Activation of the contact system and inflammation after thrombolytic therapy in patients with acute myocardial infarction.
Thrombolytic therapy activates the contact system, and factor XII activation may activate the coagulation cascade and inflammation. It is not known whether an early inflammatory response is induced by thrombolytic therapy in patients with acute myocardial infarction (AMI). We prospectively measured the plasma levels of activated factor XII, cleaved kininogen, prothrombin fragment 1 + 2 (as indexes of the contact phase and coagulation activation), and interleukin-6 and C-reactive protein (CRP) (as indexes of inflammation) in 39 patients hospitalized for AMI within 12 hours of symptom onset: 26 receiving thrombolytic therapy and 13 heparin alone. Blood samples were collected at baseline and after 90 minutes and 24 hours. Patients undergoing thrombolysis had a significant early increase in activated factor XII (from 2.2 ng/ml at baseline to 4.7 ng/ml after 90 minutes; p = 0.0001), cleaved kininogen (from 26% to 37%; p = 0.001), and fragment 1 + 2 (from 1.4 to 2.1 nmol/L; p = 0.0001), whereas the 24-hour levels were similar to baseline levels. The levels of interleukin-6 significantly increased during the first 90 minutes (from 3.9 to 6.3 microg/ml; p = 0.001), and were even higher after 24 hours (11.9 ng/ml, p = 0.0001). CRP levels increased only after 24 hours (p = 0.0001). There were no changes in these parameters in patients receiving heparin alone, except for a 24-hour increase in interleukin-6 and CRP levels. Thus, in patients with AMI receiving thrombolytic therapy, early activation of inflammation parallels the activation of the contact system and the coagulation cascade, which might contribute to microvascular obstruction and reperfusion injury.
Merlini
Piera Angelica
PA
IV Division of Cardiology, Ospedale Niguarda, Milan, Italy. ardis001@planet.it
Cugno
Massimo
M
Rossi
Marco L
ML
Agricola
Pietro
P
Repetto
Alessandra
A
Fetiveau
Raffaella
R
Diotallevi
Paolo
P
Canosi
Umberto
U
Mannucci
Pier Mannuccio
PM
Ardissino
Diego
D
D002097:C-Reactive Protein / Q000378:metabolism*; D015956:Factor XIIa / Q000378:metabolism*; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D019679:Kininogen, High-Molecular-Weight / Q000097:blood*; D009203:Myocardial Infarction / Q000097:blood* / Q000188:drug therapy; D009205:Myocarditis / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood*; D015539:Platelet Activation / Q000502:physiology; D011516:Prothrombin; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use
D005343:Fibrinolytic Agents; D015850:Interleukin-6; D019679:Kininogen, High-Molecular-Weight; D010446:Peptide Fragments; C045879:prothrombin fragment 1.2; D011516:Prothrombin; D006493:Heparin; D002097:C-Reactive Protein; D015956:Factor XIIa; D010959:Tissue Plasminogen Activator