Shear-induced acquired von Willebrand syndrome: an accomplice of bleeding events in adults on extracorporeal membrane oxygenation support

Wang, Haiwang; Li, Duo; Chen, Yuansen; Liu, Ziquan; Liu, Yanqing; Meng, Xiangyan; Fan, Haojun; Hou, Shike

doi:10.3389/fcvm.2023.1159894

Cited by 5 publications

(1 citation statement)

References 81 publications

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“…Another pathophysiologic mechanism that might have contributed to bleeding on ECMO is the development of a multifactorial coagulopathy. 5,21 This coagulopathy may be attributed either to the circuit itself, with factors such as shear-induced abnormal primary hemostasis due to acquired von Willebrand syndrome, 22,23 platelet consumption and/or dysfunction, hemodilution, and consumption of coagulation factors, or to the underlying disease that necessitated ECMO implantation. 24 In our cohort, neither thrombocytopenia nor alterations in prothrombin time were found to be associated with bleeding.…”

Section: Discussionunclassified

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

Helms,

Curtiaud,

Severac

et al. 2024

Anesthesiology

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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-type plasminogen activator [t-PA], plasminogen activator inhibitor-1 [PAI-1], their complexes [t-PA•PAI-1], plasmin-antiplasmin complexes, plasminogen, and D-dimer) were measured in patients undergoing veno-venous and veno-arterial ECMO, before implantation, at 0, 6, and 12 hours post-implantation, and daily thereafter. Results The cohort consisted of 30 patients (214 ECMO-days). The concentrations of t-PA, D-dimer, plasmin-antiplasmin complexes, PAI-1 and t-PA•PAI-1 complexes were increased, whereas plasminogen decreased compared to normal values. A noteworthy divergence was observed between hemorrhagic and non-hemorrhagic patients: in bleeding patients, D-dimer, plasmin-antiplasmin, t-PA, PAI-1 and t-PA•PAI-1 followed an increasing kinetics before hemorrhage and then decreased to their baseline level; conversely non-bleeding patients showed a decreasing kinetics in these markers. Also, D-dimer and t-PA followed an increasing kinetics in bleeding patients compared to non-bleeding patients (median values for D-dimer dynamics: 1080 vs. -440 ng/mL, p=0.05; t-PA dynamics: 0.130 vs. 0.100 nM, p=0.038), and both markers significantly increased the day before hemorrhage. A t-PA concentration above 0.304 nM was associated with bleeding events (OR 4.92, 95% CI [1.01-24.08], p=0.049). Conclusion 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. What we already know about this topic: Extracorporeal membrane oxygenation (ECMO) is associated with a high risk of bleeding complications due to multiple factors. However, the role of the fibrinolytic system is not well understood in this setting. What this article tells us that is new: In patients requiring cardiac and/or pulmonary support with ECMO, D-dimer and tissue plasminogen activator levels were increased with bleeding, findings consistent with fibrinolysis. Although there are multiple causes for fibrinolysis during ECMO, their study suggests that patients who bled had increased contact activation, and may benefit from novel therapeutic agents that inhibit hemostatic activation through this pathway.

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Section: Discussionunclassified

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

Helms,

Curtiaud,

Severac

et al. 2024

Anesthesiology

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Critical hematological parameters in bleeding during extracorporeal membrane oxygenation support

Trieu,

Mai,

Pham

2024

J Artif Organs

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Progress in von Willebrand Disease Treatment: Evolution towards Newer Therapies

Moser,

Schoergenhofer,

Jilma

2024

Semin Thromb Hemost

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Abstractvon Willebrand disease (VWD) is a very heterogenous disease, resulting in different phenotypes and different degrees of bleeding severity. Established therapies (i.e., desmopressin, antifibrinolytic agents, hormone therapy for heavy menstrual bleeding, and von Willebrand factor [VWF] concentrates) may work in some subtypes, but not in all patients. In recent years, progress has been made in improving the diagnosis of VWD subtypes, allowing for more specific therapy. The impact of VWD on women's daily lives has also come to the fore in recent years, with hormone therapy, tranexamic acid, or recombinant VWF as treatment options. New treatment approaches, including the replacement of lacking factor VIII (FVIII) function, may work in those subgroups affected by severe FVIII deficiency. Reducing the clearance of VWF is an alternative treatment pathway; for example, rondaptivon pegol is a VWFA1 domain-binding aptamer which not only improves plasma VWF/FVIII levels, but also corrects platelet counts in thrombocytopenic type 2B VWD patients. These approaches are currently in clinical development, which will be the focus of this review. In addition, half-life extension methods are also important for the improvement of patients' quality of life. Targeting specific mutations may further lead to personalized treatments in the future. Finally, a few randomized controlled trials, although relatively small, have been published in recent years, aiming to achieve a higher level of evidence in future guidelines.

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Shear-induced acquired von Willebrand syndrome: an accomplice of bleeding events in adults on extracorporeal membrane oxygenation support

Cited by 5 publications

References 81 publications

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

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

Critical hematological parameters in bleeding during extracorporeal membrane oxygenation support

Progress in von Willebrand Disease Treatment: Evolution towards Newer Therapies

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