The Impact of Blood Shear Rate On Arterial Thrombus Formation

Abstract

The shear rate and corresponding shear stress have impacts on arterial thrombus formation. In particular, the effects of increasing concentration of platelets at the vessel wall and activation of platelets at this site increase the growth and stability of the thrombi which may result in a fatal narrowing of the arterial lumen. The efficacy of many antithrombotic agents is shear dependent as well. It is apparent that there is a need for a point-of-care device to rapidly monitor the risk for arterial thrombosis and to optimize antithrombotic therapy in vitro. The present review focuses on the essential role of shear rate on arterial thrombus formation in native human blood drawn directly from an antecubital vein.

In vitro studies show synergistic effects of a procoagulant bispecific antibody and bypassing agents

“…The T‐TAS is a microchip‐based flow‐chamber system that measures thrombus formation under physiological blood flow conditions , and was used to confirm the effects of the aPCC–SIA and rFVIIa–SIA combinations. Shear rates of 600 s −1 and 240 s −1 on collagen/TF‐coated AR‐chips were used to represent average‐sized arteries and veins, respectively .…”

In vitro flow based systems to study platelet function and thrombus formation: Recommendations for standardization: Communication from the SSC on Biorheology of the ISTH

“…The subcommittee recommends using direct thrombin inhibitors such as D‐phenylalanyl‐prolyl‐arginyl chloromethyl ketone (P‐Pack; 50 μM) or hirudin (100 U/mL), which are very potent direct thrombin inhibitors allowing one to work with human blood for up to 3 hours and with mouse blood for up to 2 hours. Other anticoagulants, notably trisodium citrate (0.38%), which is broadly available, can be used; however, citrated blood tends to form larger thrombi than the direct thrombin inhibitors as Ca 2+ chelation results in enhanced TxA2 production Flow device: Whole blood flow perfusion over collagen is a very robust and reproducible assay that works with flow devices including parallel plate flow chambers, microslides, commercial devices, and microfluidic channels.…”

“…Other anticoagulants, notably trisodium citrate (0.38%), which is broadly available, can be used; however, citrated blood tends to form larger thrombi than the direct thrombin inhibitors as Ca 2+ chelation results in enhanced TxA2 production. 25…”

Proteolytic processing of platelet receptors

“…Human platelets normally circulate in a resting state and are exposed to shear rates within a physiologic range (~20‐2000 s −1 ) . Platelets may encounter shear rates well beyond 10 000 s −1 under pathologic conditions, for example, in a stenosed atherosclerotic artery or within mechanocirculatory support devices such as left ventricular assist devices (LVADs) or extra‐corporeal membrane oxygenation (ECMO) devices, and become activated and begin to aggregate.…”

“…Platelets may encounter shear rates well beyond 10 000 s −1 under pathologic conditions, for example, in a stenosed atherosclerotic artery or within mechanocirculatory support devices such as left ventricular assist devices (LVADs) or extra‐corporeal membrane oxygenation (ECMO) devices, and become activated and begin to aggregate. Shear‐dependent platelet activation is initiated by binding of plasma VWF to platelets primarily through GPIbα, leading to platelet activation, secretion of ADP, and other agonists, and αIIbβ3‐dependent aggregation . Additionally, when exposed to elevated fluid shear stress, metalloproteolytic shedding of GPVI is triggered .…”