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Intensive Care Medicine
Published in: Intensive Care Medicine 6/2020

Open Access 01-06-2020 | Thrombocytopenia | Systematic Review

Platelets and extra-corporeal membrane oxygenation in adult patients: a systematic review and meta-analysis

Authors: Federica Jiritano, Giuseppe Filiberto Serraino, Hugo ten Cate, Dario Fina, Matteo Matteucci, Pasquale Mastroroberto, Roberto Lorusso

Published in: Intensive Care Medicine | Issue 6/2020

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Abstract

Despite increasing improvement in extracorporeal membrane oxygenation (ECMO) technology and knowledge, thrombocytopenia and impaired platelet function are usual findings in ECMO patients and the underlying mechanisms are only partially elucidated. The purpose of this meta-analysis and systematic review was to thoroughly summarize and discuss the existing knowledge of platelet profile in adult ECMO population. All studies meeting the inclusion criteria (detailed data about platelet count and function) were selected, after screening literature from July 1975 to August 2019. Twenty-one studies from 1.742 abstracts were selected. The pooled prevalence of thrombocytopenia in ECMO patients was 21% (95% CI 12.9–29.0; 14 studies). Thrombocytopenia prevalence was 25.4% (95% CI 10.6–61.4; 4 studies) in veno-venous ECMO, whereas it was 23.2% (95% CI 11.8–34.5; 6 studies) in veno-arterial ECMO. Heparin-induced thrombocytopenia prevalence was 3.7% (95% CI 1.8–5.5; 12 studies). Meta-regression revealed no significant association between ECMO duration and thrombocytopenia. Platelet function impairment was described in 7 studies. Impaired aggregation was shown in 5 studies, whereas loss of platelet receptors was found in one trial, and platelet activation was described in 2 studies. Platelet transfusions were needed in up to 50% of the patients. Red blood cell transfusions were administered from 46 to 100% of the ECMO patients. Bleeding events varied from 16.6 to 50.7%, although the cause and type of haemorrhage was not consistently reported. Thrombocytopenia and platelet dysfunction are common in ECMO patients, regardless the type of ECMO mode. The underlying mechanisms are multifactorial, and understanding and management are still limited. Further research to design appropriate strategies and protocols for its monitoring, management, or prevention should be matter of thorough investigations.
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Literature
1.
Hill JD, O'Brien TG, Murray JJ et al (1972) Prolonged extracorporeal oxygenation for acute post-traumatic respiratory failure (shock-lung syndrome). Use of the Bramson membrane lung. N Engl J Med 286(12):629–634PubMedCrossRef
2.
Lindén V, Palmér K, Reinhard J et al (2000) High survival in adult patients with acute respiratory distress syndrome treated by extracorporeal membrane oxygenation, minimal sedation, and pressure supported ventilation. Intensive Care Med 26(11):1630–1637PubMedPubMedCentralCrossRef
3.
Peek GJ, Mugford M, Tiruvoipati R, CESAR trial collaboration et al (2009) Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet 374(9698):1351–1363PubMedCrossRef
4.
Chen Z, Mondal NK, Zheng S et al (2017) High shear induces platelet dysfunction leading to enhanced thrombotic propensity and diminished hemostatic capacity. Platelets 2017:1–8
5.
Chen Z, Mondal NK, Ding J et al (2016) Paradoxical effect of nonphysiological shear stress on platelets and von willebrand factor. Artif Organs 40:659–668PubMedCrossRef
6.
