Reactivity of soluble fibrin assays with plasmic degradation products of fibrin and in patients receiving fibrinolytic therapy

The ability to identify the products of thrombin and plasmin action on fibr inogen is important in patients with thrombotic and fibrinolytic disorders. New assays have been developed for "soluble fibrin" which represents solub le derivatives other than fibrinopeptides formed from fibrinogen by thrombi n. These assays are either immunological using antibodies for fibrin-specif ic neoepitopes, or functional and based on the cofactor activity of soluble fibrin in the tissue plasminogen activator (t-PA)-mediated conversion of p lasminogen to plasmin. As plasmic derivations of fibrin share structural fe atures with soluble fibrin, they may be reactive with assays for soluble fi brin. Therefore, we prepared plasmic digests of fibrin and determined the d egree of reactivity with four soluble fibrin assays. Three assays used Mabs directed toward the fibrin-specific neoepitopes at alpha 17-23 (A), gamma 312-324 (B) and alpha 17-78 (D). A fourth (C) was based on t-PA co-factor a ctivity. Tests A and C demonstrated marked crossreactivity with fibrin degr adation products, and digests containing the largest derivatives showed gre atest reactivity. Plasmic derivatives of crosslinked fibrin had greater rea ctivity than those of non-crosslinked fibrin. Tests B and D demonstrated mi nimal reactivity with plasmic derivatives of crosslinked or of non-crosslin ked fibrin. Samples from patients with lower limb peripheral arterial occlu sion were assayed for soluble fibrin, D-dimer and fibrinogen at presentatio n and eight hours after thrombolytic therapy. Variable results were seen at presentation with elevations in 13, 1, 0 and 4 of 19 patients using Tests A, B, C and D, respectively. After fibrinolytic therapy, marked increases i n soluble fibrin levels were observed up to 600-fold above normal. A strong correlation between baseline levels was observed with Test B and Test D, w hich shelved the least cross-reactivity with plasmic derivations. After thr ombolytic therapy there were either weak or no correlations among the diffe rent assays. The results demonstrate that assays for soluble fibrin may rea ct with plasmic derivatives of fibrin and this must be considered in interp reting clinical results.