The interaction of thrombocytopenia, hemorrhage, and platelet transfusion in venoarterial extracorporeal membrane oxygenation: a multicenter observational study

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Abstract

Background

Thrombocytopenia, hemorrhage and platelet transfusion are common in patients supported with venoarterial extracorporeal membrane oxygenation (VA ECMO). However, current literature is limited to small single-center experiences with high degrees of heterogeneity. Therefore, we aimed to ascertain in a multicenter study the course and occurrence rate of thrombocytopenia, and to assess the association between thrombocytopenia, hemorrhage and platelet transfusion during VA ECMO.

Methods

This was a sub-study of a multicenter ( N = 16) study on transfusion practices in patients on VA ECMO, in which a retrospective cohort (Jan-2018–Jul-2019) focusing on platelets was selected. The primary outcome was thrombocytopenia during VA ECMO, defined as mild (100–150·10 ⁹/L), moderate (50–100·10 ⁹/L) and severe (< 50·10 ⁹/L). Secondary outcomes included the occurrence rate of platelet transfusion, and the association between thrombocytopenia, hemorrhage and platelet transfusion, assessed through mixed-effect models.

Results

Of the 419 patients included, median platelet count at admission was 179·10 ⁹/L. During VA ECMO, almost all ( N = 398, 95%) patients developed a thrombocytopenia, of which a significant part severe ( N = 179, 45%). One or more platelet transfusions were administered in 226 patients (54%), whereas 207 patients (49%) suffered a hemorrhagic event during VA ECMO. In non-bleeding patients, still one in three patients received a platelet transfusion. The strongest association to receive a platelet transfusion was found in the presence of severe thrombocytopenia (adjusted OR 31.8, 95% CI 17.9–56.5). After including an interaction term of hemorrhage and thrombocytopenia, this even increased up to an OR of 110 (95% CI 34–360).

Conclusions

Thrombocytopenia has a higher occurrence than is currently recognized. Severe thrombocytopenia is strongly associated with platelet transfusion. Future studies should focus on the etiology of severe thrombocytopenia during ECMO, as well as identifying indications and platelet thresholds for transfusion in the absence of bleeding.

Trial registration: This study was registered at the Netherlands Trial Registry at February 26th, 2020 with number NL8413 and can currently be found at https://trialsearch.who.int/Trial2.aspx?TrialID=NL8413.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13054-023-04612-5.

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Most cited references 27

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The inflammatory response to extracorporeal membrane oxygenation (ECMO): a review of the pathophysiology

Jonathan Millar, Jonathon P Fanning, Charles Mcdonald … (2016)

Extracorporeal membrane oxygenation (ECMO) is a technology capable of providing short-term mechanical support to the heart, lungs or both. Over the last decade, the number of centres offering ECMO has grown rapidly. At the same time, the indications for its use have also been broadened. In part, this trend has been supported by advances in circuit design and in cannulation techniques. Despite the widespread adoption of extracorporeal life support techniques, the use of ECMO remains associated with significant morbidity and mortality. A complication witnessed during ECMO is the inflammatory response to extracorporeal circulation. This reaction shares similarities with the systemic inflammatory response syndrome (SIRS) and has been well-documented in relation to cardiopulmonary bypass. The exposure of a patient’s blood to the non-endothelialised surface of the ECMO circuit results in the widespread activation of the innate immune system; if unchecked this may result in inflammation and organ injury. Here, we review the pathophysiology of the inflammatory response to ECMO, highlighting the complex interactions between arms of the innate immune response, the endothelium and coagulation. An understanding of the processes involved may guide the design of therapies and strategies aimed at ameliorating inflammation during ECMO. Likewise, an appreciation of the potentially deleterious inflammatory effects of ECMO may assist those weighing the risks and benefits of therapy.

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Platelet transfusion: a clinical practice guideline from the AABB.

M Kaufman, Benjamin Djulbegovic, Terry Gernsheimer … (2015)

The AABB (formerly, the American Association of Blood Banks) developed this guideline on appropriate use of platelet transfusion in adult patients.

