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 detectedin52% 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.

The use of viscoelastic hemostatic tests in pregnancy and puerperium: review of the current evidence ‐ communication from the Women's Health SSC of the ISTH

“…We also believe that much more attention needs to be given to assessment of hypercoagulability (compared with bleeding) during pregnancy, particularly in placenta‐mediated complications with complex coagulopathies such as preeclampsia, gestational diabetes, or recurrent miscarriage. Indeed, extensive evidence for the effectiveness of TEG/ROTEM in identifying hypercoagulability has been demonstrated in various clinical conditions, including cancer and preeclampsia . TEG/ROTEM applications in hypercoagulability and thrombosis in pregnancy remain to be expanded.…”

Value of Thromboelastography in Judging Abnormal Coagulation Function in Patients with Early Hemorrhagic Shock

“…MA was used to assess the intensity of blood clots. Due to platelet count and function, MA value was associated with platelet action, and elevated MA value suggested that blood was hypercoagulable [6]. Studies have shown that the MA value and the probability of thrombosis have higher sensitivity and specificity, the MA value increases, and the probability of thrombosis increases significantly [7].…”

Scalable manufacture of a disposable, storage-stable eight-channel microfluidic device for rapid testing of platelet, coagulation, and drug function under whole blood flow

“…This assay has the advantage of operating at physiological shear rates and in an open system, but generates only a single clot per chip, has shown a poor correlation with direct oral anti-coagulant (DOAC) doses, and has poor agreement with the more established thromboelastographic methods. 23,24 This study used validated flow experiments and reagents from PDMS microfluidic techniques and deployed an injection molded chip to create a versatile technology for medical professionals at the bedside. [1][2][3]7,9,19 A POC microfluidic device needs to (1) utilize small volumes (<1 ml) of whole blood, (2) have a scalable production method, (3) be simple to prime and operate by non-expert users, (4) retain uniform flow behavior across all test conditions, (5) be storage stable in a prepared state, and (6) have a total experimental footprint suitable for benchtop use.…”