Assessment of markers of thrombin generation in patients with acute myocardial infarction complicated by ventricular fibrillation.
BACKGROUND
In most cases, sudden cardiac death is triggered by ischemia-related ventricular tachyarrhythmias and accounts for 50% of deaths from cardiovascular disease in developed countries. Chronic elevation of indicators of coagulation activation has been found in patients with coronary heart disease, but a role of coagulation activation as a potential risk factor for ventricular fibrillation (VF) during acute myocardial infarction (MI) has not been investigated.


METHODS
We enrolled 50 patients with a history of MI, of whom 26 presented with VF in the acute phase of myocardial ischemia; 24 patients had an acute MI without ventricular tachyarrhythmias. Levels of thrombin-antithrombin complexes (TAT), prothrombin fragment F1 + 2 (F1 + 2), fibrinopeptide A (FPA), plasmin-antiplasmin complexes (PAP), protein C, antithrombin, activated partial thromboplastin time (aPTT), thromboplastin time, D-Dimer, fibrinogen, and high-sensitivity C-reactive protein (hs-CRP) were measured in plasma samples of all patients. Blood collection was obtained sequentially in two separate settings. Patients were studied at a median of 351 days after the acute coronary event.


RESULTS
Higher levels of TAT complexes (13.4 +/- 22.2 vs. 3.03 +/- 4.3 microg/l; p = 0.02), FPA (79.7 +/- 132.3 vs. 24.04 +/- 41.3 ng/ml; p = 0.04), and F1+2 (1.89 +/- 1.3 vs. 1.16 +/- 0.5 nmol/l; p = 0.01) were observed in patients with VF compared with patients without ventricular tachyarrhythmias during the acute phase of MI. D-Dimer levels displayed a trend without reaching statistical significance (0.69 +/- 0.48 vs. 0.48 +/- 0.24 mg/l; p = 0.06). No differences were found in hs-CRP (3.25 +/- 4.5 vs. 4.4 +/- 8.8 mg/l; p = 0.5) and fibrinogen (2.8 +/- 0.9 vs. 2.7 +/- 0.9 g/l; p = 0.6) measurements. Repeat assessment of markers of coagulation activation at a median of 847 days revealed a highly significant decrease in patients with VF.


CONCLUSIONS
Markers of thrombin generation are transiently increased in patients with VF during the acute phase of MI. These findings have implications for risk assessment and genetic screening of patients prone to VF during acute myocardial ischemia.
Elmas
Elif
E
Department of Cardiology, First Department of Medicine, University of Heidelberg, Mannheim, Germany. elif.elmas@med.ma.uni-heidelberg.de
Kaelsch
Thorsten
T
Wolpert
Christian
C
Sueselbeck
Tim
T
Bertsch
Thomas
T
Dempfle
Carl Erik
CE
Borggrefe
Martin
M
D000990:Antithrombin III; D000991:Antithrombins / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005344:Fibrinopeptide A / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000150:complications; D010446:Peptide Fragments / Q000097:blood; D010447:Peptide Hydrolases / Q000097:blood; D011486:Protein C / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism*; D013918:Thrombin Time; D014693:Ventricular Fibrillation / Q000097:blood* / Q000150:complications
D000991:Antithrombins; D015415:Biomarkers; D010446:Peptide Fragments; D011486:Protein C; C046193:antithrombin III-protease complex; D005344:Fibrinopeptide A; D000990:Antithrombin III; D011516:Prothrombin; D010447:Peptide Hydrolases; D013917:Thrombin