Forensic Dating of Venous Thromboembolism: Advances in Histological, Immunohistochemical and Molecular Markers

Abstract

Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a major cause of sudden death and a frequent finding in forensic practice. Correctly estimating thrombus age is crucial to reconstruct the temporal relationship among clinical events, therapeutic decisions, and death, and also to distinguish unavoidable complications from possible diagnostic or management errors. This narrative review summarizes current macroscopic, histological, immunohistochemical, and molecular criteria for thrombus dating, integrating evidence from autopsy studies, experimental models, and clinical research. Because of the inherent heterogeneity of thrombi and postmortem changes, classical morphology frequently does not provide sufficiently precise timing, although it does allow a broad distinction between acute, subacute, and chronic thrombi. A more precise temporal characterization has recently been made possible by the introduction of immunohistochemical and molecular markers, such as neutrophils and NETs, macrophage markers, fibrinolytic system components, metalloproteinases, inflammatory cytokines, autophagy markers, aquaporins, and pro-resolving pathways. In order to improve diagnostic accuracy, a combined evaluation of these characteristics seems promising in differentiating clinically relevant time windows (within 3 days, 3–10 days, 10–21 days, and >21 days). Molecular profiling combined with advanced histopathology may eventually enable more consistent and repeatable thrombus dating standards and enhance the forensic assessment of VTE-related fatalities.