Skip to main content
ISTH 2024 Main banner
Back
CME Evaluation

Oral Communication Session

Inherited Bleeding Disorders and Inhibitors

Session: Laboratory testing in bleeding disorders

OC 27.2 - Comparing thrombin generation in hemophilia A and patients with non-valvular atrial fibrillation on vitamin K antagonists

Sunday, June 23, 2024
15:00 – 15:15 ICT
Room: 210 A-D

    Presenting Author(s)

  • Daniel Kraemmer, MD

    PhD Student
    Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna
    Vienna, Wien, Austria

    • Co-Author(s)

  • Cihan Ay, MD

    Professor
    Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna
    Vienna, Wien, Austria

  • JR

    Judit Rejtő

    MD PhD
    Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna
    Vienna, Wien, Austria

  • PQ

    Peter Quehenberger

    Professor
    Department of Laboratory Medicine, Medical University of Vienna
    Vienna, Wien, Austria

  • Ingrid Pabinger

    Professor
    Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna
    Vienna, Wien, Austria

  • Oliver Königsbrügge, MD PhD

    Physician
    Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna
    Vienna, Wien, Austria

Background: Recently published guidelines on antithrombotic treatment in persons with hemophilia (PWH) appraised the literature on whether PWH are naturally anticoagulated: Only two studies compared thrombin generation (TG) in PWH and patients on vitamin K antagonists (VKA), both analyzing endogenous thrombin potential (ETP) and limited by arbitrary stratifications.

Aims: To compare TG in PWHA at varying factor (F) VIII concentrations with patients on VKA.

Methods: We sampled plasma from PWHA of all severities participating in our biobank and from participants on VKA of our hospital-based registry on patients with non-valvular atrial fibrillation (AF). TG was measured by a commercially available assay (Technothrombin, Technoclone) and FVIII levels by chromogenic substrate assay (Biophen, Hyphen Biomed). We regressed 1) ETP on FVIII and 2) INR on ETP in PWHA and VKA samples, respectively. Estimating ETP in 1) and INR at those values in 2) allowed us to compare INR and FVIII by ETP, computing 95% compatibility intervals (95%CI) via bootstrap.

Results: We collected 372 samples from 112 PWHA (mean±SD age, 40±15 years) and 115 AF patients on VKA (72±8 years). Median (IQR) INR and FVIII was 2.0 (1.7-3.4) and 13 IU/dL (3-38), respectively. TG parameters showed substantial heterogeneity, particularly in FVIII samples. TG curves had lower ETP and higher lag time in VKA without a correlate at similar peak thrombin values in FVIII samples (Figure 1). Comparing INR and FVIII by ETP revealed an estimated mean INR-equivalence of 2.1 (95%CI, 1.8-2.2) in PWHA < 1 IU/dL followed by a rapid decline and plateau of 1.4 (95%CI, 1.2-1.5) at 10 IU/dL (Figure 2).

Conclusion(s): TG showed substantial variability and differed distinctly between PWHA and AF patients on VKA irrespective of INR and FVIII. Our data on ETP was incompatible with a guideline-concluded threshold of 10 IU/dL for indicating natural anticoagulation in PWHA similar to therapeutic INR in VKA patients.