Platelet Activation and Free Emboli Formation in Flow Past Mechanical Heart Valves

2002 ◽  
Author(s):  
Danny Bluestein ◽  
Wei Yin ◽  
Jolyon Jesty ◽  
Adam E. Saltman ◽  
Irvin B. Krukenkamp ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Heart Valves ◽  
Left Ventricular ◽  
Mechanical Heart Valves ◽  
Shear Stresses ◽  
Platelet Activity ◽  
Flow Past ◽  
Activity State ◽  
Valve Implantation

Numerical studies, in vitro, and in vivo measurements were conducted, aimed at quantifying free emboli formation and procoagulant properties of platelets induced by flow past mechanical heart valves (MHV). Pulsatile turbulent flow simulation was conducted past a St. Jude medical MHV in the aortic position, to study the effects of valve implantation technique on the thromboembolic potential of the valve. A misaligned valve with subannualarly sutured pledgets produced accelerating jet flow through the valve orifices and a wider wake of shed vortices. Shear stress histories of platelets along turbulent trajectories exposed the platelets to elevated shear stresses around the leaflets, leading them to entrapment within the shed vortices. In vitro platelet studies were conducted past the MHV mounted in a recirculation flow loop and in a model of left ventricular assist device (LVAD), using an innovative platelet activity state (PAS) assay. The platelet activation significantly increased as a function of the recirculation time past the valve, and as compared to controls. Transcranial Doppler (TCD) measurements were conducted in the carotid artery of sheep with implanted MHV, showing marked increase in the number of HITS (High Intensity Transient Signals) signifying the passage of free emboli generated by the valve. The HITS were analyzed to distinguish between gaseous and thrombi emboli. Finally, platelet activity state measurements were conducted with sheep platelets, showing marked increase of platelet activation after valve implantation.

Platelet Activation in Flow Past Mechanical Heart Valves

2001 ◽  
Author(s):  
Danny Bluestein ◽  
Jolyon Jesty ◽  
Adam E. Saltman ◽  
Irvin B. Krukenkamp ◽  
Krishnamurthy Suresh
Keyword(s):  
Platelet Activation ◽  
Heart Valves ◽  
Mechanical Heart Valves ◽  
Implantation Technique ◽  
Shear Stresses ◽  
Flow Past ◽  
Activity State ◽  
Valve Implantation

Abstract Numerical studies, in vitro, and in vivo measurements were conducted, aimed at quantifying free emboli formation and procoagulant properties of platelets induced by flow past mechanical heart valves (MHV). Pulsatile turbulent flow simulation was conducted past a St. Jude medical MHV in the aortic position, to study the effects of valve implantation technique on the thromboembolic potential of the valve. A misaligned valve with subannualarly sutured pledgets produced accelerating jet flow through the valve orifices and a wider wake of shed vortices. Shear stress histories of platelets along turbulent trajectories exposed the platelets to elevated shear stresses around the leaflets, leading them to entrapment within the shed vortices. In vitro platelet studies were conducted past the MHV mounted in a recirculation flow loop, by measuring the platelets ability to support the activation of acetylated human prothrombin by factor xa, which enables sequestering flow induced effects and quantification of the platelets activity state. The platelet activation state increased monotonically as a function of the recirculation time past the valve, as measured by the thrombin generation rates in the assay. Finally, platelet activity state measurements were conducted in vivo, from a sheep with an implanted MHV, showing marked increase of platelet activation after valve implantation.

Effects of Valve Design and Orientation on Flow Induced Platelet Activation in Mechanical Heart Valves

2004 ◽  
Author(s):  
Wei Yin ◽  
Yared Alemu ◽  
Jolyon Jesty ◽  
Danny Bluestein
Keyword(s):  
Shear Stress ◽  
Heart Valves ◽  
Mechanical Heart Valve ◽  
Cumulative Effect ◽  
Left Ventricular ◽  
Platelet Activity ◽  
Ventricular Assist ◽  
Activity State ◽  
Blood Flow Patterns

A study was conducted to estimate the thromboembolic potential of different Mechanical Heart Valve (MHV) designs and the effect of valve orientation (valve axial misalignment during implantation) on it. CFD simulations of turbulent, transient, non-Newtonian blood flow patterns generated by two types of MHVs (monoleaflet and bileaflet) and the effect of valve orientation were conducted using the Wilcox k-ω turbulence model. Platelet shear stress histories (cumulative effect of shear stress and time) were calculated and averaged over a large number of platelet trajectories within the flow field, and compared with in vitro Platelet Activity State (PAS) measurements conducted in a left ventricular assist device (LVAD) model. Platelets were circulated in the LVAD with Carbomedics bileaflet and Bjork-Shiley monoleaflet MHVs correspondingly. The PAS measurement indicated that PAS induced by the tilted St. Jude bileaflet MHV and the untilted valve was very similar (P>0.1). The bileaflet MHV activated platelets at a rate of more than 2-fold than that observed with the monoleaflet MHV (P<0.05). This confirmed the CFD platelet shear stress histories, which clearly indicated a higher level of stimulation of platelets for the bileaflet MHV.

