Surface-dependent reactions in blood coagulation and fibrinolysis: beyond procoagulant platelets

The essential biochemical processes of blood coagulation and fibrinolysis during thrombus formation do not occur in the liquid phase but are instead restricted to specific surfaces. The classic example is phosphatidylserine-containing membranes of procoagulant platelets, which can accelerate the membrane-dependent coagulation reactions by several orders of magnitude. However, there is no clear evidence that this acceleration is the only-or even the primary-consequence of the coagulation factors' binding to the procoagulant membranes. Furthermore, other important surfaces have been identified, including fibrin (together with its numerous associated proteins) and phosphate-rich polymers such as platelet-derived polyphosphates and neutrophil extracellular traps. The distribution of these surfaces within a thrombus is non-uniform, forming complex structures at both micro- and macro-scale. This review explores possible hypotheses regarding their physiological and pathological roles: modulation of the reaction kinetics; regulation of transport processes depending on the rheological microenvironment of the thrombus; integration of coagulation, platelet activity, fibrinolysis, and tissue repair; and control of clot mechanical properties. Elucidating and validating these mechanisms may provide new insights into the development of therapeutic and diagnostic strategies.