Enhanced microparticles in ventricular assist device patients predict platelet, leukocyte and endothelial cell activation

Diehl, Philipp; Aleker, Miriam; Helbing, Thomas; Sossong, Verena; Beyersdorf, Friedhelm; Olschewski, Manfred; Bode, Christoph; Moser, Martin

doi:10.1510/icvts.2010.232603

Cited by 83 publications

(85 citation statements)

References 15 publications

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“…The MPs have been suggested to be involved in thrombus formation, through binding of platelets to activated endothelium and through activation of the intrinsic coagulation pathway via Factor XII exposure to negatively charged membrane particles (10,23,24). Shear stress has been suggested to mechanistically underpin MP release as demonstrated by increased platelet-derived MPs (PMPs) in patients implanted with prosthetic heart valves who typically experience high levels of shear, and whose elevated PMPs are the suspected cause of cerebrovascular events.…”

Section: Discussionmentioning

confidence: 99%

The CentriMag Centrifugal Blood Pump as a Benchmark for In Vitro Testing of Hemocompatibility in Implantable Ventricular Assist Devices

et al. 2014

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Implantable ventricular assist devices (VADs) have proven efficient in advanced heart failure patients as a bridge-to-transplant or destination therapy. However, VAD usage often leads to infection, bleeding, and thrombosis, side effects attributable to the damage to blood cells and plasma proteins. Measuring hemolysis alone does not provide sufficient information to understand total blood damage, and research exploring the impact of currently available pumps on a wider range of blood cell types and plasma proteins such as von Willebrand factor (vWF) is required to further our understanding of safer pump design. The extracorporeal CentriMag (Thoratec Corporation, Pleasanton, CA, USA) has a hemolysis profile within published standards of normalized index of hemolysis levels of less than 0.01 g/100 L at 100 mm Hg but the effect on leukocytes, vWF multimers, and platelets is unknown. Here, the CentriMag was tested using bovine blood (n = 15) under constant hemodynamic conditions in comparison with a static control for total blood cell counts, hemolysis, leukocyte death, vWF multimers, microparticles, platelet activation, and apoptosis. The CentriMag decreased the levels of healthy leukocytes (P < 0.006), induced leukocyte microparticles (P < 10−5), and the level of high molecular weight of vWF multimers was significantly reduced in the CentriMag (P < 10−5) all compared with the static treatment after 6 h in vitro testing. Despite the leukocyte damage, microparticle formation, and cleavage of vWF multimers, these results show that the CentriMag is a hemocompatible pump which could be used as a standard in blood damage assays to inform the design of new implantable blood pumps.

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Section: Discussionmentioning

confidence: 99%

The CentriMag Centrifugal Blood Pump as a Benchmark for In Vitro Testing of Hemocompatibility in Implantable Ventricular Assist Devices

et al. 2014

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“…Exclusion criteria for participation were acute infectious disease, age below 18 years and anaemia ( Table 2). Data of PH patients were compared to a historical control group of 16 control patients [12]. Control patients were admitted with chest pain to the Department of Cardiology and did not suffer from PH or diseases which are known to be associated with MP release.…”

Section: Study Design and Patient Characteristicsmentioning

confidence: 99%

“…This induces binding of different plasmatic coagulation factors, as well as tissue factor or selectins on the MP surface promoting vascular inflammation and coagulation, which is why MP have strong inflammatory and pro-coagulatory characteristics [9,10]. Hence, they can be found in a wide range of cardiovascular diseases [11,12].…”

Section: Introductionmentioning

confidence: 99%

Increased platelet, leukocyte and endothelial microparticles predict enhanced coagulation and vascular inflammation in pulmonary hypertension

