PB1344 - Recurrent thrombosis in antiphospholipid syndrome is associated with endothelial dysfunction as evidenced by raised von-Willebrand factor and reduced vascular hyperaemia index.

Tuesday, June 25, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

JM

James E. Manning, MBChB MSc

Internal medicine trainee & honorary clinical research fellow
Department of Immunity & Inflammation, Centre for Haematology, Imperial College London. London. UK
London, England, United Kingdom

Co-Author(s)

SM

Spencer Mackie

Research Assistant
Department of Haematology, Hammersmith Hospital, DuCane Road, London. UK
London, England, United Kingdom
CP

Charis Pericleous

Versus arthritis career development fellow
National Heart and Lung Institute, London. UK
London, England, United Kingdom
RS

Rocel Saputil

Research assistant
Imperial College London, London. UK
London, England, United Kingdom
MP

Matthew Pickering

Professor of Rheumatology
Department of Immunity & Inflammation, Imperial College London, London. UK
London, England, United Kingdom
Mike Laffan

Professor of haemostasis & thrombosis
Imperial College London, London. UK
London, England, United Kingdom
DA

Deepa J. Arachchillage, MD

Consultant haematologist, honorary senior lecturer & MRC CARP fellow
Department of immunity & inflammation, Centre for Haematology, Imperial College London, London. UK
London, England, United Kingdom

Background: Recurrent thrombosis remains a major issue in patients with antiphospholipid syndrome (APS). Although endothelial dysfunction (ED) is a major contributor to thrombosis, current anticoagulant therapy targets only pro-coagulant plasma proteins rather than ED.

Aims: To assess ED non-invasively using EndoPAT(TM) (Itamar Medical, Israel), which measures endothelial vasodilator function by peripheral arterial tonometry expressed as the log reactive hyperaemia index (lnRHI), and to correlate this with plasma markers of ED in APS patients with recurrent thrombosis.

Methods: In this ethically approved prospective observational study, lnRHI was measured using EndoPAT(TM) and blood samples collected to measure plasma markers of ED following informed written consent in patients with thrombotic APS. Plasma markers were assessed using enzyme linked immunosorbent assay.

Results: A total of 54 patients with thrombotic APS (mean age 53+/-15.3, 63% female) were included in analysis. Of these, 32 had had only one thrombotic event and 22 had multiple thrombotic events whilst off anticoagulation (Table 1). The two groups were comparable for baseline characteristics, cardiovascular risk factors and antiphospholipid antibody profiles. Patients with recurrent thrombotic events had significantly lower lnRHI results consistent with ED (Table 1). von Willebrand Factor (VWF) antigen and ICAM-1 levels were significantly higher in those with recurrent thrombosis, and there was a trend toward higher levels of growth arrest specific protein 6 (Gas6), VCAM-1 and soluble thrombomodulin levels, although these did not reach statistical significance, possibly due to the small sample (Table 1 and Figure 1). VWF level was inversely correlated with lnRHI (r=-0.47, p=0.002). Interestingly, a higher proportion of patients with single thrombotic events were receiving hydroxychloroquine, which may improve endothelial function.

Conclusion(s): Recurrent thrombotic events were associated with ED as evidenced by reduced endothelial vasodilator function and elevated vWF. Prospective validation these data and their response to therapeutic intervention are currently underway. Treatment targeting ED may reduce recurrent thrombosis.