PB0163 - In vitro monitoring of anti-coagulation therapy in whole blood using magnetic nanoparticles and susceptometry

Background: Alternating Current (AC) susceptometers measure an intrinsic property of magnetic nanoparticles called imaginary magnetic susceptibility (χ’’). Imaginary 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, magnetic susceptometry could be used to measure blood coagulation, clot compaction and changes in internal viscosity of clots in real-time.

Aims: To assess whether AC susceptometry can be used as a measure of whole blood coagulation and to assess the effect of anti-coagulant drugs in altering this response in vitro.

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 bivalirudin, heparin or their carriers. After recalcification and stimulation with 125 µM adenosine diphosphate, susceptibility measurements of the blood samples were performed every 70 seconds for 22-minutes at 400 Hz.

Results: AC susceptibility measurements in control samples (Figure 1AB-Black dots) showed a decrease in the imaginary magnetic susceptibility χ’’ over time, reaching a slowly-declining baseline within 5 minutes of stimulation. These observations are consistent with a rapidly diminishing mobility of IONPs over time due to blood coagulation and clot compaction. In contrast, the rapid fall in imaginary susceptibility over time seen in the control samples is significantly slowed in a dose-dependent manner when blood is pre-treated with bivalirudin (Figure 1A) and heparin (Figure 1B). This is consistent with reduced immobilisation of the IONPs within the clot due to the slowing of blood coagulation.

Conclusion(s): AC susceptometry measurements could provide an improved method to monitor blood coagulation and changes in the physical structure of blood clots. This could result in novel susceptibility-based assays for diagnosis of bleeding disorders and monitoring efficacy of anti-thrombotic drugs in patients.