PB0411 - Platelet glycoprotein IIb- and IIIa levels are altered in persistently lupus anticoagulant positive patients with a history of thrombosis

Sunday, June 25, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Theresa Schramm, MSc

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

Co-Author(s)

AS

Anahita Sedighi

Master Student
Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Austria
Vienna, Wien, Austria
FH

Felicia Hsu

Master Student
Institute of Vascular Biology and Thrombosis Research, Centre for Physiology and Pharmacology, 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
Cihan Ay, MD (he/him/his)

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
Johanna Gebhart, MD, PhD (she/her/hers)

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

Maria Zellner

Senior Scientist
Institute of Vascular Biology and Thrombosis Research, Centre for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria
Vienna, Wien, Austria

Background: By conformational change, the platelet integrins CD41 and CD61 form the glycoprotein IIb/IIIa complex, which serves as inducible receptor for fibrinogen and is essential for thrombus formation. Contradictory, the total amount of these integrins in platelets was reported to be lower in prothrombotic diseases such as lupus anticoagulants (LA), COVID-19, patients and lung cancer. In addition, the platelets of the latter two also showed a lower fibrinogen-binding capacity, which is still unknown for LA.

Aims: This study aimed to quantify the basal and activated platelet surface levels of integrins CD41 and CD61 and their affinity to bind fibrinogen (via PAC-1) in patients with LA compared to healthy control individuals.

Methods: Six patients with persistent LA and a thrombosis history (LA/TE+) and six matched healthy controls were included (Table1). Blood was drawn into CTAD blood tubes. Basal and ADP-activated [15 µM] surface amounts of CD41, CD61 and the activated CD41/CD61 complex were measured from platelet-rich plasma using flow cytometry.

Results: Basal levels of CD41 (+1.31; P=0.041) and CD61 (+1.38; P=0.008) were increased in LA/TE+ patients compared to healthy controls (Figure 1A-1B). However, after ADP activation, the increase of platelet surface levels of CD61 and CD41 was more substantial in healthy controls compared to the LA/TE+ patients (Figure 1A-1B). Likewise, ADP-induced binding affinity to fibrinogen was stronger upregulated in healthy controls, compared to LA/TE+ patients (Figure 1C).

Conclusion(s): The elevated basal levels of the surface integrins CD41 and CD61 indicate a higher activation state of platelets in LA/TE+ patients. The reduced ADP-induced upregulation may be related to the lower total available amount of these glycoproteins in their platelets. These observations support the assumption of permanently activated and “exhausted” platelets that might contribute to the prothrombotic phenotype in patients with persistent LA.