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Poster Networking

Platelets and Megakaryocytes

PB0786 - Mechanisms and Mediators of Stroke in patients with Fibromuscular Dysplasia

Monday, June 24, 2024
13:45 – 14:45 ICT
Room: Exhibition Hall
Background: Fibromuscular Dysplasia (FMD) is a non-atherosclerotic arterial disorder affecting women with stroke through unclear mechanisms. While anti-platelet therapy is recommended for preventing stroke, scientific data on patient outcomes and mechanisms in FMD are absent.

Aims: To determine mechanism of thrombosis in patients with FMD and utilize platelet-derived proteins as stroke predictors in FMD.

Methods: Patients were evaluated for stroke over 10 years in a propensity-matched, weighted manner. Fluorescence-Assisted Cell Sorting (FACS), Light Transmission Aggregometry (LTA) assessed platelet reactivity. Platelet-Derived Microparticles (PMPs) were isolated from by ultracentrifugation. Thrombosis was assessed in isolated platelets (n=22 FMD, n=15 healthy), in platelet-rich-plasma (PRP), platelet-deplete-plasma (PDP, n=15-16), and in whole blood. Fibrin generation kinetics in PDP was assessed. Platelet biomarkers predicting stroke were assessed by Receiver Operator Characteristic (ROC) curves and area under curve (AUC).

Results: Aspirin better protected against stroke than clopidogrel in FMD patients (5% aspirin or 14% clopidogrel vs. 32.1% without, n=1993 patients). By LTA and by FACS agonist stimulation of platelets through receptors P2Y12, thromboxane, GPVI, and PAR1 in FMD showed similar reactivity to healthy conditions and aspirin had no impact. PDPs from patients with FMD were dose-dependently activated by agonists, showing greater alpha granules (surface MFI CD62P 52.1 vs. 33.9, P=0.005) and dense granules (surface MFI CD63 32.9 vs. 24.2, p=0.002) than healthy PDPs. PDPs from FMD patients profoundly activated PRP from healthy persons and increased fibrin generation in PDP. Platelet GP1ba sheared from the surface of platelets in D-flow conditions experienced in arteries FMD. Blood [GP1ba] predicted stroke in FMD (AUC 69%, P=0.005, sensitivity 70% , specificity 66%, n=195 patients) (Figure).

Conclusion(s): In patients with FMD, aspirin protects against stroke without altering platelet reactivity. PMPs in FMD are highly thrombogenic, increasing platelet activation and augmenting fibrin generation. Platelet-derived GP1ba also predicts stroke in patients with FMD.