Global assays of hemostasis

Abstract

Purpose of review: There exists an imbalance between our understanding of the physiology of the blood coagulation process and the translation of this understanding into useful assays for clinical application. As technology advances, the capabilities for merging the two areas have become more attainable. Global assays have advanced our understanding of the dynamics of the blood coagulation process beyond end point assays and are at the forefront of implementation in the clinic.

Recent findings: We will review recent advances in the main global assays with a focus on thrombin generation that have potential for clinical utility. These assays include direct (thrombogram, whole blood, purified systems) and indirect empirical measures of thrombin generation (thromboelastography) and mechanism-based computational models that use plasma composition data from individuals to generate thrombin generation profiles.

Summary: Empirical thrombin generation assays (direct and indirect) and computational modeling of thrombin generation have greatly advanced our understanding of the hemostatic balance. Implementation of these types of assays and visualization approaches in the clinic will potentially provide a basis for the development of individualized patient care. Advances in both empirical and computational global assays have made the goal of predicting precrisis changes in an individual's hemostatic state one step closer.

Figure 1

Standard clotting assays. Both the prothrombin time (utilizing the extrinsic pathway) and activated partial thromboplastin time (utilizing the intrinsic pathway) assays are ideal for detecting gross coagulation defects. However, since the endpoint of these assays is the fibrin clot, these assays exclude over 95% of the thrombin generated in the complete reaction.

Figure 2

Global empirical thrombin assays. A) Thrombin generation assay in plasma. B) Purified protein-based synthetic coagulation proteome compared to the respective computational model. C) Thromboelastography. D) Whole blood assay. E) Computational analysis of the effect of equivalent doses of rivaroxaban on different individual profiles. F) Extraction of the thrombin parameters from the previous data into a unique four parameter graph displaying maximum rate (x-axis), maximum level (color), clot time (y-axis) and total thrombin generated (size). Reprinted with permission from [18].