title: Age-based difference in activation markers of coagulation and fibrinolysis in extracorporeal membrane oxygenation.
abstract: OBJECTIVE
  Coagulation system activation in extracorporeal membrane oxygenation results in hemostatic derangements. Thrombin generation markers like prothrombin fragment 1+2 and thrombin-antithrombin complex are sensitive markers of hypercoagulability. Plasmin-antiplasmin complex is a sensitive marker for fibrinolysis. D-dimers reflect thrombin generation and fibrinolysis. The aim was to identify the extent of hemostasis activation during extracorporeal membrane oxygenation by measuring thrombin-antithrombin complex, prothrombin fragment 1+2, plasmin-antiplasmin complex, and D-dimer.
  
  
  METHODS
  Prospective cohort study.
  
  
  METHODS
  Tertiary care academic center.
  
  
  METHODS
  Children placed on extracorporeal membrane oxygenation from April 2011 to January 2013.
  
  
  METHODS
  Prothrombin fragment 1+2, thrombin-antithrombin complex, plasmin-antiplasmin complex, and D-dimer were measured on days 1 and 5 of extracorporeal membrane oxygenation.
  
  
  RESULTS
  Data presented as median (interquartile range); nonparametric tests were done using SPSS. Twenty-nine children (52% < 30 d old [neonates], median extracorporeal membrane oxygenation length 151 hr) were studied. Complications included thrombosis in 14%, bleeding in 45%, and thrombosis and bleeding together in 10%. Thrombin-antithrombin complex, prothrombin fragment 1+2, plasmin-antiplasmin complex, and D-dimer levels were high on day 1 and remained increased on extracorporeal membrane oxygenation. In neonates, all levels were higher on day 5 compared with day 1: thrombin-antithrombin complex (55.6 μg/L [30.7-76.0] vs 18.7 μg/L [10.9-34.6]; p = 0.03), prothrombin fragment 1+2 (2,038 pmol/L [1,093-4,018.5] vs 377.5 pmol/L [334.3-1,103.0]; p = 0.00), plasmin-antiplasmin complex (2,160 μg/L [786-3,090] vs 398 μg/L [296.8-990.8]; p = 0.00), and D-dimer (3.0 μg/mL [1.9-11.5] vs 1.5 μg/mL [0.6-2.9]; p = 0.01). Thrombin-antithrombin complex, prothrombin fragment 1+2, plasmin-antiplasmin complex, and D-dimer levels did not correlate with anti-Xa activity or heparin dose. In bleeders older than 30 days, plasmin-antiplasmin complex stayed elevated on day 5, but in patients with no bleeding complications, plasmin-antiplasmin level showed a declining trend. In neonates, plasmin-antiplasmin levels increased over the course of extracorporeal membrane oxygenation irrespective of bleeding.
  
  
  CONCLUSIONS
  Despite our best efforts at adequate anticoagulation with unfractionated heparin, neonates showed persistent increase in coagulation activation on extracorporeal membrane oxygenation. Fibrinolysis activation may contribute to bleeding in patients older than 30 days. Different anticoagulation protocols should be individualized based on age.
authors.affiliation: 1Section of Neonatology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX. 2Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX. 3Department of Pathology & Immunology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX. 4Cancer and Hematology Centers, Baylor College of Medicine, Texas Children's Hospital, Houston, TX. 5Department of Medicine, Baylor College of Medicine, Texas Children's Hospital, Houston, TX.
authors.forename: Shilpa G
authors.initials: SG
authors.lastname: Hundalani
authors.forename: Kim T
authors.initials: KT
authors.lastname: Nguyen
authors.forename: Esther
authors.initials: E
authors.lastname: Soundar
authors.forename: Vadim
authors.initials: V
authors.lastname: Kostousov
authors.forename: Lisa
authors.initials: L
authors.lastname: Bomgaars
authors.forename: Alicia
authors.initials: A
authors.lastname: Moise
authors.forename: Shiu-Ki R
authors.initials: SK
authors.lastname: Hui
authors.forename: Jun
authors.initials: J
authors.lastname: Teruya
mesh_terms: D000367:Age Factors; D000925:Anticoagulants / Q000008:administration & dosage; D000990:Antithrombin III; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000502:physiology; D015199:Extracorporeal Membrane Oxygenation / Q000009:adverse effects*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D005341:Fibrinolysin / Q000378:metabolism*; D005342:Fibrinolysis / Q000502:physiology; D006470:Hemorrhage / Q000097:blood / Q000209:etiology; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010446:Peptide Fragments / Q000097:blood*; D010447:Peptide Hydrolases / Q000097:blood*; D011446:Prospective Studies; D011516:Prothrombin; D013927:Thrombosis / Q000097:blood / Q000209:etiology; D013997:Time Factors; D000979:alpha-2-Antiplasmin / Q000378:metabolism*
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; D000979:alpha-2-Antiplasmin; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; C037742:plasmin-plasmin inhibitor complex; C045879:prothrombin fragment 1.2; D000990:Antithrombin III; D011516:Prothrombin; D006493:Heparin; D010447:Peptide Hydrolases; D005341:Fibrinolysin