Related Experiment Videos
The mechanisms of platelet dysfunction during extracorporeal membrane oxygenation in critically ill neonates
P Y Cheung1, G Sawicki, E Salas
1Department of Pharmacology, University of Alberta, Edmonton, Canada.
Objective:
Although bleeding associated with thrombocytopenia often complicates extracorporeal membrane oxygenation (ECMO), the mechanisms of platelet dysfunction during ECMO remain poorly understood. We investigated the role of matrix metalloproteinase (MMP)-2, which recently has been shown to mediate a novel pathway of platelet aggregation, in the platelet dysfunction induced by ECMO.
Design:
Prospective longitudinal case study.
Setting:
Level III neonatal intensive care unit.
Patients:
Ten neonates treated with ECMO.
Intervention:
ECMO procedure.
Measurements:
Platelet counts and collagen-induced platelet aggregation ex vivo; plasma markers of platelet (soluble P-selectin) and endothelial (soluble E-selectin and total nitrite/nitrate) activation; plasma MMP-2 and MMP-9 activities; and concentrations of tissue inhibitors of MMPs.
Main Results:
During ECMO, time-dependent platelet activation, as evidenced by thrombocytopenia, decreased platelet aggregation, and increased plasma soluble P-selectin concentrations were found in the absence of endothelial activation, as shown by normal plasma concentrations of soluble E-selectin and nitric oxide metabolites (nitrite/nitrate). There was a time-dependent increase in plasma MMP-2 but not MMP-9 activity; tissue inhibitors of MMPs were not detected. Plasma soluble P-selectin concentrations significantly correlated with simultaneous plasma MMP-2 (r2 = .37, p < .0001) but not with MMP-9 activities. Platelet dysfunction persisted despite repeated platelet transfusions to maintain platelet counts >100 x 10(9)/L.
Conclusions:
ECMO resulted in the activation of platelets but not endothelial cells. During ECMO, platelet dysfunction persisted despite platelet transfusions. MMP-2 may play a role in the development of platelet dysfunction caused by ECMO.
Insights
Extracorporeal membrane oxygenation (ECMO) activates platelets, causing dysfunction that persists despite transfusions. Matrix metalloproteinase (MMP)-2 may contribute to this platelet dysfunction during ECMO.
Area of Science:
- Biomedical Engineering
- Hematology
- Neonatology
Background:
- Bleeding complications, often linked to thrombocytopenia, frequently complicate extracorporeal membrane oxygenation (ECMO) therapy.
- The precise mechanisms underlying platelet dysfunction during ECMO remain incompletely understood, necessitating further investigation.
Purpose of the Study:
- To investigate the potential role of matrix metalloproteinase (MMP)-2 in mediating platelet dysfunction observed during ECMO.
- To explore the relationship between MMP-2 activity and markers of platelet activation in neonates undergoing ECMO.
Main Methods:
- A prospective longitudinal case study was conducted in a Level III neonatal intensive care unit.
- Ten neonates receiving ECMO were monitored, with measurements including platelet counts, collagen-induced platelet aggregation, plasma markers of platelet and endothelial activation, and plasma MMP-2 and MMP-9 activities.
Main Results:
- ECMO led to time-dependent platelet activation, characterized by thrombocytopenia, reduced platelet aggregation, and increased soluble P-selectin, without evidence of endothelial activation.
- Plasma MMP-2 activity increased over time during ECMO, correlating significantly with soluble P-selectin levels, while MMP-9 activity remained unchanged.
- Platelet dysfunction persisted despite therapeutic platelet transfusions, indicating a complex mechanism beyond simple platelet count reduction.
Conclusions:
- ECMO induces platelet activation and dysfunction, independent of endothelial cell activation.
- Matrix metalloproteinase (MMP)-2 emerges as a potential key mediator in the development of ECMO-associated platelet dysfunction.
- The findings suggest that targeting MMP-2 activity could be a future therapeutic strategy to mitigate bleeding complications in patients on ECMO.