Factor Xa and prothrombin: mechanism of action of FEIBA.
A complex consisting of activated factor X (FX) (enzyme) and prothrombin (substrate), both highly purified from human plasma and virus inactivated, was formulated, characterised biochemically as well as in animal studies, and given the name Partial Prothrombinase (PPT). In vitro, PPT shortened the clotting time of a high-titre human factor VIII (FVIII) inhibitor plasma in a manner similar to that of the activated prothrombin complex concentrate FEIBA and triggered coagulation in plasma samples in which factor V (FV) is present. In vivo, the ability of PPT to activate coagulation in both chimpanzees and baboons was equivalent to that of FEIBA. PPT also triggered coagulation in a von Willebrand factor(vWF)-deficient dog and controlled bleeding in rabbits with antibody-induced haemophilia A. Thus, studying the mechanism of action of PPT also explains the therapeutic principle of FEIBA.
Turecek
P L
PL
Baxter Hyland Immuno, Vienna, Austria.
Varadi
K
K
Gritsch
H
H
Auer
W
W
Pichler
L
L
Eder
G
G
Schwarz
H P
HP
D000818:Animals; D000906:Antibodies; D001777:Blood Coagulation / Q000187:drug effects; D001779:Blood Coagulation Factors / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology; D004195:Disease Models, Animal; D004285:Dogs; D005169:Factor VIII / Q000276:immunology; D015951:Factor Xa / Q000494:pharmacology*; D005260:Female; D006467:Hemophilia A / Q000139:chemically induced / Q000188:drug therapy; D006470:Hemorrhage; D006801:Humans; D008297:Male; D002679:Pan troglodytes; D010215:Papio; D011516:Prothrombin / Q000032:analysis / Q000494:pharmacology*; D011817:Rabbits; D013917:Thrombin / Q000096:biosynthesis / Q000187:drug effects; D013997:Time Factors; D014842:von Willebrand Diseases / Q000188:drug therapy
D000906:Antibodies; D001779:Blood Coagulation Factors; D011516:Prothrombin; D005169:Factor VIII; C065655:anti-inhibitor coagulant complex; D013917:Thrombin; D015951:Factor Xa