Fibrinolysis as a Causative Mechanism for Bleeding Complications on Extracorporeal Membrane Oxygenation: A Pilot Observational Prospective Study

Author:

Helms Julie1ORCID,Curtiaud Anaïs2,Severac François3,Tschirhart Marine4,Merdji Hamid5,Bourdin Matthieu6,Contant Geneviève7,Depasse François8,Abou Rjeily Ramy9,Sattler Laurent10,Meziani Ferhat11,Angles-Cano Eduardo12

Affiliation:

1. 1Strasbourg University (UNISTRA); Strasbourg University Hospital, Medical Intensive Care Unit (NHC), Strasbourg, France; INSERM (French National Institute of Health and Medical Research), Unit 1260, Regenerative Nanomedicine, Medicine Federation of Strasbourg, Strasbourg, France.

2. 2Strasbourg University (UNISTRA); Strasbourg University Hospital, Medical Intensive Care Unit (NHC), Strasbourg, France; INSERM (French National Institute of Health and Medical Research), Unit 1260, Regenerative Nanomedicine, Medicine Federation of Strasbourg, Strasbourg, France.

3. 3Strasbourg University Hospital, Clinical Research Methods Group (GMRC), Strasbourg, France.

4. 4INSERM (French National Institute of Health and Medical Research), Unit 1260, Regenerative Nanomedicine, Medicine Federation of Strasbourg, Strasbourg, France.

5. 5Strasbourg University (UNISTRA); Strasbourg University Hospital, Medical Intensive Care Unit (NHC), Strasbourg, France; INSERM (French National Institute of Health and Medical Research), Unit 1260, Regenerative Nanomedicine, Medicine Federation of Strasbourg, Strasbourg, France.

6. 6Diagnostica Stago, Prospective Research Department, Gennevilliers, France.

7. 7Diagnostica Stago, Prospective Research Department, Gennevilliers, France.

8. 8Diagnostica Stago, Clinical Development, Asnières sur Seine, France.

9. 9Paris Cite University–INSERM U-1140, Innovative Therapies in Haemostasis, Paris, France.

10. 10Strasbourg University Hospital, Laboratory of Hematology, Hautepierre, Strasbourg, France.

11. 11Strasbourg University (UNISTRA); Strasbourg University Hospital, Medical Intensive Care Unit (NHC), Strasbourg, France; INSERM (French National Institute of Health and Medical Research), Unit 1260, Regenerative Nanomedicine, Medicine Federation of Strasbourg, Strasbourg, France.

12. 12Paris Cite University–INSERM U-1140, Innovative Therapies in Haemostasis, Paris, France.

Abstract

Background Extracorporeal membrane oxygenation (ECMO) is associated with a high risk of bleeding complications. The specific impact of ECMO on fibrinolysis remains unexplored. The objective of the current pilot observational prospective study was to investigate the longitudinal dynamics of fibrinolytic markers—i.e., changes over time—in the context of bleeding events in patients on ECMO. Methods Longitudinal dynamics of contact phase components (kininogen and bradykinin) and fibrinolysis markers (tissue plasminogen activator [tPA], plasminogen activator inhibitor-1 [PAI-1], their complexes [tPA•PAI-1], plasmin–antiplasmin complexes, plasminogen, and D-dimer) were measured in patients undergoing venovenous and venoarterial ECMO, before implantation, at 0, 6, and 12 h after implantation, and daily thereafter. Results The cohort consisted of 30 patients (214 ECMO days). The concentrations of tPA, D-dimer, plasmin–antiplasmin complexes, PAI-1, and tPA•PAI-1 complexes were increased, whereas plasminogen decreased compared to normal values. A noteworthy divergence was observed between hemorrhagic and nonhemorrhagic patients: in bleeding patients, D-dimer, plasmin–antiplasmin, tPA, PAI-1, and tPA•PAI-1 followed an increasing kinetics before hemorrhage and then decreased to their baseline level; conversely, nonbleeding patients showed a decreasing kinetics in these markers. Also, D-dimer and tPA followed an increasing kinetics in bleeding patients compared to nonbleeding patients (median values for D-dimer dynamics: 1,080 vs. –440 ng/ml, P = 0.05; tPA dynamics: 0.130 vs. 0.100 nM, P = 0.038), and both markers significantly increased the day before hemorrhage. A tPA concentration above 0.304 nM was associated with bleeding events (odds ratio, 4.92; 95% CI, 1.01 to 24.08; P = 0.049). Conclusions Contact activation induces fibrinolysis in ECMO patients, especially in patients experiencing bleeding. This finding supports the role of this mechanism as a possible causal factor for hemorrhages during ECMO and open new avenues for novel therapeutic perspectives. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Publisher

Ovid Technologies (Wolters Kluwer Health)

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