Principles of Dielectric Blood Coagulometry as a Comprehensive Coagulation Test

Abstract

Dielectric blood coagulometry (DBCM) is intended to support hemostasis management by providing comprehensive information on blood coagulation from automated, time-dependent measurements of whole blood dielectric spectra. We discuss the relationship between the series of blood coagulation reactions, especially the aggregation and deformation of erythrocytes, and the dielectric response with the help of clot structure electron microscope observations. Dielectric response to the spontaneous coagulation after recalcification presented three distinct phases that correspond to (P1) rouleau formation before the onset of clotting, (P2) erythrocyte aggregation and reconstitution of aggregates accompanying early fibrin formation, and (P3) erythrocyte shape transformation and/or structure changes within aggregates after the stable fibrin network is formed and platelet contraction occurs. Disappearance of the second phase was observed upon addition of tissue factor and ellagic acid for activation of extrinsic and intrinsic pathways, respectively, which is attributable to accelerated thrombin generation. A series of control experiments revealed that the amplitude and/or quickness of dielectric response reflect platelet function, fibrin polymerization, fibrinolysis activity, and heparin activity. Therefore, DBCM sensitively measures blood coagulation via erythrocytes aggregation and shape changes and their impact on the dielectric permittivity, making possible the development of the battery of assays needed for comprehensive coagulation testing.

Novel measurements of blood coagulability for assessing the risk of thrombosis

“…Recently, a dielectric blood coagulometry (DBCM) was invented for the evaluation of blood coagulability [13,14]. We investigated whether the DBCM could detect hypo-and hypercoagulability in clinical samples.…”

“…In general, the adequate frequency to measure the permittivity changes is determined based on the size, structure, and content of the objectives. A comparison between blood with and without coagulation revealed that the permittivity changing at 10 MHz represented the aggregation of red blood cells [13,15]. Then we calculated the derivative of the temporal change in the permittivity, and the end of acceleration time (EAT) was established as a whole blood coagulation index [15].…”

ClotChip: A Microfluidic Dielectric Sensor for Point-of-Care Assessment of Hemostasis

“…In fact, DS in the MHz-range has been previously used to determine the properties of blood cellular components [20], [21] and, in particular, is shown to be sensitive to red blood cell (RBC) aggregation and deformation [22]–[24], two critical processes involved in blood coagulation [25]. DS to assess the blood coagulation process is termed dielectric coagulometry , and while early work on dielectric coagulometry revealed sensitivity to both clotting time and platelet activity [26]–[28], this technique has been restricted to studies using laboratory-based benchtop measurement equipment and >100μL-volume samples [29]-[31]. …”

Effects of standard coagulant agents on the dielectric properties of fresh human blood

“…Another application of dielectric properties of blood is dielectric coagulometry. It can assess platelet function, fibrin formation, fibrinolysis and the anticoagulant effect of heparin [4]. Further, the dielectric response of blood can be used to estimate the venous thrombosis risk [5] which is the third cause of excess mortality in U.S. hospitals [6].…”