The role of soluble cross-linked fibrin in D dimer immunoreactivity of plasmic digests

Abstract

Monoclonal antibody DD/3B6 reacts with a site near the gamma gamma isopeptide cross link and has been used to detect cross-linked fibrin degradation products in plasma as a marker for clot lysis. However, interpretation of the results is potentially complicated, because soluble cross-linked fibrin polymers contain a gamma gamma cross-link and may also react with the antibody before or after plasmic degradation. We have prepared plasmic digests of fibrinogen, soluble cross-linked fibrin polymers, and cross-linked particulate fibrin clot, have characterized their composition by electrophoresis, and have compared their D dimer immunoreactivities. Undegraded soluble cross-linked fibrin polymer showed no reactivity below 20 micrograms/ml, indicating that the epitope recognized by DD/3B6 is poorly reactive before plasmic degradation. The D dimer immunoreactivity of plasmic digests of particulate or of soluble cross-linked fibrin increased with progressive degradation, with stage 3 digests having 20-fold to 40-fold higher immunoreactivity than stage 1 digests. A stage 3 digest of fully cross-linked particulate fibrin reacted fourfold and 10-fold more than stage 3 digests of soluble fibrin polymers and untreated fibrinogen, which contained 21% and 8.5% soluble fibrin, respectively. Thus, D dimer immunoreactivity in stage 3 digests correlated with the amount of soluble cross-linked fibrin polymer in the undegraded starting material. These findings demonstrate that degradation of soluble or particulate cross-linked fibrin increases D dimer immunoreactivity progressively, with maximal reaction attained with stage 3 digests.(ABSTRACT TRUNCATED AT 250 WORDS)