Skip to main content
ISTH 2024 Main banner
Back
CME Evaluation

Oral Communication Session

Inherited Bleeding Disorders and Inhibitors

Session: Joint health pathophysiological mechanisms

OC 36.1 - FIX is localised in the vessel wall and can generate thrombin when in complex with collagen IV in human synovial tissues

Monday, June 24, 2024
09:30 – 09:45 ICT
Room: 111 A-C

    Presenting Author(s)

  • Gael Morrow, PhD

    Chancellor's Fellow
    Robert Gordon University
    Aberdeen, Scotland, United Kingdom

    • Co-Author(s)

  • Mike Laffan

    Professor of haemostasis & thrombosis
    Imperial College London, London. UK
    London, England, United Kingdom

  • Nicola Curry, MD, FRCP, FRCPath

    Associate Professor of Haematology
    University of Oxford
    Oxford, England, United Kingdom

Background: Haemophilia B is a blood clotting disorder caused by deficiency in coagulation Factor IX (FIX). Patients are treated by infusion of FIX concentrates based on their plasma concentration. However, FIX also binds reversibly to collagen IV in the basal lamina of blood vessels and may establish and important extravascular store.

Aims: To determine if the FIX-collagen IV complex participates in extravascular coagulation.

Methods: Flat-bottomed plates were coated with collagen IV prior to application of FIX. Thrombin generation (TG) was performed in FIX deficient plasma (FIX-DP) or pooled normal plasma (PNP), initiated with 1 pM tissue factor (TF) and measured using the Calibrated Automated Thrombogram. Different preparations of FIX were compared; Alprolix, Idelvion, Benefix and Replenine. FIX distribution in vivo was studied in sections of synovial tissue from controls and Haemophilia B patients using immunofluorescence.

Results: On surfaces with the FIX-collagen complex present, FIX-DP generated a peak thrombin concentration comparable to PNP. FIX binding was confirmed by a chromogenic activity assay and a dose-dependent effect of FIX coating concentration was observed. Collagen plates coated with extended half-life concentrates, Alprolix and Idelvion, generated a significant increase in the endogenous thrombin potential (ETP), when compared to short-acting concentrate, Replenine and Benefix (* p < 0.01). Conversely, no changes in FIX activity were observed. FIX was located in the vessel, within the vessel wall and in the extravascular space in synovial tissue sections from a Haemophilia B patient. FIX co-localised with collagen IV in the vessel wall and Factor VIII within the blood vessel and in the extravascular space.

Conclusion(s): Our data confirm that FIX binds to collagen IV in human synovial tissue and raises the possibility that the intrinsic tenase may assemble on the collagen surface in the extravascular space.