Detecting Alterations in Fractal Fibrin Patterns using Light Microscopy

Abstract

Fibrin is produced from the polymerization of fibrinogen at the completion of the coagulation cascade. Alterations in the structure and pattern of fibrin in plasma clots have been associated with various disease states such as pulmonary embolism, myocardial infarction, and hemophilia. Assessing these structural changes often requires confocal microscopy with fluorescently labeled fibrinogen or electron microscopy. Here, we demonstrate a novel method whereby pathophysiological alterations in fibrin patterns can be detected using light microscopy. Images of plasma clots from the partial thromboplastin time test were analyzed for alterations in fractal patterns using The Workflow of Matrix Biology Informatics. Factor VIII and Factor IX deficiencies showed significant changes in lacunarity, branchpoints, and total pattern area. We also detected significant changes in fibrin patterns altered by hyperglycemia, a known risk factor for thrombosis and embolisms. This work has direct clinical relevance as it utilizes readily available technology that can be applied in the clinical laboratory to screen patient samples for fibrin alterations when clotting time tests are prolonged. This diagnostic information could be utilized in the identification of various diseases that affect blood clot formation.