Background: Patients with the antiphospholipid syndrome (APS) are at high risk of developing venous and arterial thromboembolism. The role of platelets in the pathogenesis of these prothrombotic conditions is not yet fully understood. Platelet proteome analysis showed protein abundance changes of platelets in patients with APS indicating a causative role of platelets in the development of thrombosis in APS. Additional studies have shown that antiphospholipid antibodies interact with platelets, leading to platelet activation and aggregation.

Aims: The aim was to gain deeper insights into the role of platelets in the APS by investigating differences in platelet activation and responsiveness between patients with APS and healthy controls.

Methods: Platelets from 33 patients with APS (81.8% females, median age: 47 years, interquartile range (IQR): 39-50.5) and 33 healthy controls (81.8% female, median age: 48 years, IQR: 35-53.5) were analysed for differences in P-selectin and PAC-1 (activated glycoprotein IIb/IIIa) positivity (%) and surface expression of P-selectin and PAC-1 (mean fluorescence intensity (MFI)) in vivo and response to ex vivo stimulation with different agonists by whole blood flow cytometry.

Results: Increased baseline but few significant changes to ex vivo stimulation in platelet surface expression of p-selectin (Figure 1A) and PAC-1 (Figure 2A) were detected in patients with APS compared to controls. No difference of baseline p-selectin and PAC-1 positivity could be found, however, platelets from patients with APS were less reactive to ex vivo stimulation with agonists measured on P-selectin (Figure 1B) and PAC1 (Figure 2B) positive platelets.

Conclusions: Patients with APS expose increased baseline platelet activation but decreased platelet reactivity, presumably as a consequence of pre-activation. Together with our previous findings that patients with APS have an altered “prothrombotic” platelet proteome (Hell et al. Exp Mol Med, 2020), the present results support the hypothesis that platelets are involved in thrombotic complications in patients with APS.

[Figure 1: Surface expression of P-selectin in patients with APS compared to healthy controls]

[Figure 2: Surface expression of PAC1 in patients with APS compared to healthy controls]

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/increased-baseline-platelet-activation-and-decreased-platelet-reactivity-in-patients-with-the-antiphospholipid-syndrome/