title: Thrombin generation and factor X assays for the assessment of warfarin anticoagulation in thrombotic antiphospholipid syndrome.
abstract: Monitoring warfarin anticoagulation in patients with thrombotic antiphospholipid syndrome (APS) may be complicated by the sensitivity of different thromboplastins to lupus anticoagulant. The aim of this study was to compare the degree of anticoagulation intensity in thrombotic APS and non-APS patients (50 in each group) on long-term warfarin, by measurement of the INR with two widely available thromboplastins with instrument-specific ISI values, and to investigate the potential role of amidolytic FX levels and thrombin generation (TG) testing in the assessment of anticoagulant intensity in thrombotic APS patients. There were no overall differences in INR between reagents or patient groups, but 20% (10/50) of APS patients showed ≥0.5 INR unit difference between reagents, which would have resulted in altered clinical management in some patients. FX levels were useful in assessing anticoagulation intensity for INR 2.0-3.0, but showed poor utility at INR ≥3.5 where the lowest measured FX level was 12IU/dL. In contrast, ETP and peak thrombin showed significant inverse correlations with the INR, suggesting that TG testing may be helpful in the determination of true anticoagulant intensity in APS patients, including those with ≥3.5 INR. TG testing also highlighted a subgroup of APS patients with increased peak thrombin relative to the intensity of anticoagulation as assessed by INR and FX, suggesting that TG testing may be useful in identifying an ongoing prothrombotic state in patients with apparently adequate anticoagulation intensity as assessed by INR.
authors.affiliation: Haemostasis Research Unit, Department of Haematology, University College London, London, UK. Electronic address: m.efthymiou@ucl.ac.uk.
authors.forename: Maria
authors.initials: M
authors.lastname: Efthymiou
authors.affiliation: Haemostasis Research Unit, Department of Haematology, University College London, London, UK.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Lawrie
authors.affiliation: Haemostasis Research Unit, Department of Haematology, University College London, London, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Mackie
authors.affiliation: Haemostasis Research Unit, Department of Haematology, University College London, London, UK.
authors.forename: Deepa
authors.initials: D
authors.lastname: Arachchillage
authors.affiliation: Haemostasis Research Unit, Department of Haematology, University College London, London, UK.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Lane
authors.affiliation: Haemostasis Research Unit, Department of Haematology, University College London, London, UK.
authors.forename: Samuel
authors.initials: S
authors.lastname: Machin
authors.affiliation: Haemostasis Research Unit, Department of Haematology, University College London, London, UK; Department of Haematology, University College London Hospitals NHS Foundation Trust, London, UK.
authors.forename: Hannah
authors.initials: H
authors.lastname: Cohen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000737:chemistry; D016736:Antiphospholipid Syndrome / Q000097:blood*; D001158:Arteries / Q000473:pathology; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests / Q000379:methods*; D003430:Cross-Sectional Studies; D005170:Factor X / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D016682:Lupus Coagulation Inhibitor / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D011517:Prothrombin Time; D013917:Thrombin / Q000008:administration & dosage* / Q000737:chemistry; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy; D054556:Venous Thromboembolism / Q000097:blood / Q000188:drug therapy; D014859:Warfarin / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D016682:Lupus Coagulation Inhibitor; D014859:Warfarin; D005170:Factor X; D013917:Thrombin
keywords: INR; Thrombotic antiphospholipid syndrome; amidolytic Factor X; thrombin generation