Device-Induced Hemostatic Disorders in Mechanically Assisted Circulation

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Abstract

Mechanically assisted circulation (MAC) sustains the blood circulation in the body of a patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) or on ventricular assistance with a ventricular assist device (VAD) or on extracorporeal membrane oxygenation (ECMO) with a pump-oxygenator system. While MAC provides short-term (days to weeks) support and long-term (months to years) for the heart and/or lungs, the blood is inevitably exposed to non-physiological shear stress (NPSS) due to mechanical pumping action and in contact with artificial surfaces. NPSS is well known to cause blood damage and functional alterations of blood cells. In this review, we discussed shear-induced platelet adhesion, platelet aggregation, platelet receptor shedding, and platelet apoptosis, shear-induced acquired von Willebrand syndrome (AVWS), shear-induced hemolysis and microparticle formation during MAC. These alterations are associated with perioperative bleeding and thrombotic events, morbidity and mortality, and quality of life in MCS patients. Understanding the mechanism of shear-induce hemostatic disorders will help us develop low-shear-stress devices and select more effective treatments for better clinical outcomes.

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The lung is a site of platelet biogenesis and a reservoir for hematopoietic progenitors

Emma Lefrancais, Guadalupe Ortiz-Muñoz, Axelle Caudrillier … (2017)

Platelets are critical for hemostasis, thrombosis, and inflammatory responses 1,2 , yet the events leading to mature platelet production remain incompletely understood 3 . The bone marrow (BM) is proposed to be a major site of platelet production although indirect evidence points towards a potential pulmonary contribution to platelet biogenesis 4-7 . By directly imaging the lung microcirculation in mice 8 , we discovered that a large number of megakaryocytes (MKs) circulate through the lungs where they dynamically release platelets. MKs releasing platelets in the lung are of extrapulmonary origin, such as the BM, where we observed large MKs migrating out of the BM space. The lung contribution to platelet biogenesis is substantial with approximately 50% of total platelet production or 10 million platelets per hour. Furthermore, we identified populations of mature and immature MKs along with hematopoietic progenitors that reside in the extravascular spaces of the lung. Under conditions of thrombocytopenia and relative stem cell deficiency in the BM 9 , these progenitors can migrate out of the lung, repopulate the BM, completely reconstitute blood platelet counts, and contribute to multiple hematopoietic lineages. These results position the lung as a primary site of terminal platelet production and an organ with considerable hematopoietic potential.

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The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease.

Russell Rother, Leonard Bell, Peter Hillmen … (2005)

The efficient sequestration of hemoglobin by the red blood cell membrane and the presence of multiple hemoglobin clearance mechanisms suggest a critical need to prevent the buildup of this molecule in the plasma. A growing list of clinical manifestations attributed to hemoglobin release in a variety of acquired and iatrogenic hemolytic disorders suggests that hemolysis and hemoglobinemia should be considered as a novel mechanism of human disease. Pertinent scientific literature databases and references were searched through October 2004 using terms that encompassed various aspects of hemolysis, hemoglobin preparations, clinical symptoms associated with plasma hemoglobin, nitric oxide in hemolysis, anemia, pulmonary hypertension, paroxysmal nocturnal hemoglobinuria, and sickle-cell disease. Hemoglobin is released into the plasma from the erythrocyte during intravascular hemolysis in hereditary, acquired, and iatrogenic hemolytic conditions. When the capacity of protective hemoglobin-scavenging mechanisms has been saturated, levels of cell-free hemoglobin increase in the plasma, resulting in the consumption of nitric oxide and clinical sequelae. Nitric oxide plays a major role in vascular homeostasis and has been shown to be a critical regulator of basal and stress-mediated smooth muscle relaxation and vasomotor tone, endothelial adhesion molecule expression, and platelet activation and aggregation. Thus, clinical consequences of excessive cell-free plasma hemoglobin levels during intravascular hemolysis or the administration of hemoglobin preparations include dystonias involving the gastrointestinal, cardiovascular, pulmonary, and urogenital systems, as well as clotting disorders. Many of the clinical sequelae of intravascular hemolysis in a prototypic hemolytic disease, paroxysmal nocturnal hemoglobinuria, are readily explained by hemoglobin-mediated nitric oxide scavenging. A growing body of evidence supports the existence of a novel mechanism of human disease, namely, hemolysis-associated smooth muscle dystonia, vasculopathy, and endothelial dysfunction.

