PB1138 - Obesity, fibrinolysis, and bleeding in patients with non-severe hemophilia

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Oliver Königsbrügge, MD PhD

Physician Scientist
Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
Vienna, Wien, Austria

Co-Author(s)

JR

Judit Rejtő

Researcher
Medical University of Vienna, Vienna, Austria
Vienna, Wien, Austria
Daniel Kraemmer, MD

PhD Student
Department of Medicine I, Clinical Division of Haematology and Haemostaseology; Medical University of Vienna, Vienna, Austria
Vienna, Wien, Austria
GS

Gerhard Schuster

Attending
Upper Austrian Red Cross
Linz, Oberosterreich, Austria
CF

Clemens Feistritzer

Professor
Internal Medicine V - Hematology and Oncology, Medical University of Innsbruck
Vienna, Wien, Austria
Johanna Gebhart, MD, PhD

Ap. Prof. Dr. PhD
Clinical Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
Vienna, Wien, Austria
Cihan Ay, MD

Professor, Head of the Thrombosis and Haemostasis Research Group
Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
Vienna, Wien, Austria
Ingrid Pabinger, MD

Co-Head of the Thrombosis and Haemostasis Research Group
Clinical Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
Vienna, Wien, Austria

Background: Obesity leads to increased strain on muscles and joints and could be a contributing factor to the burden of disease in patients with non-severe hemophilia. Fatty tissue, however, also plays an active part in the production of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) and therefore balance of fibrinolysis.

Aims: We aimed to investigate the effects of obesity on the frequency of bleeding and fibrinolysis in hemophilia.

Methods: Persons with non-severe hemophilia A or B (PwH) were recruited into a cross-sectional cohort study after informed consent. Frequency of bleeding in the past 5 years was retrospectively recorded. Body-mass index (BMI), FVIII or IX activity, t-PA antigen and activity, and PAI-1 activity were measured.

Results: The cohort includes 90 PwH (74 hemophilia A, 16 hemophilia B) with median age 49.6 years (25th to 75th percentile 34.5–59.9), and median FVIII/FIX level 12% (8–19%). The median BMI was 25.7 kg/m^2 (23.3–28.3), and 14 patients (15.5%) had BMI>30. The median number of bleeding episodes in the past 5 years was 0 (0-1).
In age-adjusted negative binomial regression, factor VIII/IX level (incidence rate ratio [IRR] 0.93 per 1% increase, 95% confidence interval [CI] 0.88-0.98, p< 0.001), and BMI (IRR 0.82 per 1kg/m^2 increase, 95%CI 0.74-0.91, p< 0.001) were independently associated with frequency of bleeding episodes. Factor VIII/IX levels (IRR 0.88, 95%CI 0.80-0.96, p=0.005) and BMI (IRR 0.68, 95%CI 0.55-0.82) were also independently associated with the frequency of joint and muscle bleeding.
BMI correlated with PAI and t-PA antigen levels (rho 0.241, p= 0.025 and 0.257, p= 0.017) and correlated inversely with t-PA activity (rho -0.240, p=0.026).

Conclusion(s): Increasing BMI decreased the number of bleeding episodes and joint and muscle specific bleeding episodes in persons with non-severe hemophilia. The bleeding severity was potentially mitigated by increasing PAI levels and decreasing t-PA activity.