PB0311 - Association of ADAMTS13 activity with clinical parameters and bleeding phenotype in patients with bleeding disorder of unknown cause

Sunday, June 23, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Dino Mehic

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

Co-Author(s)

Tim Dreier, MD

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

PhD Student/MD
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
Cihan Ay, MD

Professor
Division of Hematology and Hemostaseology, Department of Medicine I, 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
Johanna Gebhart

Assoc. Professor
Department of Internal Medicine I, Clinical Division of Hematology and Haemostaseology, Medical University of Vienna
Vienna, Wien, Austria

Background: Patients with bleeding disorder of unknown cause (BDUC) exhibit a bleeding tendency, but no abnormalities in hemostatic investigations. ADAMTS13 regulates the multimeric size of von Willebrand factor (VWF). An imbalanced VWF-ADAMTS13 axis has been associated with adverse outcomes in liver disease and COVID-19. Blood group O (BGO) is overrepresented in BDUC and is associated with lower von VWF levels as well as enhanced susceptibility of VWF to ADAMTS13 proteolysis.

Aims: To investigate ADAMTS13 activity and its association with bleeding severity, VWF and BGO in BDUC patients.

Methods: Adult patients with BDUC or VWD from the Vienna bleeding biobank (EC603/2009) and healthy controls (HC, n=141, EC039/2006) were included. ADAMTS13 activity was determined by ELISA (Technozym®, Technoclone, Vienna, Austria).

Results: Clinical characteristics are shown in Table 1. After adjustment for age and sex, ADAMTS13 was lower in BDUC patients compared to HC, but not compared to VWD. VWF/ADAMTS13 ratios were higher in BDUC than in HC or VWD (Table 1).
In BDUC, ADAMTS13 correlated weakly with age (Spearman r:-0.22), but not with bleeding severity (not shown) or VWF levels (Figure 1).
In multivariable analysis, BGO (β=-7.64, p=0.034) and VWF:Act (β=-0.18, p=0.012), but not VWF:Ag (β=-0.01, p=0.956), factor VIII activity (β =0.06,p=0.328) or fibrinogen levels (β=-0.03, p=0.272) were associated with lower ADAMTS13 activity.
BDUC patients with BGO (vs. non-O) had lower levels of VWF:Ag [median (IQR) 87 (76, 100) vs. 114 (92, 145), p<.001], VWF:Act [75 (66, 90) vs. 112 (79, 146), p<.001] but not ADAMTS13 [105 (93, 120) vs. 103 (91, 128), p=0.9]. The predicted mean values of ADAMTS13, holding VWF:Ag [mean difference (95% CI): -7.6 (-14.8,-0.5)] and VWF:Act [-8.6 (-15.7,-1.5)] levels constant in regression analysis, were lower in patients with BGO (Figure 1).

Conclusion(s): Reduced ADAMTS13 activity and high VWF/ADAMTS13 ratios may reflect a counterregulatory mechanism in BDUC.