Vadim Kostousov1, Kim Nguyen, Shilpa G Hundalani, Jun Teruya. 1. 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.
Abstract
CONTEXT: 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). OBJECTIVES: 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. DESIGN: 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.
CONTEXT: 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). OBJECTIVES: 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. DESIGN: 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.