Convergent Evidence for a Distinct Intravascular Matrix: Integrated Morphological, Elemental, and Proteomic Analysis of Anomalous Intravascular Casts

Background: Anomalous intravascular casts (AICs) are elongated, lumen-conforming intravascular structures increasingly reported since early 2021. Their unusual elasticity, persistence, and resistance to fragmentation distinguish them from both ordinary postmortem clots and conventional antemortem thrombi, raising the possibility that they represent a distinct, previously unrecognised intravascular phenomenon.

Methods: We performed an integrated analysis of AICs across three independent analytical domains: morphology/histology, elemental composition, and proteomic architecture. Gross and histological examinations, elemental analysis by inductively coupled plasma mass spectrometry (ICP-MS), and proteomic profiling by HPLC-MS/MS were conducted using blinded analytical workflows.

Results: Histological examination demonstrated a reproducible structural phenotype characterized by elongated branching casts, marked elastic resilience, dense fibrinous architecture, sparse cellular inclusion, and regionally restricted Lines of Zahn,. indicating at least partial formation under active blood flow. ICP-MS revealed a reproducible elemental profile incompatible with a conventional fibrin-dominant clot matrix, including sulfur depletion relative to theoretical fibrinogen stoichiometry and relative phosphorus enrichment. These findings indicate that the matrix cannot be explained by fibrin(ogen) alone. Proteomic analysis identified 541 human proteins, with dominance of fibrin-family components in markedly abnormal proportions. Fibrinogen chains were present in a non-physiological mean ratio of approximately 1:7:3 (alpha:beta:gamma), while plasminogen abundance was extremely low, suggesting impaired intrinsic fibrinolytic potential.

Conclusions: Structural, elemental, and proteomic findings converge on a coherent interpretation that AICs are not adequately explained as variants of ordinary postmortem clots or conventional thrombi. Rather, they represent a distinct intravascular matrix characterised by non-conventional fibrin organisation and altered biochemical composition.

Keywords: Anomalous intravascular casts, histology, morphology, fibrin, vascular pathology, postmortem pathology, thrombus structure, fibrinous casts