OC 17.1 - AC Magnetic Susceptibility: A New Nanotechnological Tool for ex vivo Monitoring Coagulation in Whole Blood

Background: Blood clotting disorders consisting of unwanted blood clot formation or excessive bleeding are some of the main causes of death worldwide. However, there are significant limitations in the current methods used to clinically monitoring the dynamics of clot formation in human whole blood ex vivo. Alternating Current (AC) susceptometers measure an intrinsic property of magnetic nanoparticles called AC magnetic susceptibility (χ’’). AC susceptibility reveals variations in mobility and agglomeration of magnetic nanoparticles when these are dispersed in biological tissues such as human blood. By labelling human blood with magnetic nanoparticles, AC magnetic susceptibility could be used to measure blood coagulation, clot compaction and changes in internal viscosity of clots in real-time. (Figure 1AB)

Aims: To assess whether AC susceptometry can be used as a measure of whole blood coagulation.

Methods: AC susceptibility measurements were performed in citrated whole human blood, labelled with iron oxide nanoparticles (IONPs) coated with sucrose, and pre-treated with different concentrations of anticoagulants. After recalcification and activation susceptibility measurements of the blood samples were performed in two different modes: spectral (Figure 1C) and in single frequency (Figure 1D).

Results: AC susceptibility measurements in control samples (Figure 2) showed a decrease in the out-of-phase component of magnetic susceptibility χ’’ reaching a slowly-declining baseline within 5 minutes. These observations are consistent with a rapidly diminishing mobility of magnetic nanoparticles over time due to blood coagulation. In contrast, the rapid fall in the out-of-phase component of susceptibility over time seen in the control samples is significantly slowed in a dose-dependent manner when blood is pre-treated with rivaroxaban (Figure 2). This is consistent with reduced immobilisation of the IONPs within the clot due to the slowing of blood coagulation.

Conclusion(s): AC susceptibility measurements could provide an improved method to monitor blood coagulation and changes in the physical structure of blood clots.