Evaluation of Platelet Activation Models With Dynamic Shear Stress In Vitro Experiments

2012 ◽  
Author(s):  
Jawaad Sheriff ◽  
Michalis Xenos ◽  
João S. Soares ◽  
Jolyon Jesty ◽  
Danny Bluestein
Keyword(s):  
Platelet Activation ◽  
Heart Valves ◽  
Ventricular Assist Devices ◽  
Prosthetic Heart Valves ◽  
Shear Stresses ◽  
Ventricular Assist ◽  
Relative Paucity ◽  
Valvular Diseases ◽  
End Stage

Blood recirculating devices, which include ventricular assist devices and prosthetic heart valves, are necessary for some patients suffering from end-stage heart failure and valvular diseases. However, disturbed flow patterns in these devices cause shear-induced platelet activation and aggregation. Thromboembolic complications resulting from this platelet behavior necessitates lifelong anticoagulant therapy for patients implanted with such devices. In addition, blood recirculating device manufacturers mostly test and optimize their products for hemolysis, which occurs at shear stresses ten-fold higher than required for platelet activation. The relative paucity of optimization for flow-induced thrombogenicity is further exacerbated by the fact that there are few predictive shear-induced platelet activation models.

Reduction of Flow-Induced Blood Damage in Bileaflet Mechanical Heart Valves Through Passive Flow Control

2008 ◽  
Author(s):  
David W. Murphy ◽  
Lakshmi P. Dasi ◽  
Ari Glezer ◽  
Ajit P. Yoganathan
Keyword(s):  
Shear Stress ◽  
Platelet Activation ◽  
Heart Valves ◽  
Vortex Generators ◽  
Mechanical Heart Valves ◽  
Shear Stresses ◽  
Valve Closure ◽  
Passive Flow Control ◽  
Blood Damage ◽  
Passive Flow

Bileaflet mechanical heart valves (BMHVs), though a life-saving device in treating heart valve disease, are often associated with several complications including a high risk of hemolysis, platelet activation, and thromboembolism. To address this risk, patients must undergo prophylactic anticoagulation therapy. One likely cause of this hyper-coagulative state is the nonphysiologic levels of stress experienced by the erythrocytes and platelets flowing through the BMHVs. Research has shown that the combination of shear stress magnitude and exposure time found in the highly transient leakage jet emanating from the b-datum gap during valve closure is sufficient to cause hemolysis and platelet activation [1–3]. Reducing the shear stresses experienced by the blood flowing through the b-datum gap during valve closure may therefore reduce the prevalence of valve-related blood damage. Such shear stress reduction could be achieved by passive flow control, in particular vortex generators, incorporated onto the BMHV leaflet surface. Vortex generators have been used to control shear flows in various aerodynamic applications, and it is thus thought that their application to mechanical heart valve leaflet surfaces may reduce shear stresses by creating streamwise vortices that will serve to dissipate the regurgitant jet originating from the b-datum gap at the time of valve closure.

scholarly journals On the Use of the Platelet Activity State Assay for the In Vitro Quantification of Platelet Activation in Blood Recirculating Devices for Extracorporeal Circulation

2016 ◽  
Vol 40 (10) ◽  
pp. 971-980 ◽  
Author(s):  
Filippo Consolo ◽  
Lorenzo Valerio ◽  
Stefano Brizzola ◽  
Paolo Rota ◽  
Giulia Marazzato ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Extracorporeal Circulation ◽  
Platelet Activity ◽  
Activity State

scholarly journals Heparin is more effective than apixaban in inhibiting in vitro contact activated coagulation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M.M Engelen ◽  
C Van Laer ◽  
M Jacquemin ◽  
C Vandenbriele ◽  
K Peerlinck ◽  
...  
Keyword(s):  
Thrombin Generation ◽  
Heart Valves ◽  
Thrombus Formation ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Mechanical Heart Valves ◽  
Contact Activation

