Microfluidics contrasted to thrombelastography: perplexities in defining hypercoagulability

Abstract

Background: Elevated clot strength (maximum amplitude [MA]) measured by thrombelastography (TEG) is associated with thrombotic complications. However, it remains unclear how MA translates to thrombotic risks, as this measurement is independent of time, blood flow, and clot degradation. We hypothesize that under flow conditions, increased clot strength correlates to time-dependent measurements of coagulation and resistance to fibrinolysis.

Materials and methods: Surgical patients at high risk of thrombotic complications were analyzed with TEG and total thrombus-formation analysis system (T-TAS). TEG hypercoagulability was defined as an r <10.2 min, angle >59, MA >66 or LY30 <0.2% (based off of healthy control data, n = 141). The T-TAS AR and PL chips were used to measure clotting at arterial shear rates. T-TAS measurements include occlusion start time, occlusion time (OT), occlusion speed (OSp), and total clot generation (area under the curve). These measurements were correlated to TEG indices (R time, angle, MA, and LY30). Both T-TAS and TEG assays were challenged with tissue plasminogen activator (t-PA) to assess clot resistance to fibrinolysis.

Results: Thirty subjects were analyzed, including five controls. TEG-defined hypercoagulability by MA was detected in 52% of the inflammatory bowel disease/cancer patients; 0% was detected in the controls. There were no TEG measurements that significantly correlated with T-TAS AR and PL chip. However, in the presence of t-PA, T-TAS AR determined OSp to have an inverse relationship with TEG angle (-0.477, P = 0.012) and LY30 (-0.449, P = 0.019), and a positive correlation with R time (0.441 P = 0.021). In hypercoagulability determined by TEG MA, T-TAS PL had a significantly reduced OT (4:07 versus 6:27 min, P = 0.043). In hypercoagulability defined by TEG LY30, T-TAS PL had discordant findings, with a significantly prolonged OT (6:36 versus 4:30 min, P = 0.044) and a slower OSp (10.5 versus 19.0 kPa/min, P = 0.030).

Conclusions: Microfluidic coagulation assessment with T-TAS has an overall poor correlation with most TEG measurements in a predominantly hypercoagulable patient population, except in the presence of t-PA. The one anticipated finding was an elevated MA having a shorter time to platelet-mediated microfluidic occlusion, supporting the role of platelets and hypercoagulability. However, hypercoagulability defined by LY30 had opposing results in which a low LY30 was associated with a longer PL time to occlusion and slower OSp. These discordant findings warrant ongoing investigation into the relationship between clot strength and fibrinolysis under different flow conditions.

Keywords: Hypercoagulable; Microfluidics; Platelet; T-TAS; TEG; Thrombelastography.