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Factors associated with outcomes of patients on extracorporeal membrane oxygenation support: a 5-year cohort study

Cecile Aubron, Allen Cheng, David Pilcher … (2013)

Introduction Mortality of patients on extracorporeal membrane oxygenation (ECMO) remains high. The objectives of this study were to assess the factors associated with outcome of patients undergoing ECMO in a large ECMO referral centre and to compare veno-arterial ECMO (VA ECMO) with veno-venous ECMO (VV ECMO). Methods We reviewed a prospectively obtained ECMO database and patients' medical records between January 2005 and June 2011. Demographic characteristics, illness severity at admission, ECMO indication, organ failure scores before ECMO and the ECMO mode and configuration were recorded. Bleeding, neurological, vascular and infectious complications that occurred on ECMO were also collected. Demographic, illness, ECMO support descriptors and complications associated with hospital mortality were analysed. Results ECMO was initiated 158 times in 151 patients. VA ECMO (66.5%) was twice as common as VV ECMO (33.5%) with a median duration significantly shorter than for VV ECMO (7 days (first and third quartiles: 5; 10 days) versus 10 days (first and third quartiles: 6; 16 days)). The most frequent complications during ECMO support were bleeding and bloodstream infections regardless of ECMO type. More than 70% of the ECMO episodes were successfully weaned in each ECMO group. The overall mortality was 37.3% (37.1% for the patients who underwent VA ECMO, and 37.7% for the patients who underwent VV ECMO). Haemorrhagic events, assessed by the total of red blood cell units received during ECMO, were associated with hospital mortality for both ECMO types. Conclusions Among neurologic, vascular, infectious and bleeding events that occurred on ECMO, bleeding was the most frequent and had a significant impact on mortality. Further studies are needed to better investigate bleeding and coagulopathy in these patients. Interventions that reduce these complications may improve outcome.

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Author and article information

Contributors

Alexander P. J. Vlaar: a.p.vlaar@amsterdamumc.nl

Journal

Journal ID (nlm-ta): Crit Care

Title: Critical Care

Publisher: BioMed Central (London )

ISSN (Print): 1364-8535

ISSN (Electronic): 1466-609X

Publication date (Electronic): 21 August 2023

Publication date PMC-release: 21 August 2023

Publication date Collection: 2023

Volume: 27

Electronic Location Identifier: 321

Affiliations

[1 ]GRID grid.509540.d, ISNI 0000 0004 6880 3010, Department of Critical Care, , Amsterdam University Medical Centers, ; Location Academic Medical Centers, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

[2 ]GRID grid.509540.d, ISNI 0000 0004 6880 3010, Department of Cardiology, , Amsterdam University Medical Centers, ; Location Academic Medical Centers, Amsterdam, The Netherlands

[3 ]GRID grid.4830.f, ISNI 0000 0004 0407 1981, Department of Critical Care, University Medical Center Groningen, , University of Groningen, ; Groningen, The Netherlands

[4 ]GRID grid.10419.3d, ISNI 0000000089452978, Adult Intensive Care Unit, , Leiden University Medical Center, ; Leiden, The Netherlands

[5 ]GRID grid.413532.2, ISNI 0000 0004 0398 8384, Adult Intensive Care Unit, , Catharina Hospital Eindhoven, ; Eindhoven, The Netherlands

[6 ]GRID grid.412966.e, ISNI 0000 0004 0480 1382, Cardiothoracic Surgery Department, Heart and Vascular Center, , Maastricht University Medical Center, and Cardiovascular Research Institute Maastricht (CARIM), ; Maastricht, The Netherlands

[7 ]GRID grid.412966.e, ISNI 0000 0004 0480 1382, Department of Cardiology, , Maastricht University Medical Center, ; Maastricht, The Netherlands

[8 ]GRID grid.5645.2, ISNI 000000040459992X, Adult Intensive Care Unit, , Erasmus University Medical Center, ; Rotterdam, The Netherlands

