Pr. Eisenberg et al., THE IMPORTANCE OF ANTIBODY SPECIFICITY IN MEASURING CROSS-LINKED FIBRIN DEGRADATION PRODUCTS BY ELISA, Blood coagulation & fibrinolysis, 8(2), 1997, pp. 105-113
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.