Diehl

Aleker

Helbing

et al. 2010

J Thromb Thrombolysis

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Pulmonary hypertension (PH) is associated with platelet activation, vascular inflammation and endothelial dysfunction leading to often life threatening thrombo-embolic complications. Microparticles (MPs) are cell vesicles with strong coagulatory and inflammatory effects being released during cell activation and apoptosis. As there are currently no established surrogate markers predicting platelet activation and pro-coagulation in PH patients, the aim of the study was to analyze different pro-coagulatory MP populations that might be related to thrombo-embolic complications in PH patients. Circulating MPs from platelet- (PMP, CD31(+)/61(+)), leukocyte- (LMP, CD11b(+)) and endothelial- (EMP, CD62E(+)) origin were measured by flow cytometry in 19 PH patients and were compared to 16 controls. PH patients had increased levels of PMP (PH vs. control 1,016 ± 201 vs. 527 ± 59 counts per min [cpm], P = 0.032), LMP (PH vs. control 31 ± 3 cpm vs. 18 ± 2 cpm, P = 0.001) and EMP (PH vs. control 99 ± 14 cpm vs. 46 ± 6 cpm, P = 0.001). Furthermore, PMP correlated to LMP (PMP vs. LMP: r = 0.75, P < 0.001) and LMP correlated to EMP levels (LMP vs. EMP, r = 0.74, P < 0.001) indicating a functional interaction between the different types of MP. In comparison to non-embolic PH patients, patients with a thrombo-embolic PH suffered from enhanced endothelial cell dysfunction as represented by significantly increased EMP levels (thrombo-embolic PH vs. non-embolic PH 137 ± 27 vs. 72 ± 10, P = 0.02). PH patients have increased levels of platelet-, leukocyte- and endothelial MP indicating an increased vascular pro-coagulation and inflammation which might be related to thrombo-embolic complications as well as PH progression.

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“…The deposition of fibrinogen to the artificial surfaces provides ample binding and activation signals to the platelet through their GIIb/IIIa receptors [85,86]. Further, the altered shear stress environments are also known to activate platelets [87,88] to form aggregates with other cells, including monocytes and other platelets via von Willebrand factor (vWF) and pselectin mechanisms under inflammatory conditions related to mechanical circulatory support devices [89,90]. Pharmacologic intervention into platelet activation and adhesion has only been recently explored in the laboratory and a few small case studies, but most studies show a potentially beneficial effect.…”

Section: Anti-platelet Agentsmentioning

confidence: 99%

ECMO Biocompatibility: Surface Coatings, Anticoagulation, and Coagulation Monitoring

Maul¹,

Massicotte²,

Wearden³

2016

Extracorporeal Membrane Oxygenation: Advances in Therapy

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The interaction between the patient and the ECMO (extracorporeal membrane oxygenation) circuit initiates a significant coagulation and inflammatory response due to the large surface area of foreign material contained within the circuit. This response can be blunted with the appropriate mix of biocompatible materials and anticoagulation therapy. The use of anticoagulants, in turn, requires appropriate laboratory testing to determine whether the patient is appropriately anticoagulated. Physicians must balance the risks of bleeding with the risks of thrombosis; the proper interpretation of these tests is often shrouded in mystery. It is the purpose of this chapter to help demystify the coagulation system, anticoagulants, biocompatible surfaces, and coagulation testing so that ECMO practitioners can make informed decisions about their patients and to spur coordinated efforts for future research to improve our understanding of these complex processes.

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Enhanced microparticles in ventricular assist device patients predict platelet, leukocyte and endothelial cell activation

Cited by 83 publications

References 15 publications

The CentriMag Centrifugal Blood Pump as a Benchmark for In Vitro Testing of Hemocompatibility in Implantable Ventricular Assist Devices

The CentriMag Centrifugal Blood Pump as a Benchmark for In Vitro Testing of Hemocompatibility in Implantable Ventricular Assist Devices

Increased platelet, leukocyte and endothelial microparticles predict enhanced coagulation and vascular inflammation in pulmonary hypertension

ECMO Biocompatibility: Surface Coatings, Anticoagulation, and Coagulation Monitoring

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