Elevated concentrations of cross-linked fibrin degradation products in plasma. An early marker of gram-negative bacteremia.

PURPOSE Because coagulant and fibrinolytic activity are increased by endotoxin, we hypothesized that concentrations of cross-linked fibrin degradation products, sensitive markers of plasmin activity, would be increased in patients with Gram-negative bacteremia. PATIENTS AND METHODS Cross-linked fibrin degradation products were measured with an enzyme-linked immunosorbent assay (ELISA) based on a monoclonal antibody specific for cross-linked fibrin degradation products, and with a novel, semiquantitative hemagglutination assay based on the same antibody coupled to FAB' fragments from a monoclonal antibody against a universal red blood cell antigen. Blood samples were obtained from 100 consecutive emergency department patients evaluated for sepsis. RESULTS Blood cultures were positive in 21 percent of the patients, 75 percent (12/21) with Gram-negative organisms. Elevations of cross-linked fibrin degradation products (normal < 200 ng/ml) were measured by ELISA in all patients (12/12) with Gram-negative bacteremia. The hemagglutination assay was positive in ten of these. Detectable increases in fibrinolytic activity occurred in all patients with Gram-negative bacteremia, even in the absence of clinical signs or laboratory evidence of sepsis or disseminated intravascular coagulation. The ELISA and hemagglutination assay had negative predictive values for Gram-negative bacteremia of 100 percent and 96 percent, respectively. CONCLUSION Elevation of cross-linked fibrin degradation products consistent with increased fibrinolytic activity occurs in all patients with Gram-negative bacteremia. Accordingly, the lack of elevation may be clinically useful in identifying patients less likely to have Gram-negative bacteremia.