PB0796 - Lupus Anticoagulant-positive Patients with Thrombosis History have Altered Glycoprotein IIbIIIa Levels

Monday, June 24, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Theresa Schramm, MSc

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

Co-Author(s)

FH

Felicia Hsu

PhD Student
Institute of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna
Vienna, Wien, Austria
AS

Anahita Sedighi

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

Waltraud Schrottmaier

Senior Scientist/Post-Doc
Institute of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, 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
MZ

Maria Zellner

Assoc. Professor
Institute of Vascular Biology and Thrombosis Research, Centre for Physiology and Pharmacology, 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: The glycoprotein IIbIIIa complex (integrins CD41 and CD61) undergoes a conformational change during platelet activation, facilitating fibrinogen binding, platelet aggregation, and thrombus formation. Despite lower reported levels of these integrins in prothrombotic conditions like COVID-19 and lung cancer patients, their role in lupus anticoagulant (LA)-associated thrombosis and fibrinogen-binding capacity remains unclear.

Aims: To measure platelet activation in LA patients with (LA+TE+) and without (LA+TE-) thrombosis history compared to age- and sex-matched healthy controls (HC).

Methods: Patients and HC were selected from the Vienna Lupus Anticoagulant and Thrombosis study (EC1268/2014) and had to be free of antiplatelet drugs. Surface levels of CD41, CD61, and CD62P, and fibrinogen binding to the activated CD41/CD61 complex were assessed from platelet-rich plasma before and after addition of ADP (c=15 µM) using a PAC-1 antibody.

Results: Twenty LA+TE+, 10 LA+TE- patients and 30 HCs were investigated (Tab.1). LA+TE+ patients, but not LA+TE-, exhibited significantly increased basal CD41 (+24%, p=0.026) and CD61 (+18%, p=0.018) levels compared to HCs (Fig.1A-B). Upon activation with ADP, CD41 and CD61 expression increased across all three groups, with a smaller increase of CD41 in LA+TE+ compared to HCs (8% and 13%, p=0.038), but similar in LA+TE- and HC (11%, p=0.450). A similar trend was observed for CD61. No differences in CD62P and fibrinogen affinity were observed before and after ADP activation in LA+TE+ or LA+TE- patients compared to HCs (Figure 1C-1D).

Conclusion(s): Platelet activation was increased in LA+TE+ patients, as evidenced by increased basal CD41 and CD61, which was not observed in LA+TE- patients. The dampened ADP-induced upregulation may be linked to the lower total glycoprotein availability in the platelets of LA+TE+ patients. These findings suggest that persistently activated and “exhausted” platelets may contribute to the prothrombotic phenotype in patients with persistent LA, according to previous observations in various cancers.