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.

Computational Mechanical Simulation of the Aggregation and Dissociation of Platelets Mediated by von Willebrand Factor

2002 ◽  
Author(s):  
K. Yano ◽  
T. Yamaguchi
Keyword(s):  
Von Willebrand Factor ◽  
Vessel Wall ◽  
Thrombus Formation ◽  
Soluble Form ◽  
Blood Constituents ◽  
Fibrin Network ◽  
Insoluble Form ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Aggregation Of Platelets

Platelets play an important role in blood coagulation, particularly in the formation of primary thrombi. The aggregation of platelets, which initiates primary thrombi formation, is thought to be mediated by the von Willebrand factor (vWF). The vWF is a long-chain macromolecule that exists in a soluble form in the blood flow and an insoluble form in the vessel wall. Figure 1 schematically shows normal (a) and pathological (b) thrombus formation processees. 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. The vWF plays a more important role in pathological thrombosis formation than in the normal hemostatic process, due to its ability to sense and react to hemodynamic stress.

Lack of Stability of Aggregates after Thrombin-Induced Reaggregation of Thrombin-Degranulated Platelets

1992 ◽  
Vol 67 (04) ◽  
pp. 453-457 ◽  
Author(s):  
Raelene L Kinlough-Rathbone ◽  
Marian A Packham ◽  
Dennis W Perry ◽  
J Fraser Mustard ◽  
Marco Cattaneo
Keyword(s):  
Von Willebrand Factor ◽  
Platelet Rich Plasma ◽  
Thrombus Formation ◽  
Aggregate Stability ◽  
Relative Importance ◽  
Platelet Aggregates ◽  
The Stability ◽  
Von Willebrand ◽  
Induced Aggregation ◽  
Willebrand Factor

SummaryThe stability of platelet aggregates is influenced by the extent of the release of granule contents; if release is extensive and aggregation is prolonged, deaggregation is difficult to achieve. The relative importance of the contributions of released substances to aggregate stability are not known, although stable thrombin-induced aggregates form in platelet-rich plasma from patients with barely detectable plasma or platelet fibrinogen, and ADP stabilizes thrombin-induced aggregates of platelets from patients with delta storage pool deficiency which otherwise deaggregate more readily than normal platelets. We degranulated platelets with thrombin (0.9 U/ml caused greater than 90% loss of delta and alpha granule contents) and recovered them as individual platelets in fresh medium. The degranulated platelets were reaggregated by thrombin (2 U/ml). To prevent continuing effects of thrombin, FPRCH2C1 was added when thrombin-induced aggregation of thrombin-degranulated platelets reached its maximum. EDTA (5 mM) or EGTA (5 mM) added at maximum aggregation did not deaggregate these platelets, indicating that the stability of these aggregates does not depend on Ca2+ in the medium. Whereas with control platelets a combination of PGE1 (10 μM) and chymotrypsin(10 U/ml) was required for deaggregation, with thrombin-degranulated platelets either PGE1 or chymo-trypsin alone caused extensive deaggregation. The rate and extent of deaggregation of thrombin-degranulated platelets by a combination of PGE1 and chymotrypsin was greater than with control platelets.Electron microscope gold immunocytochemistry using antihuman fibrinogen IgG, anti-von Willebrand factor and anti-fibronectin showed a) that fibrinogen in the vacuoles of degranulated platelets was visible at focal points of platelet contact in the aggregates, but that large areas of platelet contact had no fibrinogen detectable between them; and b) in comparison to fibrinogen, little fibronectin or von Willebrand factor (vWf) was detectable in the platelets.Since the linkages between thrombin-degranulated platelets reaggregated by thrombin can be disrupted either by raising cAMP (thus making glycoprotein IIb/IIIa unavailable) or by proteolysis, these linkages are less stable than those formed between normal platelets. It might therefore be expected that platelets that take part in thrombus formation and then recirculate are likely to form less stable thrombi than platelets that have not released their granule contents.

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 Immunohistological Evaluation of Von Willebrand Factor in the Left Atrial Endocardium and Atrial Thrombi from Cats with Cardiomyopathy

Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1240
Author(s):  
Wan-Ching Cheng ◽  
Lois Wilkie ◽  
Tsumugi Anne Kurosawa ◽  
Melanie Dobromylskyj ◽  
Simon Lawrence Priestnall ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Left Atrial ◽  
Thrombus Formation ◽  
Clinical Signs ◽  
Naturally Occurring ◽  
Feline Model ◽  
Von Willebrand ◽  
And Control ◽  
Endocardial Endothelium ◽  
Willebrand Factor

Aortic thromboembolism (ATE) occurs in cats with cardiomyopathy and often results in euthanasia due to poor prognosis. However, the underlying predisposing mechanisms leading to left atrial (LA) thrombus formation are not fully characterised. von Willebrand Factor (vWF) is a marker of endothelium and shows increased expression following endothelial injury. In people with poor LA function and LA remodelling, vWF has been implicated in the development of LA thrombosis. In this study we have shown (1) the expression of endocardial vWF protein detected using immunohistofluorescence was elevated in cats with cardiomyopathy, LA enlargement (LAE) and clinical signs compared to cats with subclinical cardiomyopathy and control cats; (2) vWF was present at the periphery of microthrombi and macrothrombi within the LA where they come into contact with the LA endocardium and (3) vWF was integral to the structure of the macrothrombi retrieved from the atria. These results provide evidence for damage of the endocardial endothelium in the remodelled LA and support a role for endocardial vWF as a pro-thrombotic substrate potentially contributing to the development of ATE in cats with underlying cardiomyopathy and LAE. Results from this naturally occurring feline model may inform research into human thrombogenesis.

