The classic contact activation coagulation system emerges as a potentially important mechanism in arterial thrombosis. Recent studies not only indicate that coagulation factor (F) XII is associated with atherothrombotic coronary disease, but also that it contributes to clot formation via activation of downstream FXI. The time course of contact activation after an acute myocardial infarction (AMI), has not been studied. In addition, its relevance for arterial thrombosis has not been addressed in prospective studies. We measured the plasma concentrations of activated FXII (FXIIa), FXIa and Kallikrein in complex with their natural inhibitors in 135 consecutive patients with a documented first AMI (chest pain between 30 minutes and 24 hours accompanied by ST-segment elevation on ECG and/or elevated plasma levels of creatine kinase and troponin T). FXIIa-C1 inhibitor, kallikrein-C1 inhibitor, FXIa-C1 inhibitor and FXIa-antitrypsin complexes were measured in established homemade ELISAs (

Govers-Riemslag et al.
J Thromb Haemost
2007
;
5
:
1896
–1903
). Mean FXIIa-C1 inhibitor complexes were highest on admission (0.081 U/mL) as compared to day 4 (0.065 U/ml), when most patients were still hospitalized and treated with low molecular weight heparin (LMWH) and dual platelet inhibition (aspirin and clopidogrel). At 90 and 180 days after admission mean FXIIa-C1 inhibitor values were 0.064 U/mL, (P<0.05 vs. admission) and 0.067 U/mL, respectively. Except for 1 patient, kallikrein-C1 inhibitor complexes were undetectable at all time points. Mean FXIa-complexes were highest on day 4, in both the FXIa-C1 inhibitor assay (0.64 U/mL) and the FXIa-antitrypsin assay (0.33 U/mL, P<0.01 vs. admission). Mean FXIa-C1 inhibitor complexes decreased to 0.46 and 0.44 U/mL after 90 and 180 days (both P<0.05 vs. day 4), while FXIa-antitrypsin complexes decreased to 0.29 U/mL after 90 and 180 days (both P<0.0001 vs. day 4). Surprisingly, patients with one or more recurrent events (n=15; combined endpoint of death, recurrent MI, stroke, angiographic or percutaneous intervention) during follow-up of 180 days had lower FXIa-C1 inhibitor complexes on admission than those without such events (mean values 0.24 U/mL versus 0.67 U/mL in patients without events; P<0.05). These results indicate that the contact activation coagulation system is activated in atherothrombotic coronary disease. The degree of activation (reflected in FXIa-C1 inhibitor complexes) is inversely related to outcome, which may prognostically indicate that patients with evidence of intrinsic hypercoagulability on admission respond better to subsequent treatment (dual platelet inhibitors plus LMWH) than patients with less pronounced coagulation activity.

Topics:
coronary heart disease, st segment elevation, clotting cascade, complex, kininogenase, low-molecular-weight heparin, arterial thrombosis, angiogram, aspirin, blood coagulation factors

Author notes

Disclosure:Research Funding: The study was supported by grants from the Profileringsfonds of the Academic Hospital Maastricht and by an unrestricted grant from Pfizer.

2007, The American Society of Hematology
2007
Sign in via your Institution