Threshold Response of Initiation of Blood Coagulation by Tissue Factor in Patterned Microfluidic Capillaries Is Controlled by Shear Rate

Abstract

Objective— Blood flow is considered one of the important parameters that contribute to venous thrombosis. We quantitatively test the relationship between initiation of coagulation and shear rate and suggest a biophysical mechanism to understand this relationship. Methods and Results— Flowing human blood and plasma were exposed to cylindrical surfaces patterned with patches of tissue factor (TF) by using microfluidics. Initiation of coagulation of normal pooled plasma depended on shear rate, not volumetric flow rate or flow velocity, and coagulation initiated only at shear rates below a critical value. Initiation of coagulation of platelet-rich plasma and whole blood showed similar behavior. At constant shear rate, coagulation of plasma also showed a threshold response to the size of a patch of TF, consistent with our previous work in the absence of flow. Conclusion— Initiation of coagulation of flowing blood displays a threshold response to shear rate and to the size of a surface patch of TF. Combined with the results of others, these results set the range of shear rates that limit initiation of coagulation by small surface areas of TF and by shear activation of platelets. This range fits the relatively narrow range of physiological shear rates described by Murray’s law.