Abrams D, Baldwin MR, Champion M et al (2016) Thrombocytopenia and extracorporeal membrane oxygenation in adults with acute respiratory failure: a cohort study. Intensive Care Med 42(5):844–852PubMedPubMedCentralCrossRef
7.
Laine A, Niemi T, Suojaranta-Ylinen R et al (2016) Decreased maximum clot firmness in rotational thromboelastometry (ROTEM®) is associated with bleeding during extracorporeal mechanical circulatory support. Perfusion 31(8):625–633PubMedCrossRef
8.
Sokolovic M, Pratt AK, Vukicevic V et al (2016) Platelet count trends and prevalence of heparin-induced thrombocytopenia in a cohort of extracorporeal membrane oxygenator patients. Crit Care Med 44(11):e1031–e1037PubMedCrossRef
9.
Yoshimoto Y, Hasebe T, Takahashi K et al (2013) Ultrastructural characterization of surface-induced platelet activation on artificial materials by transmission electron microscopy. Microsc Res Tech 76:342–349PubMedCrossRef
10.
Heilmann C, Geisen U, Beyersdorf F et al (2012) Acquired von Willebrand syndrome in patients with extracorporeal life support (ECLS). Intensive Care Med 38:62–68PubMedCrossRef
11.
Vaquer S, de Haro C, Peruga P et al (2017) Systematic review and meta-analysis of complications and mortality of veno-venous extracorporeal membrane oxygenation for refractory acute respiratory distress syndrome. Ann Intensive Care 7(1):51PubMedPubMedCentralCrossRef
12.
Zangrillo A, Landoni G, Biondi-Zoccai G et al (2013) A meta-analysis of complications and mortality of extracorporeal membrane oxygenation. Crit Care Resusc 15:172–178PubMed
13.
British Committee for Standards in Haematology, Blood Transfusion Task Force (2003) Guidelines for the use of platelet transfusions. Br J Haematol 122(1):10–23CrossRef
14.
15.
16.
Tauber H, Streif W, Fritz J et al (2016) Predicting transfusion requirements during extracorporeal membrane oxygenation. J Cardiothorac Vasc Anesth 30(3):692–701PubMedCrossRef
17.
Higgins JPT, Green S (2011) Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. The Cochrane Collaboration. www.​handbook.​cochrane.​org. Accessed 14 Dec 2019
18.
Byron CW, Dahabreh IJ, Trikalinos TA et al (2012) Closing the gap between methodologists and end-users: R as a computational back-end. J Stat Softw 49:5
19.
Schwarzer G, Carpenter JR, Rücker G (2015) Meta-analysis with R. Springer, BerlinCrossRef
20.
Gordon M, Lumley T (2019) R package ‘forestplot’. Advanced forest plot using ‘grid’ graphics. The Comprehensive R Archive Network, Vienna
21.
Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558PubMedCrossRef
22.
Sterne JAC, Egger M, Moher D. In: Higgins JPT, Green S (2011) Addressing reporting biases Cochrane handbook for systematic reviews of interventions version 5.1.0. The Cochrane Collaboration
23.
Copas J, Shi JQ (2000) Meta-analysis, funnel plots and sensitivity analysis. Biostatistics 1(3):247–262PubMedCrossRef
24.
Loforte A, Montalto A, Ranocchi F et al (2012) Peripheral extracorporeal membrane oxygenation system as salvage treatment of patients with refractory cardiogenic shock: preliminary outcome evaluation. Artif Organs 36(3):E53–61PubMedCrossRef
25.
Cottini SR, Wenger U, Sailer S et al (2013) Extracorporeal membrane oxygenation: beneficial strategy for lung transplant recipients. J Extra Corpor Technol 45(1):16–20PubMedPubMedCentral
26.
Pieri M, Agracheva N, Bonaveglio E et al (2013) Bivalirudin versus heparin as an anticoagulant during extracorporeal membrane oxygenation: a case-control study. J Cardiothorac Vasc Anesth 27(1):30–34PubMedCrossRef
27.
