Blood flow and mass transfer regulation of coagulation

Abstract

Blood flow regulates coagulation and fibrin formation by controlling the transport, or mass transfer, of zymogens, co-factors, enzymes, and inhibitors to, from, and within a growing thrombus. The rate of mass transfer of these solutes relative to their consumption or production by coagulation reactions determines, in part, the rate of thrombin generation, fibrin deposition, and thrombi growth. Experimental studies on the influence of blood flow on specific coagulation reactions are reviewed here, along with a theoretical framework that predicts how flow influences surface-bound coagulation binding and enzymatic reactions. These flow-mediated transport mechanisms are also used to interpret the role of binding site densities and injury size on initiating coagulation and fibrin deposition. The importance of transport of coagulation proteins within the interstitial spaces of thrombi is shown to influence thrombi architecture, growth, and arrest.

Flow chamber and microfluidic approaches for measuring thrombus formation in genetic bleeding disorders

“…41 Differences in fibrin surface coverage and thrombus size are most pronounced at venous and moderate arterial shear rates because there is less dilution of coagulation products by blood flow. 62 Similar observations of diminished thrombus volume were reported on type I collagen using thrombin inhibitors and hemophilia A samples. 67 The T-TAS® system was used to evaluate thrombus formation on collagen-TF surfaces in blood from a FVIII −/− mouse and with human blood treated with an anti-FIXa aptamer.…”

“…61 Despite these challenges, the motivation for measuring thrombus formation in hemophilia blood under flow stems from the well-documented regulation of coagulation by blood flow and the role of fibrin in establishing the mechanical properties of thrombi. 62–64 …”

A Microfluidic Model of Hemostasis Sensitive to Platelet Function and Coagulation

“…The mechanisms of platelet adhesion and aggregation and the relative role of platelet function and coagulation are regulated by forces and mass transfer limitations imposed on a growing thrombus by blood flow. 10,35 …”

Regulation of Platelet Activation and Coagulation and Its Role in Vascular Injury and Arterial Thrombosis

“…Studies have shown that individual reactions within the coagulation cascade can switch from being reaction-to transport-limited depending on the local conditions 69 . Limited transport increases the residence time of solutes in the platelet mass, which translates into reduced generation of new thrombin, and at the same time increased biological activity of locally trapped thrombin.…”