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Increased expression of protein disulfide isomerase A1 on platelet surface in lupus anticoagulant-associated thrombosis

1Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria, Vienna, Wien, Austria, 2Division of Haematology and Haemostaseology, Medical University of Vienna, Vienna, Austria, Vienna, Wien, Austria, 3Department of Medicine I, Clinical Division of Haematology and Haemostaseology, Medical University of Vienna, Vienna, Wien, Austria, 4Medical University of Vienna, Vienna, Austria, Vienna, Wien, Austria

Abstract Number: VPB0420

Meeting: ISTH 2022 Congress

Theme: Venous Thromboembolism » Antiphospholipid Syndrome

Background: Antiphospholipid antibody syndrome (APS) is an autoimmune disorder defined by the presence of antiphospholipid antibodies (aPLAs) in combination with the occurrence of venous and/or arterial thromboembolism (TE). Among aPLA positives, the ones who have lupus anticoagulant (LA) are at highest risk of developing thromboembolism (TE). So far, the role of platelets in the pathogenesis of LA+TE+ patients is not fully investigated. In previous platelet proteomic analysis, we discovered that protein disulphide isomerase A1 (PDI A1), a member of the PDI family, was significantly upregulated in platelets and plasma of LA+TE+ patients (Hell et al, Exp Mol Med, 2020,52,66-78). Several studies indicated the association of PDIs and thrombosis formation, however, the exact function of these proteins is not clear yet.

Aims: To investigate the levels of PDI A1 on platelet surface in LA+TE+ patients in comparison to control subjects.

Methods: Platelets from LA positive patients with a history of TE and platelets from age and sex matched healthy controls were analyzed for differences in PDI A1 surface expression in vivo by flow cytometry.

Results: We investigated 21 LA+TE+ patients (67% females, median age: 48 years), all of whom were triple positive (in addition anticardiolipin and anti-ß2-glycoprotein I antibodies) and 21 healthy controls (67% female, median age: 48 years) (Table 1). We found significantly higher levels of PDI A1 on platelet surface in LA+TE+ patients in comparison to healthy individuals (median IQR: LA+TE+ 14.03 (12.41-16.78), controls 11.9 (8.7-17.01), p=0.021) (Figure 1).

Conclusion(s): The meaningful upregulation of PDI A1 on the surface of platelets in LA+TE+ patients together with our previous findings about the prothrombotic platelet proteome in APS patients and enhanced levels of PDI A1 in plasma indicate a role for PDI and a contribution of platelets in thrombotic events in LA positive patients.

Table 1

Demographic and laboratory characteristics of LA+TE+ patients -n=21- and healthy controls -n=21-

Figure 1

Platelet surface PDI A1 expression of LA+TE+ patients -n=21- compared to healthy controls -n=21-.

To cite this abstract in AMA style:

Romer A, Samadi N, Hell L, Ay C, Gebhart J, Pabinger I. Increased expression of protein disulfide isomerase A1 on platelet surface in lupus anticoagulant-associated thrombosis [abstract]. https://abstracts.isth.org/abstract/increased-expression-of-protein-disulfide-isomerase-a1-on-platelet-surface-in-lupus-anticoagulant-associated-thrombosis/. Accessed September 22, 2023.

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