Quasi-Static Acoustic Tweezing Thromboelastometry

Abstract

Acutely unwell patients often develop coagulopathy due to depletion of both pro- and anti-coagulants. They are at high risk of both bleeding and thrombotic complications and require monitoring of their coagulation status. Available contact assays for blood plasma and whole blood coagulation have low predictive power in patients with coagulopathy or take a significant amount of time to obtain diagnostic data. We have developed quasi-static acoustic tweezing thromboelastometry (QATT) as a noncontact method for real-time assessment of blood coagulation. In our method, 4-5 microliter human blood drops are levitated in air by the acoustic radiation force. The sample drop location and deformation are controlled by quasi-statically changing the acoustic pressure. Time-dependent rheological properties of the samples (e.g. sample elasticity) are determined from digital images at each pressure level. Results of our study show that increasing elasticity during coagulation causes blood drops to deform less, leading to steeper deformation/location curves. By extracting a linear regime slope, the samples exhibit a unique slope profile (tweezograph) as they begin to clot. By using tweezographs, we were able to measure the reaction time, coagulation rate and maximum clot stiffness. The exposure of whole blood samples to pro- or anti-coagulants led to significant changes in tweezographs within 10 minutes of sample tweezing, thus allowing detection of hyper- or hypo-coagulable states. Similarly, we detected significant changes between low, normal, and high fibrinogen level control plasma samples, which points out to the ability of our method to measure the fibrinogen level. We demonstrated that QATT can rapidly yield information about coagulation properties of human blood and requires a very small sample volume (∼4 microliter). The advantages of small sample size, non-contact and rapid measurement make this technique desirable for real-time monitoring of blood coagulation in acutely unwell patients.