Aprotinin: is it prothrombotic?
Controversy continues as to whether aprotinin (Trasylol) is prothrombotic. The recent discovery of the thrombin receptor family, known as the protease-activated receptor family (PAR) has been essential in aiding our understanding of the mechanism of action of aprotinin. Our results show that aprotinin has no effect on platelet aggregation induced by adrenaline, adenosine diphosphate, phorbol-12-myristate-13-acetate, collagen or PAR 1 agonist peptide. However, aprotinin inhibits thrombin-induced platelet activation as assessed by macroaggregation, microaggregation and platelet membrane calcium flux. Aprotinin inhibits proteolytic activation of platelets, but platelets can still be activated by non-proteolytic mechanisms.
Poullis
M
M
National Heart and Lung Institute, Imperial College School of Medicine at Hammersmith, London, UK. mpoullis@hotmail.com
Landis
R C
RC
Taylor
K M
KM
D000244:Adenosine Diphosphate / Q000494:pharmacology; D007611:Aprotinin / Q000009:adverse effects* / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D006490:Hemostatics / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011480:Protease Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin / Q000737:chemistry / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D019851:Thrombophilia / Q000139:chemically induced*; D014357:Trypsin / Q000494:pharmacology
D006490:Hemostatics; D009842:Oligopeptides; D010446:Peptide Fragments; D011480:Protease Inhibitors; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin; C082835:thrombin receptor peptide (42-47); C083977:phenylalanyl-leucyl-leucyl-arginyl-asparagine; D000244:Adenosine Diphosphate; D003094:Collagen; D007611:Aprotinin; D014357:Trypsin; D013917:Thrombin; D019204:GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate; D004837:Epinephrine