Feeling the Force: Measurements of Platelet Contraction and Their Diagnostic Implications

Abstract

In addition to the classical biological and biochemical framework, blood clots can also be considered as active biomaterials composed of dynamically contracting platelets, nascent polymeric fibrin that functions as a matrix scaffold, and entrapped blood cells. As platelets sense, rearrange, and apply forces to the surrounding microenvironment, they dramatically change the material properties of the nascent clot, increasing its stiffness by an order of magnitude. Hence, the mechanical properties of blood clots are intricately tied to the forces applied by individual platelets. Research has also shown that the pathophysiological changes in clot mechanical properties are associated with bleeding and clotting disorders, cancer, stroke, ischemic heart disease, and more. By approaching the study of hemostasis and thrombosis from a biophysical and mechanical perspective, important insights have been made into how the mechanics of clotting and the forces applied by platelets are linked to various diseases. This review will familiarize the reader with a mechanics framework that is contextualized with relevant biology. The review also includes a discussion of relevant tools used to study platelet forces either directly or indirectly, and finally, concludes with a summary of potential links between clotting forces and disease.

Blood Clot Phenotyping by Rheometry: Platelets and Fibrinogen Chemistry Affect Stress-Softening and -Stiffening at Large Oscillation Amplitude

“…Other platelets that come along with the blood flow bind to the nascent platelet layer via their α IIb β 3 integrins, either by direct cell–cell contact, or mediated by fibrin(ogen) bridges. The circulating platelets are activated by, e.g., serotonin, thromboxane A 2 and adenosine diphosphate (ADP) released from adhering platelets [ 5 , 7 ], and form a plug with distinct hierarchy [ 8 , 9 ]. Much of this plug contains tightly aggregated platelets within a fibrin fiber meshwork of varying density.…”

“…Much of this plug contains tightly aggregated platelets within a fibrin fiber meshwork of varying density. There can be areas of less activated platelets around this core as well as intervening transition regions [ 7 ]. Numerical simulation has shown that outer parts of the clots can be detached by the RBCs that shear along the plug surface [ 5 ], whereas the dense core remains stable.…”

Highlights of Research in Congenital Cardiac Anesthesia: Summary of Selected Abstracts From the 2020 Congenital Cardiac Anesthesia Society Annual Meeting

“…These platelet nanomechanics of contraction can be measured by cytometry. 1 The authors demonstrated that cardiopulmonary bypass (CPB) significantly lowers platelet contraction force in neonates, which was then associated with increased transfusion requirements. Transfusion of donor platelets restored the platelet contraction force and may reflect restoration of hemostasis.…”

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

“…Williams et al describe several analyzers that are already commercially available, and their ability to assess platelet contractile forces. 9 In development stages, the platelet contraction cytometer is a small device that can assess platelet contractile forces, and preliminary studies suggest that it may identify some patients with a bleeding tendency that cannot otherwise be identified by existing laboratory tests. 9 Next in this issue, Silva and Grabowski take the reader on a tour of platelet function tests as available in the past and present, and also potentially in the future, including a novel microfluidic device in part aimed to assess patients who have mildly low von Willebrand factor (VWF), distinguishing those who are clinically symptomatic versus asymptomatic.…”

“…9 In development stages, the platelet contraction cytometer is a small device that can assess platelet contractile forces, and preliminary studies suggest that it may identify some patients with a bleeding tendency that cannot otherwise be identified by existing laboratory tests. 9 Next in this issue, Silva and Grabowski take the reader on a tour of platelet function tests as available in the past and present, and also potentially in the future, including a novel microfluidic device in part aimed to assess patients who have mildly low von Willebrand factor (VWF), distinguishing those who are clinically symptomatic versus asymptomatic. 10 Emani then reviews the utility of automated digital microfluidics in coagulation testing, with this technology feasibly enabling the performance of up to 12 different tests at once on < 50 µL whole blood using small electric fields to manipulate droplets of fluid on a printed circuit board.…”