F K Keating1, D A Whitaker, B E Sobel, D J Schneider. 1. Cardiology Unit, Department of Medicine, Fletcher Allen Health Care, McClure 1, University of Vermont, 111 Colchester Avenue, Burlington, VT 05401, USA. friederike.keating@vtmednet.org
Abstract
BACKGROUND: Patients with diabetes mellitus and acute coronary syndromes (ACS) derive enhanced benefit from treatment with glycoprotein (GP) IIb-IIIa inhibitors. To determine mechanisms potentially responsible we characterized the binding of fibrinogen to platelets from patients with and without diabetes in the presence and absence of GP IIb-IIIa antagonists. METHODS: GP IIb-IIIa antagonists (tirofiban, eptifibatide, and abciximab) were added in vitro to blood from patients with and without diabetes. Binding of fibrinogen to activated GP IIb-IIIa was assessed with the use of flow cytometry. The kinetics of binding of I(125)-abciximab and I(125)-fibrinogen to washed platelets from subjects with and without diabetes mellitus were determined. Glycation of platelet membrane proteins was measured with the fructosamine assay. RESULTS: In the presence of GP IIb-IIIa antagonists, activation-induced binding of fibrinogen to platelets was reduced to a greater extent (p<0.02) in blood from patients with diabetes. The greater inhibition in blood from patients with diabetes was seen with pharmacologic concentrations of tirofiban (50 ng/ml, by 27%), eptifibatide (1.5 microg/ml, by 24%), and abciximab (2 mg/ml, by 12%). Whereas the binding of I(125)-abciximab was similar to platelets from patients with diabetes and those without, the rate of binding of I(125)-fibrinogen was decreased with platelets from patients with diabetes. Binding after 5 min was reduced by 46% in those with diabetes (p<0.05). Platelet membrane proteins from patients with diabetes were glycated to a greater extent compared with those without diabetes. CONCLUSION: GP IIb-IIIa antagonists inhibit platelet activation to a greater extent in blood from patients with diabetes. The decreased rate of binding of fibrinogen early after activation of platelets appears to be a consequence of glycation and may promote inhibition by GP IIb-IIIa antagonists.
BACKGROUND:Patients with diabetes mellitus and acute coronary syndromes (ACS) derive enhanced benefit from treatment with glycoprotein (GP) IIb-IIIa inhibitors. To determine mechanisms potentially responsible we characterized the binding of fibrinogen to platelets from patients with and without diabetes in the presence and absence of GP IIb-IIIa antagonists. METHODS:GP IIb-IIIa antagonists (tirofiban, eptifibatide, and abciximab) were added in vitro to blood from patients with and without diabetes. Binding of fibrinogen to activated GP IIb-IIIa was assessed with the use of flow cytometry. The kinetics of binding of I(125)-abciximab and I(125)-fibrinogen to washed platelets from subjects with and without diabetes mellitus were determined. Glycation of platelet membrane proteins was measured with the fructosamine assay. RESULTS: In the presence of GP IIb-IIIa antagonists, activation-induced binding of fibrinogen to platelets was reduced to a greater extent (p<0.02) in blood from patients with diabetes. The greater inhibition in blood from patients with diabetes was seen with pharmacologic concentrations of tirofiban (50 ng/ml, by 27%), eptifibatide (1.5 microg/ml, by 24%), and abciximab (2 mg/ml, by 12%). Whereas the binding of I(125)-abciximab was similar to platelets from patients with diabetes and those without, the rate of binding of I(125)-fibrinogen was decreased with platelets from patients with diabetes. Binding after 5 min was reduced by 46% in those with diabetes (p<0.05). Platelet membrane proteins from patients with diabetes were glycated to a greater extent compared with those without diabetes. CONCLUSION:GP IIb-IIIa antagonists inhibit platelet activation to a greater extent in blood from patients with diabetes. The decreased rate of binding of fibrinogen early after activation of platelets appears to be a consequence of glycation and may promote inhibition by GP IIb-IIIa antagonists.
Authors: Anna Michno; Katarzyna Grużewska; Hanna Bielarczyk; Marlena Zyśk; Andrzej Szutowicz Journal: Pharmacol Rep Date: 2020-01-10 Impact factor: 3.024