Recently, soluble fibrin (SF) has been suggested as a more sensitive and specific marker for MI. Current assays detect a heterogeneous population of fibrin fragments and the relationship of SF to other markers of procoagulant and fibrinolytic activity is unknown. In this study, two novel immunoassays were used to characterize the relationship of SF to cross-linked fibrin fragments (XL-FDP) in MI. Concentrations of SF and fibrinopeptide A (FPA), a measure of fibrin 1 formation, were also correlated. SF was measured by ELISA with a monoclonal antibody (MAb) to a neoepitope formed after FPA is cleaved (Ortho Diagnostics). The XL-FDP were measured with a MAb specific for D-dimer (3B6) and with a fibrin-specific tag (ID2) (D-Dimer Gold, Agen). Concentrations of XL-FDP and SF were elevated at presentation in the blood of MI pts (n=93) (234.5±40.4 ng/ml, 32.4+5.3 |ag/ml) compared with samples from controls (n=29) (22.6±2.9 ng/ml, 1.7±0.26 ng/ml) (p<0.0001, p<0.0001). Complications of MI (defined as death, CHF, mural thrombus, or ventricular arrhythmia) were more common in patients who presented >10 hrs after the onset of ischémie symptoms (73% of patients presented >10 hrs) (p=0.01). Increases in SF, FPA, and XL-FDP concentrations were documented in 55.9%, 45.2%, and 73.9% of MI patients, but there was no relationship found between concentrations of these markers. On admission, concentrations of XL-FDP (p=0.003), but not SF (p=0.2), were related to the occurrence of Mi-related complications. Increases in SF and XL-FDP are frequent, but not diagnostic, in patients with MI, but XL-FDP appears to be a clinically useful marker of complications.