title: Verification of the guidelines for lupus anticoagulant detection: usefulness of index for circulating anticoagulant in APTT mixing test.
abstract: BACKGROUND
  Lupus anticoagulant (LA) is an antibody that interferes with one or more in vitro coagulation reactions, which are dependent on interactions with protein-phospholipid complexes. For LA diagnosis, a mixing test is considered useful for differentiating the inhibitor from a factor deficiency. However, the usefulness and the index of circulating anticoagulant (ICA) in a mixing test with activated partial thromboplastin time (APTT) has not been adequately investigated, and there is scant information regarding the effects of warfarin, heparin, and hemophilia plasma on ICA. We evaluated the usefulness of ICA by investigating the correlation of that index with international normalized ratio (INR), heparin concentration, and factor VIII activity in hemophilia patients.
  
  
  METHODS
  We examined samples from 28 patients positive for LA, 23 receiving warfarin, 19 receiving unfractionated heparin, and 29 with hemophilia A, as well as 61 normal samples. APTT-SLA, Actin FSL, APTT-SP, and PTT-LA were used as reagents in this study.
  
  
  RESULTS
  The correlation coefficient values between ICA and INR, heparin concentration, and factor VIII activity ranged from 0.031-0.342, 0.764-0.843, and 0.564-0.754, respectively, with the 4 reagents. The ICA values for the LA-positive samples were significantly higher than for the normal, warfarin, heparin, and hemophilia samples with all APTT reagents. Samples with a high heparin concentration above approximately 0.5U/ml showed ICA values greater than 15.
  
  
  CONCLUSIONS
  ICA was able to distinguish LA-positive samples from the normal, warfarin, and hemophilia samples, but not heparin samples. ICA calculated from APTT clotting time is useful for LA diagnosis.
authors.affiliation: Department of Molecular Biosciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan; Hemostasis Product Engineering, Sysmex Corporation, Kobe, Hyogo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kumano
authors.affiliation: Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan; Department of Clinical Laboratory, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan. Electronic address: iekom@hoku-iryo-u.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ieko
authors.affiliation: Department of Clinical Laboratory, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan.
authors.forename: Sumiyoshi
authors.initials: S
authors.lastname: Naito
authors.affiliation: Department of Clinical Laboratory, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Hemostasis Product Engineering, Sysmex Corporation, Kobe, Hyogo, Japan; Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Molecular Biosciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Aoki
mesh_terms: D000925:Anticoagulants / Q000032:analysis / Q000627:therapeutic use; D016736:Antiphospholipid Syndrome / Q000097:blood; D005169:Factor VIII / Q000032:analysis; D006467:Hemophilia A / Q000097:blood; D006493:Heparin / Q000032:analysis / Q000627:therapeutic use; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis / Q000097:blood*; D019934:International Normalized Ratio; D016682:Lupus Coagulation Inhibitor / Q000032:analysis / Q000097:blood*; D010314:Partial Thromboplastin Time / Q000379:methods*; D012680:Sensitivity and Specificity; D014859:Warfarin / Q000032:analysis / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D007136:Immunoglobulins; D016682:Lupus Coagulation Inhibitor; C019158:circulating anticoagulants; D014859:Warfarin; D005169:Factor VIII; D006493:Heparin
keywords: Antiphospholipid syndrome; Diagnosis; Lupus coagulation inhibitor; Partial thromboplastin time