[9 ]GRID grid.415960.f, ISNI 0000 0004 0622 1269, Department of Intensive Care, , St. Antonius Hospital, ; Nieuwegein, The Netherlands

[10 ]GRID grid.4989.c, ISNI 0000 0001 2348 0746, Department of Intensive Care, , Université Libre de Bruxelles, Hôpital Erasme Bruxelles, ; Brussels, Belgium

[11 ]GRID grid.410569.f, ISNI 0000 0004 0626 3338, Surgical Intensive Care Unit, Department of Intensive Care Medicine, , University Hospital Leuven, ; Leuven, Belgium

[12 ]GRID grid.410569.f, ISNI 0000 0004 0626 3338, Medical Intensive Care Unit, Department of General Internal Medicine, , University Hospitals Leuven, ; Herestraat 49, 3000 Leuven, Belgium

[13 ]GRID grid.5596.f, ISNI 0000 0001 0668 7884, Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, , KU Leuven, ; Herestraat 49, 3000 Leuven, Belgium

[14 ]Department of CardioThoracic and Vascular Anesthesia and Intensive Care, AO SS Antonio e Biagio e Cesare Arrigo, Alessandria, Italy

[15 ]GRID grid.18887.3e, ISNI 0000000417581884, Department of Anesthesia and Intensive Care, , IRCCS San Raffaele Scientific Institute, ; Milan, Italy

[16 ]GRID grid.412688.1, ISNI 0000 0004 0397 9648, Department of Anesthesia and Intensive Care, , University Hospital Centre Zagreb, ; Zagreb, Croatia

[17 ]GRID grid.440209.b, ISNI 0000 0004 0501 8269, Department of Intensive Care, , OLVG, ; Amsterdam, The Netherlands

[18 ]GRID grid.7692.a, ISNI 0000000090126352, Intensive Care Center, , University Medical Center Utrecht (UMCU), ; Utrecht, The Netherlands

[19 ]GRID grid.416075.1, ISNI 0000 0004 0367 1221, Department of Critical Care, , Royal Adelaide Hospital, ; Adelaide, Australia

[20 ]GRID grid.24381.3c, ISNI 0000 0000 9241 5705, ECMO Center Karolinska, , Karolinska University Hospital, ; Stockholm, Sweden

[21 ]GRID grid.6214.1, ISNI 0000 0004 0399 8953, Cardiovascular and Respiratory Physiology, TechMed Centre, , University of Twente, ; Enschede, The Netherlands

[22 ]GRID grid.412966.e, ISNI 0000 0004 0480 1382, Department of Intensive Care, , Maastricht University Medical Center, ; Maastricht, The Netherlands

[23 ]GRID grid.7177.6, ISNI 0000000084992262, Department of Epidemiology and Data Science, Amsterdam University Medical Centre, Amsterdam Public Health, , University of Amsterdam, ; Location AMC, Amsterdam, The Netherlands

Article

Publisher ID: 4612

DOI: 10.1186/s13054-023-04612-5

PMC ID: 10441744

PubMed ID: 37605277

SO-VID: a6e03188-a44a-4be2-acca-b17d3ac12f59

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 8 June 2023

Date accepted : 14 August 2023

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ScienceOpen disciplines: Emergency medicine & Trauma

Keywords: thrombocytopenia,platelet transfusion,hemorrhage,venoarterial extracorporeal membrane oxygenation

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ScienceOpen disciplines: Emergency medicine & Trauma

Keywords: thrombocytopenia, platelet transfusion, hemorrhage, venoarterial extracorporeal membrane oxygenation

The interaction of thrombocytopenia, hemorrhage, and platelet transfusion in venoarterial extracorporeal membrane oxygenation: a multicenter observational study

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Abstract

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Conclusions

Supplementary Information

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Irish Journal of Paramedicine

Most cited references 27

The inflammatory response to extracorporeal membrane oxygenation (ECMO): a review of the pathophysiology

Platelet transfusion: a clinical practice guideline from the AABB.

Factors associated with outcomes of patients on extracorporeal membrane oxygenation support: a 5-year cohort study

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