A new structural biomarker that quantifies and predicts changes in clot strength and quality in a model of progressive haemodilution

Abstract

Introduction: We investigated the effect of progressive haemodilution on the dynamics of fibrin clot formation and clot microstructure using a novel rheological method. The technique measures clotting time (T_GP), clot strength (G'_GP), and quantifies clot microstructure (d_f) at the incipient stages of fibrin formation. We use computational modelling to examine the relationship between structure and mass, as well as helium ion microscopy (HIM) to compare morphological changes in the fully formed clot to that of the incipient clot.

Methods: This is an in vitro study; 90 healthy volunteers were recruited with informed consent and a 20 ml sample of whole blood obtained from each volunteer. Five clinically relevant dilutions were investigated using 0.9w.v isotonic saline (0, 10, 20, 40 and 60%, n = 18 for each dilution). The rheological method of assessing structural clot changes was compared against conventional coagulation screen and fibrinogen estimation.

Results: Fractal dimension (df) and final clot microstructure both decreased with progressive dilution (significant at a dilution of 20%) with similar relationships observed for final clot characteristics in HIM images. Significant correlations were observed between d_f and G'_GP (clot strength) (0.345, p = 0.02), as well as clotting time (PT: -0.690, p > 0.001; APTT: -0.672, p > 0.001; T_GP: -0.385, p = 0.006).

Conclusions: This study provides new insight into the effects of haemodilution by isotonic saline on clotting time (T_GP), clot strength (G'_GP) and clot microstructure (d_f). Previous studies have attempted to link clot microstructure to clot quality/strength, however this study provides a significant step in quantifying these relationships.

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Identifiers

ORCID for Stuart Boden: orcid.org/0000-0002-4232-1828

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