BACKGROUND: In patients with acute myocardial infarction (AMI), activated platelets and altered haemostatic/fibrinolytic systems with and without thrombolytic therapy are known. Platelets thereby interact with neutrophils, stimulated endothelial cells and with monocytes leading to adverse effects on further myocardial damage. Thrombolysis in these patients is still hampered by procoagulant effects favoring early reocclusion. The additional treatment with a GPIIb/IIIa antagonist aimed to minimize early reocclusion thus improving the present therapeutic regimen. METHODS: In 38 patients with AMI, we investigated the effects of a thrombolytic regimen with half reteplase (r-PA) dose plus abciximab vs. full dose r-PA on membrane-bound adhesion molecules (CD41, CD42b, CD40, CD40L) expressed on platelets, neutrophils and monocytes as well as on soluble platelet-selectin as interaction and activation markers of these cells. RESULTS: The combination group had significantly (p < 0.05) lower sP-selectin levels over 48 h vs. the group treated with full dose r-PA. After 3 h, the percentage of CD41 and CD42b positive monocytes and granulocytes as well as the percentage of CD40 positive granulocytes and the percentage of CD40Lpositive monocytes markedly (p < 0.01, p < 0.05) decreased in the combination group vs. data at admission compared with the r-PA group indicating less leukocyte-patelet adhesion. CONCLUSIONS: The thrombolytic regimen with half dose r-PA and abciximab had a benefical influence on platelet activation and induced a more marked decrease of platelet-monocyte, and in part, platelet-granulocyte aggregates compared with the r-PA regimen. This could contribute to a probably lesser monocyte activation state with favourable effects on monocyte-endothelial adhesion and a consecutively possible influence of myocardial damage, a reduction of the additionally acute local inflammatory processes and a reduction of adherence of platelet-granulocyte aggregates to subendothelium.
RCT Entities:
BACKGROUND: In patients with acute myocardial infarction (AMI), activated platelets and altered haemostatic/fibrinolytic systems with and without thrombolytic therapy are known. Platelets thereby interact with neutrophils, stimulated endothelial cells and with monocytes leading to adverse effects on further myocardial damage. Thrombolysis in these patients is still hampered by procoagulant effects favoring early reocclusion. The additional treatment with a GPIIb/IIIa antagonist aimed to minimize early reocclusion thus improving the present therapeutic regimen. METHODS: In 38 patients with AMI, we investigated the effects of a thrombolytic regimen with half reteplase (r-PA) dose plus abciximab vs. full dose r-PA on membrane-bound adhesion molecules (CD41, CD42b, CD40, CD40L) expressed on platelets, neutrophils and monocytes as well as on soluble platelet-selectin as interaction and activation markers of these cells. RESULTS: The combination group had significantly (p < 0.05) lower sP-selectin levels over 48 h vs. the group treated with full dose r-PA. After 3 h, the percentage of CD41 and CD42b positive monocytes and granulocytes as well as the percentage of CD40 positive granulocytes and the percentage of CD40L positive monocytes markedly (p < 0.01, p < 0.05) decreased in the combination group vs. data at admission compared with the r-PA group indicating less leukocyte-patelet adhesion. CONCLUSIONS: The thrombolytic regimen with half dose r-PA and abciximab had a benefical influence on platelet activation and induced a more marked decrease of platelet-monocyte, and in part, platelet-granulocyte aggregates compared with the r-PA regimen. This could contribute to a probably lesser monocyte activation state with favourable effects on monocyte-endothelial adhesion and a consecutively possible influence of myocardial damage, a reduction of the additionally acute local inflammatory processes and a reduction of adherence of platelet-granulocyte aggregates to subendothelium.
Authors: F Mach; U Schönbeck; G K Sukhova; T Bourcier; J Y Bonnefoy; J S Pober; P Libby Journal: Proc Natl Acad Sci U S A Date: 1997-03-04 Impact factor: 11.205
Authors: Sebastian Szabo; Ronald Letsch; Raila Ehlers; Thomas Walter; Silke Kazmaier; Uwe Helber; Hans Martin Hoffmeister Journal: Thromb Res Date: 2002-04-15 Impact factor: 3.944