Comprehensive Coagulation Profiling at the Point-of-Care Using a Novel Laser-Based Approach

Abstract

Delays in identifying internal bleeding are life-threatening, thus underscoring the need for rapid and comprehensive coagulation profiling at the bedside. The authors review a novel optical coagulation profiler that measures several coagulation metrics including prothrombin time, activated clotting time, clot polymerization rate (α-angle), clot stiffness (maximum amplitude), fibrinolysis (LY), and platelet function, using a single multifunctional instrument. The optical profiler is based on the principles of Laser Speckle Rheology that quantifies tissue viscoelasticity from light scattering patterns called laser speckle. To operate the optical profiler, whole blood (40 μL) is loaded into a disposable cartridge, laser speckle patterns are recorded via a camera, and the viscoelasticity of clotting blood is estimated from speckle intensity fluctuations. By monitoring alterations in viscoelastic moduli over time during clot initiation, thrombin generation, fibrin crosslinking, clot stabilization, and LY, global coagulation parameters are obtained within 10 minutes using a drop of whole blood. Clinical testing in over 500 patients to date has confirmed the accuracy of the optical profiler for comprehensively assessing coagulation status against conventional coagulation tests and thromboelastography. Recent studies have further demonstrated the capability to quantify platelet aggregation induced by adenosine diphosphate in a drop of platelet-rich-plasma in the absence of applied shear stress. Together, these studies demonstrate that global coagulation profiling in addition to platelet function may be accomplished using a single multifunctional device. Thus, by enabling rapid and comprehensive coagulation and platelet function profiling at the bedside, the optical profiler will likely advance the capability to identify and manage patients with an elevated risk for hemorrhage.

Viscoelastic Hemostatic Assays: Moving from the Laboratory to the Site of Care—A Review of Established and Emerging Technologies

“…Laser Speckle Rheometry (Figure 9) is a technology being pioneered at the Wellman Center for Photomedicine at Massachusetts General Hospital and Harvard Medical School [35,36]. The technology has applications in a range of areas, including the catheter-based assessment of atherosclerotic plaques.…”

Tutorial on laser speckle rheology: technology, applications, and opportunities

“…59,60 3 Laser Speckle Rheology: Technology Platform LSR is an optical technique that evaluates the viscoelastic properties of biological tissues and biomaterials, without applying an external force, physically contacting the specimen, or using exogenous particles, in a passive, noninvasive approach. [30][31][32][33][34][35][37][38][39][40][41][42][43][44][45][46][61][62][63][64] Laser speckle [ Fig. 1(a)] is a random granular pattern of dark and bright spots that emerges when a highly coherent beam of light, e.g., laser, is backscattered from a particulate material, such as the biological tissue.…”

“…These fluctuations are highly sensitive to particle displacements, and in-turn to the viscoelastic properties of the microenvironment surrounding the particles. [30][31][32][33][34][35][37][38][39][40][41][42][43][44][45][46]64 The optical layout of a bench-top LSR system is shown in Fig. 1(b).…”

“…83 Our lab has developed an LSR-based sensor, termed iCoagLab, that provides a comprehensive profiling of hemostatic function by measuring activated clotting time (ACT), PT, clot rate, clot stiffness, fibrinolysis, all using the same instrument via inexpensive disposables by evaluating a drop of blood. 38,41,43,44,46,64 The instrument [Fig 4(a)] is a miniaturized and customized embodiment of the general LSR platform, featuring a small laser diode to illuminate the sample and a CMOS camera to acquire the speckle patterns. 43,44,46 In unclotted blood, the continuous motion of light scattering red blood cells and platelets undergoing Brownian motion induces rapid temporal speckle intensity fluctuations.…”

Innovations in Thrombosis and Hemostasis: A Glimpse Towards the Future of Diagnostic Analyzers

“…Laser speckle rheology (LSR) is employed to detect clot formation using another novel optical hand-held point-ofcare device that performs several coagulation tests including prothrombin time, activated clotting time, clot polymerization rate (α-angle), clot stiffness, fibrinolysis, and platelet function. 5 As described by Nadkarni, LSR quantifies tissue viscoelasticity from light scattering patterns called laser speckle, using small amounts (40 µL) of whole blood and providing test results within 10 minutes.…”