Clinical Information

Thrombin, the terminal enzyme of the plasma procoagulant cascade, cleaves fibrinopeptides A and B from fibrinogen, generating fibrin monomer. Fibrin monomer contains D domains on each end of the molecule and a central E domain. Most of the fibrin monomers polymerize to form insoluble fibrin, or the fibrin clot, by repetitive end-to-end alignment of the D domains of 2 adjacent molecules in lateral contact with the E domain of a third  molecule. The fibrin clot is subsequently stabilized by thrombin-activated factor XIII, which covalently cross-links fibrin monomers by transamidation, including dimerization of the D domains of adjacently polymerized fibrin monomers.

The fibrin clot promotes activation of fibrinolysis by catalyzing the activation of plasminogen (by plasminogen activators) to form plasmin enzyme. Plasmin proteolytically degrades cross-linked fibrin, ultimately producing soluble fibrin degradation products of various sizes that include cross-linked fragments containing neoantigenic D-dimer (DD) epitopes. Plasmin also degrades fibrinogen to form fragments X, Y, D, and E. D-dimer immunoassays use monoclonal antibodies to DD neoantigen and mainly detect cross-linked fibrin degradation products, whereas the fibrino(geno)lytic degradation products X, Y, D, and E and their polymers may be derived from fibrinogen or fibrin. Therefore, the blood content of D-dimer indirectly reflects the generation of thrombin and plasmin, roughly indicating the turnover or activation state of the coupled blood procoagulant and fibrinolytic mechanisms.