The mechanisms of platelet dysfunction during extracorporeal membrane oxygenation in critically ill neonates.
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.


METHODS
Prospective longitudinal case study.


METHODS
Level III neonatal intensive care unit.


METHODS
Ten neonates treated with ECMO.


METHODS
ECMO procedure.


METHODS
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.


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.
Cheung
P Y
PY
Department of Pharmacology, University of Alberta, Edmonton, Canada.
Sawicki
G
G
Salas
E
E
Etches
P C
PC
Schulz
R
R
Radomski
M W
MW
D000704:Analysis of Variance; D001724:Birth Weight; D003422:Critical Care; D015199:Extracorporeal Membrane Oxygenation / Q000009:adverse effects*; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007363:Intensive Care Units, Neonatal; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D009566:Nitrates / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects*; D010976:Platelet Count; D011480:Protease Inhibitors / Q000494:pharmacology*; D012127:Respiratory Distress Syndrome, Newborn / Q000628:therapy*; D019087:Selectins / Q000097:blood; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000494:pharmacology*
D009566:Nitrates; D011480:Protease Inhibitors; D019087:Selectins; D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2