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Platelet biology and functions: new concepts and clinical perspectives

Paola van der Meijden, Johan Heemskerk (2018)

Platelets - blood cells continuously produced from megakaryocytes mainly in the bone marrow - are implicated not only in haemostasis and arterial thrombosis, but also in other physiological and pathophysiological processes. This Review describes current evidence for the heterogeneity in platelet structure, age, and activation properties, with consequences for a diversity of platelet functions. Signalling processes of platelet populations involved in thrombus formation with ongoing coagulation are well understood. Genetic approaches have provided information on multiple genes related to normal haemostasis, such as those encoding receptors and signalling or secretory proteins, that determine platelet count and/or responsiveness. As highly responsive and secretory cells, platelets can alter the environment through the release of growth factors, chemokines, coagulant factors, RNA species, and extracellular vesicles. Conversely, platelets will also adapt to their environment. In disease states, platelets can be positively primed to reach a pre-activated condition. At the inflamed vessel wall, platelets interact with leukocytes and the coagulation system, interactions mediating thromboinflammation. With current antiplatelet therapies invariably causing bleeding as an undesired adverse effect, novel therapies can be more beneficial if directed against specific platelet responses, populations, interactions, or priming conditions. On the basis of these novel concepts and processes, we discuss several initiatives to target platelets therapeutically.

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Author and article information

Journal

Journal ID (nlm-ta): Clin Appl Thromb Hemost

Journal ID (iso-abbrev): Clin Appl Thromb Hemost

Journal ID (publisher-id): CAT

Journal ID (hwp): spcat

Title: Clinical and Applied Thrombosis/Hemostasis

Publisher: SAGE Publications (Sage CA: Los Angeles, CA )

ISSN (Print): 1076-0296

ISSN (Electronic): 1938-2723

Publication date (Electronic): 11 February 2021

Publication date Collection: Jan-Dec 2021

Volume: 27

Electronic Location Identifier: 1076029620982374

Affiliations

[1 ]Department of Surgery, Ringgold 12264, University of Maryland School of Medicine; , Baltimore, MD, USA

[2 ]Fischell Department of Bioengineering, A. James Clark School of Engineering, University of Maryland, College Park, MD, USA

Author notes

[*]Zhongjun J. Wu, Department of Surgery, University of Maryland School of Medicine, 10 South Pine Street, MSTF 436, Baltimore, MD 21201, USA. Email: zwu@ 123456som.umaryland.edu

Author information

Shigang Wang https://orcid.org/0000-0002-5229-3330

Article

Publisher ID: 10.1177_1076029620982374

DOI: 10.1177/1076029620982374

PMC ID: 7883139

PubMed ID: 33571008

SO-VID: 29f0d844-4b10-4de7-8a1a-35c2714d6b10

License:

This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

History

Date received : 14 October 2020

Date revision received : 21 November 2020

Date accepted : 01 December 2020

Funding

Funded by: National Heart, Lung, and Blood Institute, FundRef https://doi.org/10.13039/100000050;

Award ID: R01HL118372, R01HL124170, and R01HL141817

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cover-date January-December 2021

typesetter ts3

Keywords: cardiopulmonary bypass,extracorporeal membrane oxygenation,ventricular assist device,mechanical shear stress,hemostatic disorder

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Keywords: cardiopulmonary bypass, extracorporeal membrane oxygenation, ventricular assist device, mechanical shear stress, hemostatic disorder

Device-Induced Hemostatic Disorders in Mechanically Assisted Circulation

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Most cited references 170

The lung is a site of platelet biogenesis and a reservoir for hematopoietic progenitors

The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease.

Platelet biology and functions: new concepts and clinical perspectives

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