Mutlak H, Reyher C, Meybohm P et al (2015) Multiple electrode aggregometry for the assessment of acquired platelet dysfunctions during extracorporeal circulation. Thorac Cardiovasc Surg 63(1):21–27PubMedCrossRef
28.
Glick D, Dzierba AL, Abrams D et al (2015) Clinically suspected heparin-induced thrombocytopenia during extracorporeal membrane oxygenation. J Crit Care 30(6):1190–1194PubMedCrossRef
29.
Malfertheiner MV, Philipp A, Lubnow M et al (2016) Hemostatic changes during extracorporeal membrane oxygenation: a prospective randomized clinical trial comparing three different extracorporeal membrane oxygenation systems. Crit Care Med 44(4):747–754PubMedCrossRef
30.
Nair P, Hoechter DJ, Buscher H et al (2015) Prospective observational study of hemostatic alterations during adult extracorporeal membrane oxygenation (ECMO) using point-of-care thromboelastometry and platelet aggregometry. J Cardiothorac Vasc Anesth 29(2):288–296PubMedCrossRef
31.
Opfermann P, Bevilacqua M, Felli A et al (2016) Prognostic impact of persistent thrombocytopenia during extracorporeal membrane oxygenation: a retrospective analysis of prospectively collected data from a cohort of patients with left ventricular dysfunction after cardiac surgery. Crit Care Med 44(12):e1208–e1218PubMedCrossRef
32.
Dzierba AL, Roberts R, Muir J et al (2016) Severe thrombocytopenia in adults with severe acute respiratory distress syndrome: impact of extracorporeal membrane oxygenation use. ASAIO J 62(6):710–714PubMedCrossRef
33.
Lukito P, Wong A, Jing J et al (2016) Mechanical circulatory support is associated with loss of platelet receptors glycoprotein Ibα and glycoprotein VI. J Thromb Haemost 14(11):2253–2260PubMedCrossRef
34.
Laverdure F, Louvain-Quintard V, Kortchinsky T et al (2016) PF4-heparin antibodies during ECMO: incidence, course, and outcomes. Intensive Care Med 42(6):1082–1083PubMedCrossRef
35.
Chung JH, Yeo HJ, Kim D et al (2017) Changes in the levels of beta-thromboglobulin and inflammatory mediators during extracorporeal membrane oxygenation support. Int J Artif Organs 40(10):575–580PubMedCrossRef
36.
Ljajikj E, Zittermann A, Morshuis M et al (2017) Bivalirudin anticoagulation for left ventricular assist device implantation on an extracorporeal life support system in patients with heparin-induced thrombocytopenia antibodies. Interact Cardiovasc Thorac Surg 25(6):898–904PubMedCrossRef
37.
Combes A, Hajage D, Capellier G, EOLIA Trial Group, REVA, and ECMONet et al (2018) Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. N Engl J Med 378(21):1965–1975PubMedCrossRef
38.
Kalbhenn J, Schlagenhauf A, Rosenfelder S et al (2018) Acquired von Willebrand syndrome and impaired platelet function during venovenous extracorporeal membrane oxygenation: Rapid onset and fast recovery. J Heart Lung Transplant 37(8):985–991PubMedCrossRef
39.
Kimmoun A, Oulehri W, Sonneville R et al (2018) Prevalence and outcome of heparin-induced thrombocytopenia diagnosed under veno-arterial extracorporeal membrane oxygenation: a retrospective nationwide study. Intensive Care Med 44(9):1460–1469PubMedCrossRef
40.
Ruggeri L, Franco A, Alba AC et al (2018) Coagulation derangements in patients with refractory cardiac arrest treated with extracorporeal cardiopulmonary resuscitation. J Cardiothorac Vasc Anesth 33(7):1877–1882 PubMedCrossRef
41.
Cavayas YA, Del Sorbo L, Fan E (2018) Intracranial hemorrhage in adults on ECMO. Perfusion 33(1_suppl):42–50PubMedCrossRef
42.
Tabata S, Yamaguchi S, Nagamine H et al (2004) Efficacy of fk633, an ultra-short acting glycoprotein iib/iiia antagonist on platelet preservation during and after cardiopulmonary bypass. Eur J Cardiothorac Surg 26:289–293PubMedCrossRef
