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Prepublished online as a Blood First Edition Paper on July 3, 2003; DOI 10.1182/blood-2002-03-0954.
Submitted March 27, 2002
Accepted May 20, 2003
Coagulation activation and long-term outcome in acute coronary syndromes
Diego Ardissino*, Piera A Merlini, Pier M Mannucci, Kenneth A Bauer, Marcello Galvani, Filippo Ottani, Franca Franchi, Federico Bertocchi, and Robert D Rosenberg
Division of Cardiology, Ospedale Maggiore di Parma, Parma, Italy
Division of Cardiology, Ospedale Niguarda, Milan, Italy
Division of Cardiology, Ospedale GB Morgagni, Forli, Italy
Department of Medicine, VA Healthcare System, Boston, MA, USA
Department of Biology, Massachusetts Institute of Technology, Boston, MA, USA
Department of Medicine, Policlinico di Milano, Milan, Italy
Department of Cardiology, Ospedaledi Ravenna, Ravenna, Italy
* Corresponding author; email: ardis001{at}planet.it.
Rationale: After an episode of unstable angina or myocardial infarction, a high proportion of patients show biochemical signs of coagulation activation, expressed as persistently elevated thrombin generation, in their blood. It is not known whether this has any influence on long-term outcome. Objective: In this prospective multicenter cohort study we assessed the relation of persistently elevated thrombin generation to outcome in patients with acute coronary syndromes. A total of 319 consecutive patients with acute coronary syndromes enrolled in GUSTO IIb trial. Plasma prothrombin fragment 1+2 levels, an index of "in vivo" thrombin generation, was measured during the acute phase and after one, six and 12 months, and its relation to outcome was assessed during a median 29-month follow-up. Findings: The primary end-point of cardiac death or myocardial (re)infarction occurred in 61 patients (19%). There was a U-shaped relation between plasma prothrombin fragment 1+2 levels and the risk of developing the primary end-point: intermediate levels (1.5-1.9 nmol/L) were associated with the lowest risk, whereas both higher (> 1.9 nmol/L) and lower (<1.5 nmol/L) values were associated with an increased risk (RR 1.56, 95% confidence interval 1.25-2.28; RR 1.35; 95% confidence interval 1.11-1.86; respectively) Conclusions: After an episode of acute coronary syndrome, both high and low levels of thrombin generation are predictors of an increased risk of an unfavourable outcome.
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