title: Effect of fondaparinux on coagulation assays: results of College of American Pathologists proficiency testing.
abstract: BACKGROUND
  Fondaparinux, a factor Xa inhibitor, is approved for thromboprophylaxis after orthopedic surgery and for treatment of venous thromboembolism. It may also be efficacious, safe, and cost-effective for other patients; thus, more widespread use of fondaparinux is likely. The effect of fondaparinux on coagulation testing needs to be thoroughly examined.
  
  
  OBJECTIVE
  To report the effects of fondaparinux on coagulation tests (prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin, factor VIII, thrombin time, anti-factor Xa) across diverse methodologies.
  
  
  METHODS
  Samples with different concentrations of fondaparinux (0, 0.4, 0.8, and 2.0 microg/mL) were sent to laboratories participating in the College of American Pathologists Comprehensive Coagulation proficiency survey (N = 898). Laboratory-specific methods were used to assay coagulation parameters.
  
  
  RESULTS
  Prophylactic or therapeutic fondaparinux prolonged the prothrombin time by approximately 1 second and the activated partial thromboplastin time by 4 to 5 seconds, and reduced factor VIII from 119% to 107% and 102%, respectively. Supratherapeutic fondaparinux reduced factor VIII to 85%. The activated partial thromboplastin time was prolonged in 19%, 29%, and 52% of laboratories with prophylactic, therapeutic, and supratherapeutic fondaparinux levels, respectively. Fibrinogen, antithrombin, and thrombin time assays did not show clinically significant changes. When measuring fondaparinux concentration using an anti-factor Xa assay, the most accurate results were obtained when fondaparinux was used as the calibrator.
  
  
  CONCLUSIONS
  Fondaparinux, even in prophylactic doses, slightly prolongs the prothrombin time and activated partial thromboplastin time and can interfere with factor VIII assays, but it has no clinically relevant effect on fibrinogen, antithrombin, or thrombin time. A fondaparinux standard curve should be used for reporting fondaparinux levels using an anti-factor Xa assay.
authors.affiliation: Department of Pathology and Laboratory Medicine, Harvard Medical School, Massachusetts General Hospital, Boston 02114, USA.
authors.forename: Agata
authors.initials: A
authors.lastname: Smogorzewska
authors.forename: John T
authors.initials: JT
authors.lastname: Brandt
authors.forename: Wayne L
authors.initials: WL
authors.lastname: Chandler
authors.forename: Mark T
authors.initials: MT
authors.lastname: Cunningham
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Hayes
authors.forename: John D
authors.initials: JD
authors.lastname: Olson
authors.forename: Kandice
authors.initials: K
authors.lastname: Kottke-Marchant
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Van Cott
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D000990:Antithrombin III; D001780:Blood Coagulation Tests; D002138:Calibration; D004305:Dose-Response Relationship, Drug; D005169:Factor VIII / Q000037:antagonists & inhibitors; D000077425:Fondaparinux; D006801:Humans; D009994:Osmolar Concentration; D010314:Partial Thromboplastin Time; D011134:Polysaccharides / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D011517:Prothrombin Time
chemical_list: D000925:Anticoagulants; D011134:Polysaccharides; D000990:Antithrombin III; D005169:Factor VIII; D000077425:Fondaparinux