to neurogenic and endothelium-dependent stimuli.

Glycoprotein V-Deficient Platelets Have Undiminished Thrombin Responsiveness and Do Not Exhibit a Bernard-Soulier Phenotype

Blood ◽  
1999 ◽  
Vol 94 (12) ◽  
pp. 4112-4121 ◽  
Author(s):  
Mark L. Kahn ◽  
Thomas G. Diacovo ◽  
Dorothy F. Bainton ◽  
Francois Lanza ◽  
JoAnn Trejo ◽  
...  
Keyword(s):  
Wild Type ◽  
Spontaneous Bleeding ◽  
Atp Secretion ◽  
Platelet Receptor ◽  
High Concentrations ◽  
And Function ◽  
A1 Domain ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Adhesion Of Platelets

Abstract Adhesion of platelets to extracellular matrix via von Willebrand factor (vWF) and activation of platelets by thrombin are critical steps in hemostasis. Glycoprotein (GP) V is a component of the GPIb-V-IX complex, the platelet receptor for vWF. GPV is also cleaved by thrombin. Deficiency of GPIb or GPIX results in Bernard-Soulier syndrome (BSS), a bleeding disorder in which platelets are giant and have multiple functional defects. Whether GPV-deficiency might also cause BSS is unknown as are the roles of GPV in platelet-vWF interaction and thrombin signaling. We report that GPV-deficient mice developed normally, had no evidence of spontaneous bleeding, and had tail bleeding times that were not prolonged compared with wild-type mice. GPV-deficient platelets were normal in size and structure as assessed by flow cytometry and electron microscopy. GPV-deficient and wild-type platelets were indistinguishable in botrocetin-mediated platelet agglutination and in their ability to adhere to mouse vWF A1 domain. Platelet aggregation and ATP secretion in response to low and high concentrations of thrombin were not decreased in GPV-deficient platelets compared with wild-type. Our results show that (1) GPV is not necessary for GPIb expression and function in platelets and that GPV deficiency is not likely to be a cause of human BSS and (2) GPV is not necessary for robust thrombin signaling. Whether redundancy accounts for the lack of phenotype of GPV-deficiency or whether GPV serves subtle or as yet unprobed functions in platelets or other cells remains to be determined.

scholarly journals Blocking von Willebrand factor free thiols inhibits binding to collagen under high and pathological shear stress

2020 ◽  
Author(s):  
Harrison E. R. O’Brien ◽  
X. Frank Zhang ◽  
Maximo Sanz‐Hernandez ◽  
Alain Chion ◽  
Susan Shapiro ◽  
...  
Keyword(s):  
Shear Stress ◽  
Von Willebrand Factor ◽  
Von Willebrand ◽  
Willebrand Factor

von Willebrand Factor Ristocetin Cofactor Activity Correlates with Platelet Function in a High Shear Stress System

2000 ◽  
Vol 84 (10) ◽  
pp. 727-728 ◽  
Author(s):  
Agnès Veyradier ◽  
Edith Fressinaud ◽  
Catherine Boyer-Neumann ◽  
Marc Trossaert ◽  
Dominique Meyer
Keyword(s):  
Shear Stress ◽  
Von Willebrand Factor ◽  
Stress System ◽  
High Shear ◽  
High Shear Stress ◽  
Cofactor Activity ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Ristocetin Cofactor ◽  
Ristocetin Cofactor Activity
Sign in / Sign up

Export Citation Format

Share Document