Benefical effects of reteplase in combination with abciximab: platelet/leukocyte interactions and coagulation system.
Pathophysiological aspects of acute myocardial infarction include altered hemostatic and fibrinolytic systems as well as platelet activation. Treatment with thrombolytics and GP IIb/IIIa antagonists has been described as having an additional influence on these systems. We investigated the effects of a new thrombolytic regimen with half-dose double-bolus reteplase (2 x 5 IU, 20 patients) combined with abciximab versus full dose reteplase (2 x 10 IU, 18 patients) on platelet-granulocyte complexes and on thrombin-antithrombin III complexes in patients with acute ST-segment elevation myocardial infarction. In vivo, the thrombolytic regimen with half-dose reteplase in combination with abciximab caused fewer platelet-granulocyte aggregates (measured as percentage of CD41-positive granulocytes) and a lower paradoxical activation of the coagulation system (measured as thrombin-antithrombin III complex) compared with the reteplase regimen. The combination regimen could therefore have benefical effects on platelet-induced leukocyte activation and leukocyte-mediated proinflammatory/cytotoxic effects as well as on granulocyte-induced effects on endothelium, tissue damage and coagulation. This could be, at least in part, a possible explanation for the significantly lower rates of reinfarction, recurrent ischaemia and percutaneous coronary interventions observed during the early phase after an acute myocardial infarction in the combination group in the GUSTO-V trial.
Szabo
S
S
Städtisches Klinikum, Department of Internal Medicine II, Solingen, Germany. KrisztinaSzb@aol.com
Walter
T
T
Etzel
D
D
Ehlers
R
R
Kazmaier
S
S
Beyer
M E
ME
Hoffmeister
H M
HM
D000077284:Abciximab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000990:Antithrombin III / Q000037:antagonists & inhibitors; D001792:Blood Platelets / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D009203:Myocardial Infarction / Q000188:drug therapy*; D010447:Peptide Hydrolases; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D005343:Fibrinolytic Agents; D007140:Immunoglobulin Fab Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; C046193:antithrombin III-protease complex; D000990:Antithrombin III; C087896:reteplase; D010447:Peptide Hydrolases; D010959:Tissue Plasminogen Activator; D000077284:Abciximab