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Assessment and Comparison of Acquired Activated Protein C Resistance with Two Thrombin Generation Methods, CAT and ST-Genesia, in APS and SLE Patients

1University College of London, Haemostasis Research Unit, Department of Haematology, London, United Kingdom, 2University College London, Centre for Rheumatology, Division of Medicine, London, United Kingdom, 3University College London Hospitals NHS Foundation Trust, Department of Rheumatology, London, United Kingdom, 4University College London Hospitals NHS Foundation Trust, Clinical Haematology, London, United Kingdom

Abstract Number: PB1904

Meeting: ISTH 2020 Congress

Theme: Thrombotic Microangiopathies » Antiphospholipid Syndrome

Background: Acquired resistance to the anticoagulant actions of activated protein C (APCr) may contribute to thrombotic risk. Using the thrombin generation (TG) system and the CAT machine, we showed that antiphospholipid syndrome (APS) patients with previous venous thromboembolism and systemic lupus erythematosus (SLE) patients exhibit increased APCr.

Aims: The aim of this study was to evaluate the prevalence of APCr using the ST-Genesia system in the presence/absence of thrombomodulin (TM) in APS and SLE patients and to compare APCr results obtained with the CAT machine using rhAPC and Protac®.

Methods: In this cross-sectional study, patient groups tested comprised: 75 normal controls (NC), 68 thrombotic (single or double aPL positive) APS patients, 38 SLE non-thrombotic (17 aPL+, 20 aPL-), 23 APS pregnancy morbidity (PM), 15 triple aPL+ patients and 36 thrombotic controls were tested. Patients on anticoagulation were tested in 1:1: mixture with pooled normal plasma. Samples were tested with the ST‐Genesia system using STG‐ThromboScreen with/without TM and the CAT system using PPP‐reagent (5‐picomolar TF) (Stago) in the presence of rhAPC or Protac®. APCr defined as %inhibition of ETP below the 99th centile of NC; rhAPC (56%); Protac® (63%), -/+TM (38.9%).

Results: % inhibition of ETP in the presence of TM was significantly lower in APS patients (median, confidence intervals): 48.2% (40.7-55.5%) compared to thrombotic controls
(66.3%, 61.7-72.3%, p < 0.0001), but there were no differences between APS and SLE patients. PM (36.9%, 21.9-49.0%) exhibited higher APCr (lower % inhibition of ETP) compared to thrombotic APS patients (p=0.03). APCr results with the ST-Genesia in the presence of TM were comparable to those obtained with the CAT machine with rhAPC or Protac® for all patient groups.

Conclusions: In APS and SLE patients, TG performed with CAT and with ST-Genesia provided similar results and highlighted potentially important differences in APCr between different clinical phenotypes.

To cite this abstract in AMA style:

Lane PJ, Mackie I, Isenberg D, Cohen H, Efthymiou M. Assessment and Comparison of Acquired Activated Protein C Resistance with Two Thrombin Generation Methods, CAT and ST-Genesia, in APS and SLE Patients [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/assessment-and-comparison-of-acquired-activated-protein-c-resistance-with-two-thrombin-generation-methods-cat-and-st-genesia-in-aps-and-sle-patients/. Accessed September 29, 2023.

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