Scientific Paper: Elemental Characterisation of Anomalous Intravascular Casts Reveals an Abnormal Biochemical Matrix

Paper Two:

Elemental Characterisation of Anomalous Intravascular Casts Reveals an Abnormal Biochemical Matrix

Paper two revealed the clots have a bizarre chemical fingerprint. They are depleted in sulphur (a key marker of protein) and enriched in phosphorus, a composition impossible for a normal, protein-dominant fibrin clot. This indicates a hybrid organic-inorganic matrix, not a simple blood clot. 

Abstract:

In the first paper of this trilogy, anomalous intravascular casts (AICs) were established as a discrete morphological–histological phenotype distinct from conventional antemortem thrombi and ordinary postmortem clots. While those findings demonstrated that AICs form coherent, lumen-conforming intravascular structures under conditions of active blood flow, morphology and histology alone cannot determine the biochemical nature of the matrix from which such structures are formed. Blinded, multi-site elemental analyses were performed on anomalous intravascular casts using inductively coupled plasma mass spectrometry (ICP-MS). Elemental compositions were benchmarked against whole-blood reference values and first-principles stoichiometric expectations derived from fibrinogen to assess compatibility with canonical fibrin-based clot biochemistry. AICs exhibited reproducible, non-physiological elemental ratios characterized by marked sulfur depletion, relative phosphorus enrichment, and imbalance within bulk elemental relationships. These compositional features are incompatible with protein-dominant fibrin matrices and could not be explained by simple fibrin overload, cellular aggregation, or classical coagulation artifacts. The elemental composition of anomalous intravascular casts is inconsistent with canonical thrombus biochemistry and supports the presence of a non-canonical intravascular matrix. These findings independently corroborate the structural conclusions of the first paper in this series and establish the need for protein-level analysis to identify the molecular constituents underlying this anomalous material, which is addressed in the final paper of this trilogy.

Also available at: https://www.preprints.org/manuscript/202601.2149