Isolation of fibrinogen-fibrin related antigen from human plasma by immuno-affinity chromatography: its characterization in normal subjects and in defibrinating patients with abruptio placentae and disseminated cancer.

Abstract

Highly purified fibrinogen-fibrin related antigen (FR-antigen) was isolated with good recovery from 1.0--2.0 ml of human plasma, by immuno-affinity chromatography with antibody specific for fibrinogen and fibrin, and plasmin degradation products X, Y, D and D-D dimer. In FR-antigen from defibrinating patients there was evidence for thrombin activity alone (mainly disseminated cancer) or both plasmin and thrombin (mainly abruptio placentae). Thus, the molar ratio of N-terminal Gly-Tyr in the FR-antigen of 18 of 20 patients strongly suggested thrombin activity (95th percentile). In addition, sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) on unreduced samples frequently showed bands similar in mol wt to fragments X, Y and D, and in the reduced samples A alpha and B beta chain degradation, both indicating plasmin activity. 'N-terminal beta chain Ala' was elevated in the antigen of four of 20 patients, also suggesting plasmin activity (99th percentile). Combined thrombin, plasmin and factor-XIII activity, as shown with high levels of serum FR-antigen (greater than 10 mg/dl). In some defibrinating patients, especially those with disseminated cancer, heterogeneity of unreduced FR-antigen and A alpha chain degradation, both indicators of mild plasmin-like activity which are commonly seen in normals, were absent.