Formation and elimination of soluble fibrin and D-dimer in the bloodstream

Abstract

Soluble fibrin is composed mainly of desA fibrin and fibrin-ogen oligomers consisting of fewer than 16 monomers partially cross-linked by factor XIIIa. Soluble fibrin cannot stimulate Glu-plasminogen activation by tissue plasmino-gen activator (t-PA); therefore, it may not be a direct pred-ecessor of D-dimer. However, within the microcirculatory system, soluble fibrin oligomers may form microclots. Fibrin microclots stimulate Glu-plasminogen activation by t-PA, a process resulting in the formation of Glu-plasmin. Glu-plasmin dissolves the microclots, forming D-dimer. In normal and pathological blood plasma samples, soluble fibrin levels are substantially higher than those of D-dim-er. Their concentrations in the plasma are also regulated by transendothelial transfer, absorption by blood macro-phages, and binding and internalization with low-density lipoprotein receptors of the cells of the reticuloendothelial system. Therefore, the exact mechanisms of fibrin clots formation and elimination in normal and pathological condi-tions remain unclear. In this study, we reviewed findings on the molecular mechanisms of the formation and dis-solution of fibrin clots, fibrin-dependent activation of Glu-plasminogen by t-PA, and blood plasma behavior in the microcirculatory system. Finally, we proposed a model that explains the relations of D-dimer and soluble fibrin underlying the common and separate mechanisms of their formation and elimination.