43.
Sniecinski RM, Chandler WL (2011) Activation of the hemostatic system during cardiopulmonary bypass. Anesth Analg 113:1319–1333PubMedCrossRef
44.
Varon D, Shai E (2015) Platelets and their microparticles as key players in pathophysiological responses. J Thromb Haemost 13(Suppl 1):S40–46PubMedCrossRef
45.
Vonderheide RH, Thadhani R, Kuter DJ (1998) Association of thrombocytopenia with the use of intra-aortic balloon pumps. Am J Med 105:27–32PubMedCrossRef
46.
Ho LTS, Lenihan M, McVey MJ et al (2019) Transfusion avoidance in cardiac surgery study investigators. The association between platelet dysfunction and adverse outcomes in cardiac surgical patients. Anaesthesia 74(9):1130–1137PubMedCrossRef
47.
48.
Weingart C, Lubnow M, Philipp A, Bein T, Camboni D, Müller T (2015) Comparison of coagulation parameters, anticoagulation, and need for transfusion in patients on interventional lung assist or veno-venous extracorporeal membrane oxygenation. Artif Organs 39(9):765–773PubMedCrossRef
49.
Panigada M, Artoni A, Passamonti SM et al (2016) Hemostasis changes during veno-venous extracorporeal membrane oxygenation for respiratory support in adults. Minerva Anestesiol 82(2):170–179PubMed
50.
51.
Klein S, Hesselmann F, Djeljadini S et al (2020) EndOxy: dynamic long-term evaluation of endothelialized gas exchange membranes for a biohybrid lung. Ann Biomed Eng 48:747–756PubMedCrossRef
52.
53.
Porcelli R, Moskowitz BC, Cetta F et al (2003) Heparin-induced thrombocytopenia with associated thrombosis in children after the Fontan operation: report of two cases. Texas Heart Inst J 30(1):58–61
54.
Warkentin TE, Sheppard JA, Horsewood P et al (2000) Impact of the patient population on the risk for heparin induced thrombocytopenia. Blood 96:1703–1708PubMedCrossRef
55.
Martel N, Lee J, Wells PS (2005) Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis. Blood 106:2710–2715PubMedCrossRef
56.
57.
Lorusso R, Raffa GM, Alenizy K et al (2019) Structured review of post-cardiotomy extracorporeal membrane oxygenation: part 1-Adult patients. J Heart Lung Transplant 38(11):1125–1143PubMedCrossRefPubMedCentral
58.
Yeo HJ, Kim DH, Jeon D, Kim YS, Cho WH (2015) Low-dose heparin during extracorporeal membrane oxygenation treatment in adults. Intensive Care Med 41(11):2020–2021PubMedCrossRef
59.
Selleng S, Selleng K (2016) Heparin-induced thrombocytopenia in cardiac surgery and critically ill patients. Thromb Haemost 116(5):843–851PubMedCrossRef
60.
Mazzeffi M, Tanaka K (2016) Platelets and ECMO: should we worry about count, function, or both? Intensive Care Med 42(7):1199–1200PubMedCrossRef
61.
Mazzeffi M, Gupta R, Lonergan T, Pasrija C, Kon Z, Tanaka K (2017) ABO type and bleeding during adult ECMO. Intensive Care Med 43(2):275–276PubMedCrossRef
62.
Mazzeffi M, Greenwood J, Tanaka K et al (2016) Bleeding, transfusion, and mortality on extracorporeal life support: ECLS working group on thrombosis and hemostasis. Ann Thorac Surg 101(2):682–689PubMedCrossRef
Metadata
Title
Platelets and extra-corporeal membrane oxygenation in adult patients: a systematic review and meta-analysis
Authors
Federica Jiritano
Giuseppe Filiberto Serraino
Hugo ten Cate
Dario Fina
Matteo Matteucci
Pasquale Mastroroberto
Roberto Lorusso
Publication date
01-06-2020
Publisher
Springer Berlin Heidelberg
Published in
Intensive Care Medicine / Issue 6/2020
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-020-06031-4

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