Platelet-Derived Microparticles Generated by Neonatal Extracorporeal Membrane Oxygenation Systems

Meyer, Andrew; Gelfond, Jonathan; Wiles, Andrew A.; Freishtat, Robert J.; Rais-Bahrami, Khodayar

doi:10.1097/mat.0000000000000164

Cited by 32 publications

(32 citation statements)

References 33 publications

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“…This is the first publication to document the effect of low, nominal, and high ex vivo ECMO flow on human platelets, leukocytes, and EVs. Previous laboratory studies documented that ECMO increases prothrombotic cells and EVs but were limited to circuits without an oxygenator, with component blood products that exclude platelets and leukocytes, or used animal blood . Case series documented increased concentrations of activated platelets, leukocytes, and EVs collected at the end of coronary bypass surgery or during support with a left ventricular assist device .…”

Section: Discussionmentioning

confidence: 99%

“… Extracellular vesicles, also known as microparticles, are small (0.3‐1 micron) cell‐derived membrane vesicles that can contribute to clot formation by the initiation and propagation of clotting without exposure to an artificial surface . Our in vitro studies documented the release of platelet‐derived EVs in a neonatal ECMO model using porcine whole blood . However, the effect of ECMO pump flow rate on the generation of prothrombotic cells, EV, and thrombin generation in human blood remains to be established.…”

Section: Introductionmentioning

confidence: 91%

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Effect of blood flow on platelets, leukocytes, and extracellular vesicles in thrombosis of simulated neonatal extracorporeal circulation

Meyer

Rishmawi

Kamucheka

et al. 2020

Journal of Thrombosis and Haemostasis

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Background: Extracorporeal membrane oxygenation (ECMO) has frequent and sometimes lethal thrombotic complications. The role that activated platelets, leukocytes, and small (0.3-micron to 1-micron) extracellular vesicles (EVs) play in ECMO thrombosis is not well understood.Objectives: To test the effect of blood flow rate on the generation of activated platelets, leukocytes, and EVs in a simulated neonatal ECMO circuit using heparinized human whole blood. Methods: Simulated neonatal roller pump circuits circulated whole blood at low, nominal, and high flow rates (0.3, 0.5, and 0.7 L/min) for 6 h. Coagulopathy was defined by thromboelastography (TEG), STA ® -procoagulant phospholipid clot time (STA ®-Procoag-PPL), and calibrated automated thrombogram. High-resolution flow cytometry measured the cellular expression of prothrombotic phospholipids and proteins on platelets, leukocytes, and EV. Results: Despite heparinization, occlusive thrombosis halted flow in two of five circuits at 0.3 L/min and three of five circuits at 0.7 L/min. None of the five circuits at 0.5 L/min exhibited occlusive thrombosis. Phosphatidylserine (PS)-positive platelets and EVs increased at all flow rates more than blood under static conditions (P < .0002). Tissue factor (TF)-positive leukocytes and EVs increased only in low-flow and high-flow circuits (P < .0001). Tissue factor pathway inhibitor (TFPI), at 50 times more than the concentration in healthy adults, failed to suppress thrombin initiation in low-flow and high-flow circuits.Conclusions: This in vitro study informs ECMO specialists to avoid low and high blood flow that increases TF expression on leukocytes and EVs, which likely initiate clot formation. Interventions to decrease TF generated by ECMO may be an effective approach to decrease thrombosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

Effect of blood flow on platelets, leukocytes, and extracellular vesicles in thrombosis of simulated neonatal extracorporeal circulation

Meyer

Rishmawi

Kamucheka

et al. 2020

Journal of Thrombosis and Haemostasis

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“…Similarly, we saw little evidence of ECMO-driven activation of the contact pathway, as pre-injury changes in Factors VIII, IX, and XII were inconsistent and relatively minor. Another mechanism that causes platelet activation is the shear stress from the blood pump generating increased von Willebrand factor binding to GP1b and outside-in signaling ( 39 – 41 ). Our results support this platelet-led mechanism; the shear stress of the extracorporeal pump ( 39 , 41 ) activates platelets, unfolding vWF, subsequent aggregation, and clearance ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

Low-Dose Heparin Anticoagulation During Extracorporeal Life Support for Acute Respiratory Distress Syndrome in Conscious Sheep

