THE IMPORTANCE OF ANTIBODY SPECIFICITY IN MEASURING CROSS-LINKED FIBRIN DEGRADATION PRODUCTS BY ELISA

We and others have previously shown that plasma concentrations of XL-F DPs are accurately characterized with an enzyme-linked immunosorbent a ssay (ELISA) based on the monoclonal antibody DD-3B6/22, which is spec ific for D-dimer, and a pan-specific tag antibody (DD-4D2/182) in pati ents with thrombotic disorders. However, in patients treated with fibr inolytic agents, increases in non-cross-linked fibrin(ogen) degradatio n products are detected by the pan-specific tag antibody due to format ion of complexes between non-cross-linked derivatives and XL-FDPs. Ass ays based on the use of fibrin degradation product-specific tag antibo dies appear to be more specific, but whether they would be clinically more informative is unclear. Accordingly, in the current study we meas ured concentrations of XL-FDPs with two ELISAs; one based on the pan-s pecific tag antibody (DD-4D2/182) and another based on a fibrin degrad ation product-specific tag antibody (DD-1D2/48) in patients treated wi th three well-characterized thrombolytic regimens: one associated with minimal fibrinogenolysis (100 mg tissue-type plasminogen activator [t -PA]) over 3 h), moderate fibrinogenolysis (100 mg t-PA over 90 min), and one with marked fibrinogenolysis (1.5 MU streptokinase [SK]). In p atients treated with t-PA, increases in XL-FDPs were closely correlate d with fibrinogenolysis, as characterized by increases in the concentr ation of the B beta 1-42 peptide, when measured with the pan-specific tag ELISA (r = 0.7), but not when measured with the fibrin degradation product-specific tag assay (r = 0.2). In patients treated with SK, co ncentrations of XL-FDPs were significantly higher (>2000 ng/ml) with t he pan-specific tag ELISA compared with the fibrin degradation product -specific tag ELISA (< 1000 ng/ml) 1, 2 and 8 h after start of the inf usion (P < 0.01). Concentrations of XL-FDPs were also higher in patien ts treated with SK compared with t-PA when measured with the pan-speci fic tag ELISA, but lower with SK with the fibrin-specific ELISA (P < 0 .01). The value of measurement of XL-FDPs in patients treated with fib rinolytic agents will need to be reappraised with the use of fibrin de gradation product-specific assays, which appear to provide more accura te information on the kinetics of cross-linked fibrin lysis in patient s treated with t-PA or SK.