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

Abstract

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.