Prat

Meyer

Länger

et al. 2015

Shock

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Background:Over 32% of burned battlefield causalities develop trauma-induced hypoxic respiratory failure, also known as acute respiratory distress syndrome (ARDS). Recently, 9 out of 10 US combat soldiers’ survived life-threatening trauma-induced ARDS supported with extracorporeal membrane oxygenation (ECMO), a portable form of cardiopulmonary bypass. Unfortunately, the size, incidence of coagulation complications, and the need for systematic anticoagulation for traditional ECMO devices have prevented widespread use of this lifesaving technology. Therefore, a compact, mobile, ECMO system using minimal anticoagulation may be the solution to reduce ARDS in critically ill military and civilian patients.Methods:We conducted a prospective cohort laboratory investigation to evaluate the coagulation function in an ovine model of oleic acid induced ARDS supported with veno-venous ECMO. The experimental design approximated the time needed to transport from a battlefield setting to an advanced facility and compared bolus versus standard heparin anticoagulation therapy.Results:Comprehensive coagulation and hemostasis assays did not show any difference because of ECMO support over 10 h between the two groups but did show changes because of injury. Platelet count and function did decrease with support on ECMO, but there was no significant bleeding or clot formation during the entire experiment.Conclusions:A bolus heparin injection is sufficient to maintain ECMO support for up to 10 h in an ovine model of ARDS. With a reduced need for systematic anticoagulation, ECMO use for battlefield trauma could reduce significant morbidity and mortality from ventilator-induced lung injury and ARDS. Future studies will investigate the mechanisms and therapies to support patients for longer periods on ECMO without coagulation complications.Level of Evidence:V—therapeutic animal experiment.

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“…This is not associated with significant activation of the endothelium [126], but may be due to the release of platelet granules [152]. Furthermore, this time-dependent platelet activation is also accompanied by platelet receptor shedding and the release of platelet microparticles (PMPs) [153]. These are small cell-derived particles, typically 0.1-1 μm in size, that are produced from activated platelets in situations of shear stress [154].…”

Section: Platelet Dysfunction During Ecmomentioning

confidence: 99%

“…These are small cell-derived particles, typically 0.1-1 μm in size, that are produced from activated platelets in situations of shear stress [154]. While these PMPs can present a prothrombotic surface, it is not clear whether they are a major contributor to the prothrombotic phenotype or to the pathogenesis of ECMO-associated coagulopathy [153].…”

Section: Platelet Dysfunction During Ecmomentioning

confidence: 99%

Platelets in the Newborn

Esiaba¹,

Mousselli²,

Faison³

et al. 2019

Neonatal Medicine

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Platelets were first described in the mid-nineteenth century. Since then, their roles were identified in hemostasis and thrombosis, inflammation, leukocyte interactions, angiogenesis, and cancer growth. But there is little information about such platelet functions in the newborn. Several studies highlighted some platelet differences between newborns and adults. Yet, in spite of these differences, healthy newborns appear to be adequately protected. A number of factors, however, were reported to negatively affect neonatal platelets. These include maternal hypertensive disorders or infections, neonatal asphyxia or respiratory distress, therapies such as ampicillin or indomethacin, and treatment modalities such as ventilators, nitric oxide, or extracorporeal membrane oxygenation (ECMO). Their effects on newborn platelets are usually transitory, lasting from several hours to a few days or weeks. If these effects are well characterized, they could serve as reporters for diagnosis and monitoring during therapy. Careful studies of neonatal platelets are needed to improve the understanding of basic physiology and pathophysiology in this cohort and to identify possible targets for intervention and therapy.

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Platelet-Derived Microparticles Generated by Neonatal Extracorporeal Membrane Oxygenation Systems

Cited by 32 publications

References 33 publications

Effect of blood flow on platelets, leukocytes, and extracellular vesicles in thrombosis of simulated neonatal extracorporeal circulation

Effect of blood flow on platelets, leukocytes, and extracellular vesicles in thrombosis of simulated neonatal extracorporeal circulation

Low-Dose Heparin Anticoagulation During Extracorporeal Life Support for Acute Respiratory Distress Syndrome in Conscious Sheep

Platelets in the Newborn

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