Abstract Introduction Contact of blood with artificial surfaces such as mechanical support devices, catheters, and mechanical heart valves activates the contact activation (CA) pathway of coagulation. Furthermore, recent animal data and clinical studies suggest a more important contribution of CA in pathological thrombus formation in other cardiovascular diseases. Direct oral anticoagulants (DOACs) are recommended as first-line treatment in most patients who require long-term anticoagulation. However, because DOACs directly inhibit a single downstream coagulation factor (thrombin (fXIIa) or factor Xa (fXa)), it has been suggested that their efficacy could be reduced in the presence of strong activation of the CA pathway as compared to anticoagulants that target multiple, more upstream located coagulation factors. Purpose To compare the efficacy of a DOAC (apixaban) and heparin to suppress thrombin generation in the presence of strong CA pathway activation. Methods Pooled platelet-poor plasma was spiked with either apixaban (dissolved in DMSO and PBS) or unfractionated heparin to achieve therapeutic plasma levels. SynthASil, a commercially available mixture of phospholipids and silica, was used to stimulate the CA pathway in two different dilutions (1–80 and 5–80). Downstream coagulation was accessed by Thrombin Generation Test using Thrombinoscope by Stago and associated Thrombin Calibrator (activity 640 nM). The endogenous thrombin potential (area under the thrombin generation curve; ETP), peak thrombin generation (PTG), time to peak (ttPeak) and time to start (ttStart) were accessed. Results With decreasing concentrations of apixaban, stimulation with the lower dose SynthASil reveals an increasing ETP and PTG. As expected, ttPeak and ttStart decreased. Even supratherapeutic levels of apixaban (i.e. 1120 ng/mL) could not inhibit thrombin from being generated, in striking contrast with UFH where no thrombin was formed. Using a five times higher dose of SynthASil showed comparable ETP for all concentrations of apixaban, allocated around the control value. PTG, however, slightly increased with decreasing concentrations of apixaban. ttPeak and ttStart slightly decreased. Except for the subtherapeutic UFH concentration of 0,114 IU/mL, no thrombin was generated with UFH. Conclusion UFH is more effective in inhibiting downstream thrombin generation compared to apixaban as a response to activation of the CA pathway in vitro. These findings could help explain why direct inhibitors were not able to show non-inferiority in patients with mechanical heart valves and support the development of specific CA pathway inhibitors for patients with conditions that activate the CA pathway. Thrombin generation curves Funding Acknowledgement Type of funding source: None

In-vitro characterization of flow through mechanical heart valves

2006 ◽  
Vol 39 ◽  
pp. S306 ◽  
Author(s):  
L.P. Dasi ◽  
H. Simon ◽  
L. Ge ◽  
F. Sotiropoulos ◽  
A. Yoganathan
Keyword(s):  
Heart Valves ◽  
Mechanical Heart Valves ◽  
In Vitro Characterization ◽  
Flow Through

Argatroban and bivalirudin compared to unfractionated heparin in preventing thrombus formation on mechanical heart valves

2009 ◽  
Vol 101 (06) ◽  
pp. 1163-1169 ◽  
Author(s):  
Torsten Linde ◽  
Thomas Michel ◽  
Kathrin Hamilton ◽  
Ulrich Steinseifer ◽  
Ivar Friedrich ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Unfractionated Heparin ◽  
Continuous Infusion ◽  
Valve Replacement ◽  
Heart Valves ◽  
Thrombus Formation ◽  
Mechanical Heart Valve ◽  
Mechanical Heart Valves ◽  
Valve Prostheses

SummaryPrevention of valve thrombosis in patients after prosthetic mechanical heart valve replacement and heparin-induced thrombocytopenia (HIT) is still an open issue. The aim of the present in-vitro study was to investigate the efficacy of argatroban and bivalirudin in comparison to unfractionated heparin (UFH) in preventing thrombus formation on mechanical heart valves. Blood (230 ml) from healthy young male volunteers was anticoagulated either by UFH, argatroban bolus, argatroban bolus plus continuous infusion, bivalirudin bolus, or bivalirudin bolus plus continuous infusion. Valve prostheses were placed in a newly developed in-vitro thrombosis tester and exposed to the anticoagulated blood samples. To quantify the thrombi, electron microscopy was performed, and each valve was weighed before and after the experiment. Mean thrombus weight in group 1 (UFH) was 117 + 93 mg, in group 2 (argatroban bolus) 722 + 428 mg, in group 3 (bivalirudin bolus) 758 + 323 mg, in group 4 (argatroban bolus plus continuous infusion) 162 + 98 mg, and in group 5 (bivalirudin bolus plus continuous infusion) 166 + 141 mg (p-value <0.001). Electron microscopy showed increased rates of thrombus formation in groups 2 and 3. Argatroban and bivalirudin were as effective as UFH in preventing thrombus formation on valve prostheses in our in-vitro investigation when they were administered continuously. We hypothesise that continuous infusion of argatroban or bivalirudin are optimal treatment options for patients with HIT after mechanical heart valve replacement for adapting oral to parenteral anticoagulation or vice versa.

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