The dynamics of D-dimer formation. Thrombin converts plasma fibrinogen to fibrin monomers. Thrombin then remains associated with fibrin and activates factor XIII, which circulates bound to fibrinogen. Factor XIIIa is formed as fibrin polymerizes and continues after fibrin has formed an insoluble gel. The D-dimer antigen is formed by the sequential action of thrombin, FXIIIa, and plasmin. Plasmin releases D-dimer antigen from fibrin polymers before and after fibrin gels. Thus, D-dimer antigen as detected by commercially available assays can either be derived from the soluble fibrin polymers before their uptake in the clot or be the product of plasmin cleavage of the fibrin clot.