Hemolysis in Pediatric Patients Receiving Centrifugal-Pump Extracorporeal Membrane Oxygenation

Lou, Song; MacLaren, Graeme; Best, Derek; Delzoppo, Carmel; Butt, Warwick

doi:10.1097/ccm.0000000000000128

Cited by 126 publications

(153 citation statements)

References 18 publications

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“…Similarly, despite improved management of anticoagulation and transfusion in patients on ECMO, thrombosis is a main cause of mortality and morbidity (Oliver, 2009 (Lou et al, 2014). Furthermore, there is an association between haemolysis and circuit thrombosis (Zangrillo et al, 2013).…”

Section: Mechanical Circulatory Supportmentioning

confidence: 99%

New perspectives on the thrombotic complications of haemolysis

L’Acqua

Hod

2014

Br J Haematol

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SummaryMany clinical settings are associated with haemolysis, from rare conditions, such as paroxysmal nocturnal haemoglobinuria, to common interventions, such as mechanical circulatory support and blood transfusion. The toxic effects of circulating free haemoglobin, haem, and iron are becoming increasingly understood and include an increased risk of thrombotic complications. This review summarizes the epidemiological evidence for an association between haemolysis and thrombosis and explores potential underlying mechanisms. New insights into the role haem plays in inflammatory signalling and in generating neutrophil extracellular traps (NETs) may provide useful strategies for managing pathological states associated with severe haemolysis. A better understanding of the toxic effects of haemolysis will result in better therapies to prevent the side effect of thrombosis.

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Section: Mechanical Circulatory Supportmentioning

confidence: 99%

New perspectives on the thrombotic complications of haemolysis

L’Acqua

Hod

2014

Br J Haematol

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“…Recent studies have shown a clear association between extracellular Hb and the development of postoperative acute kidney injury after surgery on CPB [41][42][43][44], suggesting a crucial role in the induction of inflammation and oxidative stress by Hb and its metabolites [45]. In clinical studies on paediatric and adult ECMO patients increased levels of plasma extracellular Hb are associated with increased mortality [43,46]. …”

Section: Extracorporeal Circulation and Haemolysismentioning

confidence: 99%

Pathophysiology of extracellular haemoglobin: use of animal models to translate molecular mechanisms into clinical significance

Smeds

Romantsik

Jungner

et al. 2016

ISBT Science Series

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Pathophysiology of extracellular haemoglobinuse of animal models to translate molecular mechanisms into clinical significance Smeds, Emanuel; Romantsik, Olga; Jungner, Åsa; Erlandsson, Lena; Gram, Magnus General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. AbstractThe blood's major gas-exchange is carried out by haemoglobin, a heme-protein that binds iron and oxygen and can have potentially dangerous side effects due to redox reactions.Haemoglobin is a very abundant molecule with a concentration of 150 g/L in whole blood, resulting in almost one kg haemoglobin in an adult human body. Normal turn-over of red blood cells results in significant haemoglobin release, and pathological conditions that involve haemolysis can lead to massive haemoglobin levels. To control for the potential threat of extracellular haemoglobin, several protective defence systems have evolved.Many pathological conditions, diseases as well as iatrogenic conditions, such as infusion of haemoglobin-based oxygen carriers, cerebral intraventricular haemorrhage, extracorporeal circulation and the pregnancy complication preeclampsia, involve abnormal levels of haemolysis and extracellular haemoglobin. Although quite different aetiology, the haemoglobin-induced damage often cause similar clinical sequelae and symptoms. Here we will give an overview of the pathophysiological mechanisms of extracellular haemoglobin and its metabolites. Furthermore, we will highlight the use of animal models in advancing the understanding of these mechanisms and discuss how to utilize the knowledge in the development of new and better pharmaceutical therapies.

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“…1 Increasing incidence of hemolysis and thrombosis is associated with morbidity and mortality in patients on extracorporeal membrane oxygenation (ECMO). 2 Prevention of circuit clotting in ECMO can improve clinical outcome.…”

Section: Introductionmentioning

confidence: 99%

Free hemoglobin increases von Willebrand factor–mediated platelet adhesion in vitro: implications for circulatory devices

Teruya

Guchhait

et al. 2015

Blood

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• Extracellular Hb alters the GPIba-VWF interaction.Intravascular hemolysis occurs in patients on extracorporeal membrane oxygenation. High levels of free acellular adult hemoglobin (free HbA) are associated with clotting in this mechanical device that can result in thrombotic complications. Adsorption of fibrinogen onto the surface of biomaterial correlates with platelet adhesion, which is mediated by von Willebrand factor (VWF). Because free Hb interacts with VWF, we studied the effect of hemoglobin (Hb) on platelet adhesion to fibrin(ogen) under conditions of different hydrodynamic forces. This effect was investigated using purified human HbA and fibrinogen, extracellular matrix, collagen, or purified plasma VWF as surface-coated substrates to examine flow-dependent platelet adhesion. Antibodies and VWF-deficient plasma were also used. Free Hb ( ‡50 mg/dL) effectively augmented platelet adhesion, and microthrombi formation on fibrin(ogen), extracellular matrix, and collagen at high shear stress. The effect of free Hb was effectively blocked by anti-glycoprotein Iba (GPIba) antibodies or depletion of VWF. Unexpectedly, free Hb also promoted firm platelet adhesion and stable microthrombi on VWF. Lastly, we determined that Hb interacts directly with the A1 domain. This study is the first to demonstrate that extracellular Hb directly affects the GPIba-VWF interaction in thrombosis, and describes another mechanism by which hemolysis is connected to thrombotic events. (Blood. 2015; 126(20):2338-2341 IntroductionThe excessive release of hemoglobin (Hb) from erythrocytes into the circulation of patients on mechanical circulatory support devices is a well-recognized major clinical complication.1 Increasing incidence of hemolysis and thrombosis is associated with morbidity and mortality in patients on extracorporeal membrane oxygenation (ECMO).2 Prevention of circuit clotting in ECMO can improve clinical outcome.von Willebrand factor (VWF) is a multimeric plasma glycoprotein that mediates platelet adhesion, activation, and aggregation under high flow conditions. 3-7 Plasma VWF mediates platelet adhesion to surfaces coated with fibrin(ogen), 8,9 which is adsorbed onto surfaces of many materials used in biomedical instruments, including ECMO.10,11 Previously, we reported that free Hb interacts with the A2 domain of VWF 12 and, moreover, we and many others have described that the A2 domain regulates the binding of its neighboring A1 domain in VWF to platelet receptor glycoprotein Iba (GPIba).13-15 Thus, in this study, we examined the effect of the free Hb-VWF interaction on mediating platelet adhesion to immobilized fibrin(ogen) at high shear stress; a mechanism not previously investigated. Study design ReagentsPurified Hb and plasma VWF were obtained using established methods.13,16 Human collagen type III was purchased from Advanced BioMatrix, human fibrinogen from Calbiochem, and extracellular matrix (ECM) from Sigma-Aldrich. Anti-GPIba antibody 6D1 was a gift from Dr Barry Coller (The Rockefeller University, New Yor...

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Hemolysis in Pediatric Patients Receiving Centrifugal-Pump Extracorporeal Membrane Oxygenation

Cited by 126 publications

References 18 publications

New perspectives on the thrombotic complications of haemolysis

New perspectives on the thrombotic complications of haemolysis

Pathophysiology of extracellular haemoglobin: use of animal models to translate molecular mechanisms into clinical significance

Free hemoglobin increases von Willebrand factor–mediated platelet adhesion in vitro: implications for circulatory devices

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