FIBRIN DEGRADATION PRODUCT (FNDP) ASSAYS - ANALYSIS OF STANDARDIZATION ISSUES AND TARGET ANTIGENS IN PLASMA

The in vivo formation of fibrin and its subsequent secondary fibrinoly tic digestion yields a variety of crosslinked fibrin degradation produ cts (XL/FnDP), One of these is known as D-dimer and a variety of ELISA -type commercial kits using monoclonal antibodies to D-dimer have been developed. We have investigated the possibility of establishing a sta ndard such that these various kits might indicate the same levels of D -dimer in the same samples. We have concluded that because it seems th at each individual monoclonal antibody to D-dimer targets a unique and distinct epitope in the FnDP fraction the notion of introducing a sta ndard D-dimer which will respond uniformly to each D-dimer monoclonal antibody is not feasible. Using various monoclonal and polyclonal anti bodies in conjunction with gel exclusion chromatography we have examin ed human plasma derived from patients with disseminated intravascular coagulation (DIC) which contained high levels of fibrin degradation pr oducts (FnDP). The data suggested that the FnDP fraction in plasma con tained mostly high molecular weight (>2x10(6) daltons) crosslinked fra gments which contain high levels of fibrinopeptide A. Many of these cr osslinked fragments crossreact with antibodies to D-dimer because they each contain D-dimer as a structural component. On the basis of this data, a novel sequence of events is proposed which may occur during th e aggregation of fibrin in vivo.