title: The influence of free hemoglobin and bilirubin on heparin monitoring by activated partial thromboplastin time and anti-Xa assay.
abstract: BACKGROUND
  Elevated free hemoglobin (Hb) and bilirubinemia complicate extracorporeal membrane oxygenation and could affect unfractionated heparin (UH) therapy monitoring by anti-Xa assay and activated partial thromboplastin time (aPTT).
  
  
  OBJECTIVE
  To compare in vitro response of anti-Xa and aPTT assays to UH in samples with artificial hyperbilirubinemia and hyperhemoglobinemia and to estimate if this interference is also observed in vivo in pediatric extracorporeal membrane oxygenation.
  
  
  METHODS
  Measurement of aPTT and anti-Xa activity in plasma spiked with UH and increased concentration of free Hb and/or conjugated bilirubin. All samples with anti-Xa activity, antithrombin, free Hb, and bilirubin determination and infused dose of UH from inpatients on extracorporeal membrane oxygenation were extracted from the clinical patient database and analyzed.
  
  
  RESULTS
  Each increment of free Hb by 100 mg/dL significantly shortened aPTT, whereas an increment of bilirubin by 6 mg/dL caused significant prolongation of aPTT and stepwise increase of free Hb and/or bilirubin in plasma decreased anti-Xa activity by 0.03 to 0.05 IU/mL. Extracorporeal membrane oxygenation samples with free Hb 50 mg/dL or greater had significantly lower anti-Xa activity compared with normal ones: 0.33 (0.25-0.42) versus 0.4 (0.31-0.48) IU/mL (P = .01), despite the identical UH infusion and similar antithrombin activity. Moderate increase of free Hb by 59 mg/dL was associated with absolute decrease of anti-Xa activity by 0.07 IU/mL.
  
  
  CONCLUSIONS
  Activated partial thromboplastin time and anti-Xa assay are affected by elevated level of free Hb and/or bilirubin in the presence of UH, and lower anti-Xa activity is noted in extracorporeal membrane oxygenation patients with elevated free Hb. Severe hemolysis and/or hyperbilirubinemia could compromise UH monitoring based on these assays.
authors.affiliation: From the Department of Pathology & Immunology (Drs Kostousov and Teruya), Pediatrics (Drs Hundalani and Teruya), and Medicine (Dr Teruya), Baylor College of Medicine, and the Division of Transfusion Medicine & Coagulation (Drs Kostousov and Teruya and Ms Nguyen) and the Department of Pediatrics, Section of Neonatology (Dr Hundalani), Texas Children's Hospital, Houston.
authors.forename: Vadim
authors.initials: V
authors.lastname: Kostousov
authors.forename: Kim
authors.initials: K
authors.lastname: Nguyen
authors.forename: Shilpa G
authors.initials: SG
authors.lastname: Hundalani
authors.forename: Jun
authors.initials: J
authors.lastname: Teruya
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage / Q000097:blood; D001663:Bilirubin / Q000097:blood*; D002675:Child, Preschool; D015199:Extracorporeal Membrane Oxygenation; D065427:Factor Xa Inhibitors / Q000097:blood*; D005260:Female; D006454:Hemoglobins / Q000032:analysis*; D006493:Heparin / Q000008:administration & dosage / Q000097:blood*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010314:Partial Thromboplastin Time; D011446:Prospective Studies
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D006454:Hemoglobins; D006493:Heparin; D001663:Bilirubin