Early risk stratification of unstable angina non-Q myocardial infarction: biochemical markers of coronary thrombosis

Coronary thrombosis is an important determinant of prognosis in patients wi th acute coronary syndromes (ACS), However, the identification of patients at high-risk for progression of coronary thrombosis is difficult partly bec ause we currently lack clinically meaningful laboratory methods for its det ection. The most promising approaches involve the measurement in plasma of markers of fibrin formation and degradation. Thrombin activity, as reflecte d by plasma or urine concentrations of fibrinopeptide A, is increased in pa tients with ACS and is associated with adverse outcome. However, the use of fibrinopeptide A as a marker of fibrin formation is limited by the very sh ort half-life of the compound, by artifact due to sample acquisition, and b y extremely long turnaround times. To overcome these limitations, measureme nt of soluble fibrin has been proposed. We have recently explored the progn ostic value of a new fibrin-specific ELISA assay for soluble fibrin in pati ents with ACS and found that patients with the highest levels had a 2-fold increased risk of early and late cardiac events. Increases in plasma concen trations of cross-linked fibrin degradation products (XL-FDPs), which refle ct increased fibrin turn-over, are a marker of risk for complications of my ocardial infarction. However, until recently, assays for XL-FDPs lacked spe cificity, because they did not distinguish between fibrin and fibrinogen de gradation products. Recently, fibrin-specific ELISAs have been described an d a rapid whole blood assay for D-dimer has been developed, We recently val idated the prognostic value of this whole blood agglutination assay in pati ents with ACS. These results suggest that: (1) The detection of significant activation of the coagulation and/or fibrinolytic system may be important for rapid risk stratification of patients with ACS; (2) patients with bioch emical evidence of ongoing coronary thrombosis may particularly benefit fro m aggressive antithrombotic strategies; (3) sequential measurement of these markers may be useful to guide antithrombotic treatment during the unstabl e phase of coronary artery disease. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.