rFVIIai in Acute Coronary Syndromes.
Following vessel wall injury, tissue factor (TF) is exposed and forms complexes with already activated factor VII (FVIIa) present in the circulating blood, thereby initiating the hemostatic process. After the first FXa is formed, the TF pathway inhibitor (TFPI) forms a complex with FXa, and a quaternary complex is formed, TF/FVIIa/ FXa/TFPI, which inhibits the first step of the hemostatic pathway. Recombinant activated FVII (rFVIIa) has been developed for use as a hemostatic agent (NovoNordisk A/S, Denmark). Active site-inactivated rFVIIa (rFVIIai) has also been prepared and was shown to have a faster association to and a slower dissociation from TF than rFVIIa, resulting in a lower calculated Kd of rFVIIai compared with rFVIIa. In various animal models rFVIIai has been demonstrated to prevent or diminish immediate thrombus formation at the site of vessel wall injury (athroplasty or other forms of mechanical injury) as well as the development of long-term intima thickening. The inflammatory response following endotoxin-induced sepsis was shown to decrease after administration of rFVIIai. Also, survival increased in the rFVIIai-treated animals in this study. In addition, ischemia-reperfusion injury was mitigated by rFVIIai. In a limited number of patients undergoing percutaneous transluminal coronary angioplasty (PTCA), rFVIIai was observed to allow PTCA to be performed at lower doses of heparin than what has been reported previously.
Sorensen
Brit Binow
BB
Haemostasis Biology, Novo Nordisk A/S, Maaløv, Denmark.
Hedner
Ulla
U
Erhardtsen
Elisabeth
E
D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D001158:Arteries / Q000293:injuries; D001777:Blood Coagulation / Q000502:physiology; D015942:Factor VIIa / Q000493:pharmacokinetics / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use*; D015951:Factor Xa / Q000502:physiology; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006490:Hemostatics / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008074:Lipoproteins / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000628:therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use*; D018805:Sepsis / Q000628:therapy; D013925:Thromboplastin / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology; D013927:Thrombosis / Q000209:etiology / Q000503:physiopathology
D000893:Anti-Inflammatory Agents; D005343:Fibrinolytic Agents; D006490:Hemostatics; D008074:Lipoproteins; D011994:Recombinant Proteins; C051928:lipoprotein-associated coagulation inhibitor; C427263:phenylalanyl-phenylalanyl-arginyl-recombinant FVIIa; D013925:Thromboplastin; D015942:Factor VIIa; D015951:Factor Xa