Novel Shear-Activated Nano-Inhibitor of Polyphosphate (SANIPP): A Conceptual Framework for Preventing Thrombosis Without Compromising Hemostasis

This conceptual manuscript presents the Shear-Activated Nano-Inhibitor of Polyphosphate (SANIPP), a novel antithrombotic strategy that selectively neutralizes polyphosphate (PolyP)-driven coagulation amplification under pathological high shear stress, thereby preventing thrombosis while preserving physiological hemostasis. Inspired by established shear-sensitive nanotherapeutics \cite{Korin2012} and PolyP-targeted inhibitors \cite{Mailer2023,Travers2014}, SANIPP comprises microscale aggregates of inhibitor-loaded nanoparticles that dissociate exclusively in stenotic vessels (>100 dyn/cm²). A comprehensive mathematical model of coagulation dynamics, fully reproducible Python implementation (provided herein), sensitivity and uncertainty analyses, and explicit falsifiability criteria validate the framework. Simulations demonstrate substantial selective suppression of thrombin generation in high shear with no effect in low shear. The model establishes explicit falsifiability criteria, defining successful inhibition as a >50% reduction in thrombin generation solely under shear conditions exceeding 80 dyn/cm². This manuscript is entirely self-contained.