Degradation of Fibrinogen and Cross-Linked Fibrin by Human Neutrophil Elastase Generates D-Like Fragments Detected by ELISA but Not Latex D-Dimer Test

Abstract

Recently, we observed that D-dimers are degraded by human neutrophil elastase (HNE) into two D-like fragments, reacting with the monoclonal antibody in an ELISA D-dimer test but not reacting with the corresponding latex D-dimer test. To investigate this in more detail, we studied the degradation of cross-linked fibrin and fibrinogen by plasmin and HNE to see if this resulted in D-fragments or D-like fragments. Degradation of fibrinogen, both by plasmin and HNE, resulted in D- and D-like fragments, respectively, detected by the ELISA D-dimer test. Degradation of cross-linked fibrin by plasmin and HNE also resulted in D- and D-like fragments, which were detected by the ELISA method. Intact D-dimers detected by the latex D-dimer test were only observed after degradation of cross-linked fibrin with plasmin. We conclude that during lysis of cross-linked fibrin as well as fibrinogen by plasmin and HNE, D-fragments, and D-like fragments, detected by the ELISA D-dimer test, are formed. Only during degradation of cross-linked fibrin by plasmin, intact D-dimers, detected by latex D-dimer test, are formed. The ELISA D-dimer test may therefore be used to detect fibrin and fibrinogen degradation products generated by the combined action of plasmin and HNE in sepsis and other conditions with increased HNE activity, while the latex D-dimer test may be used to detect plasmin derived intact D-dimers.