TRIDENT Case Card: Sickle Cell Disease HbS polymerisation as a boundary-driven coherence failure in erythrocyte function

Sickle cell disease (SCD) is a monogenic disorder caused by a single point mutation in the β-globin gene (Glu6Val) that enables deoxygenated haemoglobin S (HbS) to polymerise under hypoxic conditions. Polymer formation drives erythrocyte stiffening, vaso-occlusive crisis, haemolysis, and progressive organ damage. The molecular mechanism linking mutation to polymer fibre assembly is structurally resolved. This case card applies the TRIDENT diagnostic framework (Bulk Lock, Boundary Flow, Constraint Field, Coherence Dependency) to evaluate mechanistic closure in SCD. Gates 1-3 pass robustly, supported by crystallographic structure, natural hereditary persistence of fetal haemoglobin (HPFH), hydroxyurea randomised…