QUANTITATION OF VENOUS CLOT LYSIS WITH THE D-DIMER IMMUNOASSAY DURING FIBRINOLYTIC THERAPY REQUIRES CORRECTION FOR SOLUBLE FIBRIN DEGRADATION

Plasma cross-linked fibrin-degradation products were analyzed using a D-dimer (DD) immunoassay in patients with deep vein thrombosis (DVT) or acute myocardial infarction (MI) treated with fibrinolytic therapy, and the results were correlated with clot lysis documented angiographically. In 13 patients with DVT, the mean DD concentration increased 10-fold (1,074±252 to 10,333±1,004 ng/ml) during therapy, but neither the peak level nor the DD concentration integrated over the course of therapy correlated with clot lysis. Since plasma DD can derive from degradation of soluble plasma fibrin as well as from thrombi, the contribution of the former was estimated by in vitro incubation of the pretreatment plasma with plasminogen activator. Subtraction of this value from the measured posttreatment DD concentration provided a "corrected" level that represented DD originating from lysis of thrombi. This modification resulted in improved correlation of DD levels with clot lysis. The mean corrected peak DD was higher in patients with successful thrombolysis (8,780±1,352 ng/ml) compared with patients without lysis (3,075±589 ng/ml, p<0.001). There was a moderate correlation between the volume of clot lysed and the corrected peak DD (r=0.62) and a higher correlation with the corrected DD integrated over the course of treatment (r=0.97). By contrast, the corrected DD concentrations were near zero in patients treated for MI with or without thrombolytic reperfusion, suggesting that fibrin in small coronary thrombi did not contribute significantly to total plasma DD during therapy. These findings indicate that the elevation in cross-linked fibrin-degradation products during fibrinolytic therapy results from degradation of soluble fibrin as well as from lysis of thrombi. Adjustment of plasma DD concentrations for the contribution from degradation of soluble fibrin offers an approach to noninvasive monitoring of venous clot lysis during fibrinolytic therapy.