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Fibrin fragment D-dimer and fibrinogen B beta peptides in plasma as markers
of clot lysis during thrombolytic therapy in acute myocardial infarction
CM Lawler, EG Bovill, DC Stump, DJ Collen, KG Mann and RP Tracy
Department of Biochemistry, University of Vermont, College of Medicine,
Burlington 05405.
The validity of markers in plasma of in vitro thrombolysis was investigated
in 12 patients with extensive fibrinogen breakdown (greater than 80%, group
1) and in 12 patients with minimal breakdown (less than 20%, group 2). The
patients were treated with 100 mg of recombinant tissue-type plasminogen
activator (rt-PA) in the "Thrombolysis in Myocardial Infarction II" (TIMI
II) trial. Cross- linked fibrin degradation product levels were measured
with two variant enzyme-linked immunosorbent assays (ELISAs), both using a
fibrin fragment D-dimer specific capture antibody. In one instance, a tag
antibody was used that cross-reacts with fibrinogen (pan-specific tag
ELISA); in the other, the tag antibody was specific for fibrin fragment D
(fibrin-specific tag ELISA). Apparent concentrations of cross-linked fibrin
degradation products at baseline were within normal limits with both assays
in most patients. At 8 hours after rt-PA infusion, the measured
cross-linked fibrin degradation products were increased about twofold to
fourfold in group 2 with both assays. However, in group 1, levels were
significantly higher with the pan-specific tag ELISA (5.8 +/- 4.2
micrograms/mL) compared with the fibrin-specific tag ELISA (1.5 +/- 1.3
micrograms/mL). This observation was most likely a result of detection of
fibrinogen degradation products in the pan-specific ELISA. Apparent levels
of fibrinopeptide B beta 1-42, a marker of fragment X formation, increased
during thrombolysis from 4.2 +/- 2.8 pmol/mL to 2,000 +/- 230 pmol/mL in
group 1 and from 4.1 +/- 2.1 pmol/mL to 300 +/- 43 pmol/mL in group 2, and
were correlated significantly with the extent of fibrinogen breakdown (r =
-0.8). Fibrinopeptide beta 15-42 levels increased from 4.3 +/- 3 pmol/mL to
70 +/- 19 pmol/mL in group 1, but did not increase in group 2. The apparent
increase in group 1 could be explained by cross-reactivity of
fibrinopeptide B beta 1-42 in the fibrinopeptide beta 15-42 assay. We
conclude that cross-linked fibrin degradation product levels as measured
with a pan-specific tag ELISA and fibrinopeptide beta 15-42 levels as
measured with certain monoclonal antibody-based ELISA are influenced by the
extent of fibrinogen degradation. Fibrinopeptide B beta 1-42 is a marker
specific for fibrinogen breakdown. Cross-linked fibrin degradation product
levels, measured with a fibrin-specific tag ELISA, appear to be markers
specific for thrombolysis. Consequently, assays similar to the fibrin-
specific tag ELISA may provide more accurate information when correlated
with clinical endpoints.
Volume 76,
Issue 7,
pp. 1341-1348,
10/01/1990
Copyright © 1990 by The American Society of Hematology
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