Thrombin activity throughout the acute phase of acute ST-elevation myocardial infarction and the relation to outcome.
BACKGROUND
Thrombin and plasmin play a central role in ongoing thrombosis and platelet activation in patients with acute ST-elevation myocardial infarction (STEMI). Data of thrombin and plasmin activity in the early course of STEMI and the relation to outcome are scarce.


METHODS
We included 68 consecutive patients (53 male, 59 +/- 11.4 years) with STEMI who underwent acute catheter-based reperfusion therapy within the first 12 h after onset of symptoms. Blood samples were taken at admission and after 4, 8, 12 and 24 h. Thrombin activity and generation was measured by changes in the thrombin/antithrombin-III complex (TAT) and prothrombin fragment (F1.2); plasmin was measured by changes in the plasmin-alpha(2)/antiplasmin complex (PAP). A follow-up with respect to the combined primary endpoint consisting of death, acute myocardial infarction or urgent need for revascularization up to 6 weeks post-discharge was carried out.


RESULTS
TAT values showed no significant change over time in patients with and without the primary endpoint but there was a borderline difference between these groups at 4 h after admission (event group 9.0 vs no event group 4.7 microg l(-1), p = 0.057). F1.2 values were different between groups only after 24 h (event group 1.5 vs no event group 0.9 nmol l(-1), p = 0.028) and did not differ in serial sampling of 24 h. PAP values were higher in patients with events after 4 and 8 h and declined over time in the group without events (p <0.001). Odds ratios (OR) with respect to the primary endpoint were highest for TAT >4.8 microg l(-1) at 0 h and TAT >8.4 microg l(-1) at 4 h (OR 7.1, 95% confidence interval (CI) 1.5-34, p = 0.015 and OR 5.5, 95% CI 1.5-20.0, p = 0.01, respectively). The predictive value of plasmin concentrations were equally high after 4 h (PAP >962 microg l(-1); OR 6.8, 95% CI 1.8-26.2, p = 0.005) and 8 h (PAP >495 microg l(-1), OR 6.7, 95% CI 1.4-32.9, p = 0.024). Values for F1.2 were only predictive after 24 h (F1.2 >0.85 nmol l(-1), OR 13, 95% CI 1.4-117.8, p = 0.023).


CONCLUSIONS
Markers of thrombin and plasmin activity in acute STEMI are related to outcome. The marker for thrombin generation F1.2 becomes a significant predictor of outcome at 24 h after admission, reflecting the potentially adverse effects of ongoing thrombin generation. This underlines the potential for direct thrombin inhibition and individualization of treatment by thrombin markers in STEMI.
Ulrich-Möckel
Natalie-Viviane
NV
Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
Riehle
Matthias
M
Vollert
Jörn
J
Heller
Günther
G
Störk
Thomas
T
Riess
Hanno
H
Müller
Christian
C
Frei
Ulrich
U
Möckel
Martin
M
D015415:Biomarkers / Q000097:blood; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000201:enzymology* / Q000601:surgery; D013917:Thrombin / Q000378:metabolism*; D016896:Treatment Outcome
D015415:Biomarkers; D013917:Thrombin; D005341:Fibrinolysin