DEGRADATION OF FIBRINOGEN AND CROSS-LINKED FIBRIN BY HUMAN NEUTROPHILELASTASE GENERATES D-LIKE FRAGMENTS DETECTED BY ELISA BUT NOT LATEX D-DIMER TEST

Recently, we observed that D-dimers are degraded by human neutrophil e lastase (HNE) into two D-like fragments, reacting with the monoclonal antibody in an ELISA D-dimer test but not reacting with the correspond ing 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. Degrad ation of fibrinogen, both by plasmin and HNE, resulted in D- and D-lik e fragments, respectively, detected by the ELISA D-dimer test. Degrada tion 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-d imers detected by the latex D-dimer test were only observed after degr adation of cross-linked fibrin with plasmin. We conclude that during l ysis 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 ELI SA D-dimer test may therefore be used to detect fibrin and fibrinogen degradation products generated by the combined action of plasmin and H NE in sepsis and other conditions with increased HNE activity, while t he latex D-dimer test may be used to detect plasmin derived intact D-d imers. (C) 1998 Elsevier Science Ltd.