Signaling through GP Ib-IX-V activates αIIbβ3 independently of other receptors

Blood ◽  
2004 ◽  
Vol 103 (9) ◽  
pp. 3403-3411 ◽  
Author(s):  
Ana Kasirer-Friede ◽  
Maria Rita Cozzi ◽  
Mario Mazzucato ◽  
Luigi De Marco ◽  
Zaverio M. Ruggeri ◽  
...  
Keyword(s):  
Tyrosine Phosphorylation ◽  
Platelet Adhesion ◽  
Thrombus Formation ◽  
Signaling Proteins ◽  
Phosphatidylinositol 3 Kinase ◽  
Kinase C ◽  
A1 Domain ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Pharmacologic Inhibition

Abstract Platelet adhesion to von Willebrand factor (VWF) activates αIIbβ3, a prerequisite for thrombus formation. However, it is unclear whether the primary VWF receptor, glycoprotein (GP) Ib-IX-V, mediates αIIbβ3 activation directly or through other signaling proteins physically associated with it (eg, FcR γ-chain), possibly with the contribution of other agonist receptors and of VWF signaling through αIIbβ3. To resolve this question, human and GP Ibα transgenic mouse platelets were plated on dimeric VWF A1 domain (dA1VWF), which engages only GP Ib-IX-V, in the presence of inhibitors of other agonist receptors. Platelet adhesion to dA1VWF induced Src kinase-dependent tyrosine phosphorylation of the FcR γ-chain and the adapter molecule, ADAP, and triggered intracellular Ca2+ oscillations and αIIbβ3 activation. Inhibition of Ca2+ oscillations with BAPTA-AM prevented αIIbβ3 activation but not tyrosine phosphorylation. Pharmacologic inhibition of protein kinase C (PKC) or phosphatidylinositol 3-kinase (PI 3-kinase) prevented αIIbβ3 activation but not Ca2+ oscillations. Inhibition of Src with 2 distinct compounds blocked all responses downstream of GP Ib-IX-V under static or flow conditions. However, dA1VWF-induced responses were reduced only slightly in GP Ibα transgenic platelets lacking FcR γ-chain. These data establish that GP Ib-IX-V itself can signal to activate αIIbβ3, through sequential actions of Src kinases, Ca2+ oscillations, and PI 3-kinase/PKC. (Blood. 2004;103:3403-3411)

Levels of von Willebrand factor and ADAMTS13 determine clinical outcome after cardioversion for atrial fibrillation

2011 ◽  
Vol 105 (03) ◽  
pp. 435-443 ◽  
Author(s):  
Veronika Bruno ◽  
Rudolf Jarai ◽  
Susanne Gruber ◽  
Thomas Höchtl ◽  
Ivan Brozovic ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Von Willebrand Factor ◽  
Platelet Adhesion ◽  
Independent Predictor ◽  
Thrombus Formation ◽  
Critical Role ◽  
Inverse Correlation ◽  
Von Willebrand ◽  
Rhythm Stability ◽  
Willebrand Factor

SummaryVon Willebrand factor (vWF) plays an essential role in platelet adhesion and thrombus formation. Patients with atrial fibrillation (AF) exhibit higher plasma vWF and lower ADAMTS13 antigen levels compared to controls. Little is known about vWF and ADAMTS13 in AF patients treated with cardioversion (CV). Thus we investigated the alterations of plasma vWF and ADAMTS13 after CV and evaluated the predictive value of these parameters for recurrence of AF. In this observational study we determined plasma levels of vWF and ADAMTS13 in 77 patients before and immediately after CV, as well as 24 hours (h) and six weeks thereafter, by means of commercially available assays. The vWF/ ADAMTS13-ratio was significantly elevated immediately after CV (p=0.02) and 24 h after CV (p=0.002) as compared to baseline levels. ADAMTS13, 24 h after CV, exhibited a significant association with recurrence of AF (HR: 0.97; p=0.037). Accordingly, tertiles of ADAMTS13 showed a stepwise inverse correlation with the risk of recurrent AF (HR: 0.50; p=0.009). After adjustment for confounders, ADAMTS13 remained significant as an independent predictor of recurrent AF (HR: 0.61; p=0.047). Similarly, the vWF/ADAMTS13-ratio, 24 h after CV, was associated with rhythm stability and remained an independent predictor of recurrent AF (HR: 1.88; p=0.028). The regulation of vWF and its cleaving protease ADAMTS13 after CV might play a critical role in producing a pro-thrombotic milieu immediately after CV for AF. Since ADAMTS13 plasma concentration and the vWF/ADAMTS13-ratio are independently associated with rhythm stability, these indexes might be used for prediction of recurrence of AF.

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