Activation of the clotting system during extracorporeal membrane oxygenation in term newborn infants.
OBJECTIVE
To determine the degree of clotting activation that occurs with the usual anticoagulation regimen with systemic heparinization.


METHODS
To allow a standardized comparison of the patients, this study focused on the first 48 hours of extracorporeal membrane oxygenation (ECMO) in term newborn infants. The ECMO perfusion circuit consisted of a roller pump, silicone membrane lungs, and silicone rubber tubing. Coagulation was controlled routinely by measuring prothrombin time, fibrinogen, antithrombin III, and reptilase time. Platelet counts, activated clotting time, and heparin concentration were controlled regularly. The following specific activation markers of the clotting system were measured: prothrombin activation fragment 1 + 2(F1+2), thrombin-antithrombin III complexes, and D-dimer. Measurements were done before the start of ECMO, after 5 minutes, and at hours 1, 2, 3, 4, 6, 12, 24 and 48.


RESULTS
All seven term infants had excessively high levels of clotting activation markers within the first 2 hours of ECMO: F1+2, 11.6(+/- O.9) nmol/L (mean +/- SEM); thrombin-antithrombin, 920(+/- 2.2) microg/L; D-dimer, 15.522(+/- 3.689) ng/L. During the next 46 hours of ECMO, F1+2 and thrombin-antithrombin III complexes decreased from those high values, whereas D-dimer did not. The increase of activation markers was accompanied by low fibrinogen, low platelet counts. and prolongation of reptilase time.


CONCLUSIONS
These findings fit the pattern of consumptive coagulopathy during neonatal ECMO, especially in the first 24 hours.
Urlesberger
B
B
Department of Neonatology, ECMO-Center, University of Graz, Austria.
Zobel
G
G
Zenz
W
W
Kuttnig-Haim
M
M
Maurer
U
U
Reiterer
F
F
Riccabona
M
M
Dacar
D
D
Gallisti
S
S
Leschnik
B
B
Muntean
W
W
D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use; D000990:Antithrombin III / Q000032:analysis; D012103:Batroxobin / Q000097:blood; D001777:Blood Coagulation; D004867:Equipment Design; D015199:Extracorporeal Membrane Oxygenation / Q000295:instrumentation; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis; D005500:Follow-Up Studies; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn / Q000097:blood*; D007440:Intubation / Q000295:instrumentation; D008567:Membranes, Artificial; D010446:Peptide Fragments / Q000032:analysis; D010447:Peptide Hydrolases / Q000032:analysis; D010976:Platelet Count; D011516:Prothrombin / Q000032:analysis; D011517:Prothrombin Time; D012826:Silicone Elastomers; D012828:Silicones; D014914:Whole Blood Coagulation Time
D000925:Anticoagulants; D005338:Fibrin Fibrinogen Degradation Products; D008567:Membranes, Artificial; D010446:Peptide Fragments; D012826:Silicone Elastomers; D012828:Silicones; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; C045879:prothrombin fragment 1.2; D000990:Antithrombin III; D011516:Prothrombin; D005340:Fibrinogen; D006493:Heparin; D010447:Peptide Hydrolases; D012103:Batroxobin