title: Local verification and assignment of mean normal prothrombin time and International Sensitivity Index values across various instruments: recent experience and outcome from North America.
abstract: Warfarin dosing relies on accurate measurements of international normalized ratio (INR), which is calculated from the prothrombin time (PT), International Sensitivity Index international sensitivity index (ISI) of the thromboplastin, and the geometric mean of normal PT (MNPT). However, ISI assignments of certain reagent/instrument combinations are frequently unavailable, especially when the reagent and instrument are not from the same manufacturer. The effort to be in compliance with widely endorsed Clinical and Laboratory Standards Institute (CLSI) guidelines by locally verifying or assigning an ISI to an unsupported reagent/instrument combination is further hindered by the lack of US Food and Drug Administration (FDA)-approved certified plasmas designated for a particular reagent/instrument combination. The objectives of the study include development of a process to verify/assign ISI and MNPT of a single thromboplastin reagent from one manufacturer across multiple instruments including several from another manufacturer and across several campuses of a single institution, the Mayo Clinic. In this study, RecombiPlasTin 2G (R2G), was evaluated on the ACL TOP 700 (IL), STA-R Evolution, STA Compact, and STA Satellite. Random normal donor samples (n = 25) were used to verify/assign MNPT. A subset of the normal donors (n = 8) and 13 warfarin pools (INR range: 1.3-3.9), created from stable warfarin patient plasma, were used for ISI verification/assignment. The manufacturer's assigned ISI was first verified on the ACL TOP 700 (reference method), then assigned on three unsupported instruments using orthogonal regression analysis. The MNPT and manufacturer assigned ISI (11.0, 0.95) were verified on the ACL TOP 700 and subsequently assigned on the STA-R Evolution (11.6, 1.04); STA Compact (11.5, 1.02); and STA Satellite (10.9, 0.99). Linear correlations of the INR results from all the four instruments demonstrated an r2 > 0.99. This process provides a reproducible approach to assigning ISIs on unsupported reagent/instrument combinations. Our data also confirm that ISIs of the same PT reagent differ significantly on different instruments, thus confirming the requirement for evaluations and validation of ISIs for different reagent/instrument combinations.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, Minnesota.
authors.forename: Julie I
authors.initials: JI
authors.lastname: Tange
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, Minnesota.
authors.forename: Diane
authors.initials: D
authors.lastname: Grill
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, Minnesota.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Koch
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, Minnesota.
authors.forename: Roxanne J
authors.initials: RJ
authors.lastname: Ybabez
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, Minnesota.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Krekelberg
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, Minnesota.
authors.forename: Kara A
authors.initials: KA
authors.lastname: Fylling
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, Minnesota.
authors.forename: Cynthia R
authors.initials: CR
authors.lastname: Wiese
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, Minnesota.
authors.forename: Nikola A
authors.initials: NA
authors.lastname: Baumann
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, Minnesota.
authors.forename: Darci R
authors.initials: DR
authors.lastname: Block
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, Minnesota.
authors.forename: Brad S
authors.initials: BS
authors.lastname: Karon
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, Minnesota.
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, Minnesota.
authors.forename: Rajiv K
authors.initials: RK
authors.lastname: Pruthi
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics; D001782:Blood Donors; D005260:Female; D006801:Humans; D019934:International Normalized Ratio / Q000295:instrumentation / Q000379:methods / Q000592:standards; D008297:Male; D011517:Prothrombin Time / Q000295:instrumentation / Q000379:methods / Q000592:standards; D014481:United States; D014859:Warfarin / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D000925:Anticoagulants; D014859:Warfarin