Evaluating caplacizumab's potential to mitigate thrombosis risk in aortic valve stenosis: a microfluidic and computational approach

Aortic valve stenosis is a progressive cardiovascular disease associated with increased thrombotic risk due to abnormal blood flow patterns. Current management often culminates in valve replacement surgery, demonstrating the need for less invasive therapeutic options. This study investigates the potential of caplacizumab, a von Willebrand factor (vWF) inhibitor, in mitigating thrombosis risk in a microfluidic model of aortic valve stenosis. We employed a novel microfluidic model simulating the hemodynamics of healthy, moderate, and severe stenotic conditions, complemented by computational fluid dynamics simulations (CFD) and conventional platelet function assays. Microfluidic experiments revealed that shear gradients play a critical role in platelet aggregation, with accumulation intensifying as stenosis severity increased, even under constant peak shear rates. Caplacizumab demonstrated high specificity for vWF-mediated platelet aggregation, significantly inhibiting ristocetin-induced aggregation while not affecting ADP-induced aggregation. At an effective concentration (30 nM), caplacizumab reduced platelet coverage by up to 90% in high shear conditions (4500 s^-1) and effectively mitigated shear gradient-dependent platelet aggregation across all stenotic conditions. These findings highlight caplacizumab's therapeutic potential for thrombosis prevention in patients with aortic valve stenosis, offering a foundation for personalized antithrombotic approaches that could potentially reduce thrombotic complications associated with the disease.