Blockade of GPIIb/IIIa by eptifibatide and tirofiban does not alter tissue factor induced thrombin generation in human endotoxemia.
Activated platelets facilitate thrombin generation by providing a catalytic surface on which coagulation activation occurs. The glycoprotein (GP) IIb/IIIa receptor might play a major role in this process as shown by in vitro and animal experiments. However, it is controversial whether the GPIIb/IIIa receptor facilitates tissue factor-induced thrombin generation in humans as well. We therefore investigated whether two clinically used GPIIb/IIIa antagonists (tirofiban and eptifibatide) may blunt TF-induced coagulation in humans. Thirty male volunteers received 2 ng/kg endotoxin and standard doses of eptifibatide, tirofiban or placebo over 5 hours in a randomized, double-blind, placebo-controlled, double-dummy parallel-group trial. Markers of thrombin generation (prothrombin fragment 1+2, thrombin-antithrombin complexes), fibrinolysis (D-dimer, plasmin-antiplasmin complexes) as well as inflammatory markers (interleukin-6, tumor necrosis factor-alpha) were measured by enzyme linked immunoasssays, TF-mRNA expression was quantified by RT-PCR. Neither eptifibatide nor tirofiban influenced LPS-induced coagulation activation or fibrinolytic activity. Additionally, the increase of TNF-alpha and IL-6 was similar in all groups. In conclusion, GPIIb/IIIa blockade with eptifibatide or tirofiban did not influence TF-induced coagulation activation in human low grade endotoxemia.
Derhaschnig
Ulla
U
Department of Clinical Pharmacology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
Pachinger
Christine
C
Schweeger-Exeli
Ingrid
I
Marsik
Claudia
C
Jilma
Bernd
B
D000328:Adult; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects; D004311:Double-Blind Method; D019446:Endotoxemia / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D000077542:Eptifibatide; D006801:Humans; D008297:Male; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000032:analysis; D013917:Thrombin / Q000096:biosynthesis*; D013925:Thromboplastin / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D000077466:Tirofiban; D014443:Tyrosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*
D015415:Biomarkers; D010455:Peptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D012333:RNA, Messenger; D014443:Tyrosine; D013925:Thromboplastin; D013917:Thrombin; D000077466:Tirofiban; D000077542:Eptifibatide