No activation of the common pathway of the coagulation cascade after a highly purified factor IX concentrate.
Purer factor IX concentrates, containing very little or no factor II or X, have been developed in an attempt to avoid the thromboembolic complications that occur with prothrombin complex concentrates (PCC), which also contain factors II and X and variable amounts of factor VII. To evaluate ex vivo the thrombogenic potential of one of these purer concentrates, we studied whether large single doses produced signs of activation of the coagulation cascade in patients with haemophilia B, and compared the results with those obtained after infusion of a PCC. Seven patients were infused with 50 IU/kg of factor IX concentrate and seven additional patients were subsequently infused with 100 IU/kg of the same concentrate. After the infusions, factor IX levels rose in proportion to the administered dose while the concentrations of factor II and factor X did not rise at all. At both doses of concentrate, we did not observe significant post-infusion increments in the levels of the factor X activation peptide (a measure of the activity of the factor VIIa-tissue factor complex and/or the factor IXa-VIIIa-activated surface complex), prothrombin fragment 1 + 2 (a measure of factor Xa activity), and fibrinopeptide A (a measure of thrombin activity). We also infused 10 patients with a PCC (50 IU/kg). After the infusions, significant rises in the concentrations of the factor X activation peptide and prothrombin fragment were observed. Therefore, it appears that the infusion of a PCC to patients with haemophilia B can augment factor X activation and subsequently thrombin generation in vivo and that this process can be abrogated by the administration of more pure factor IX concentrate.
Mannucci
P M
PM
Bianchi Bonomi Hemophilia and Thrombosis Center, University of Milan, Italy.
Bauer
K A
KA
Gringeri
A
A
Barzegar
S
S
Santagostino
E
E
Tradati
F C
FC
Rosenberg
R D
RD
D000293:Adolescent; D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects*; D001779:Blood Coagulation Factors / Q000494:pharmacology; D005164:Factor IX / Q000032:analysis / Q000302:isolation & purification / Q000494:pharmacology*; D005167:Factor VII / Q000032:analysis; D005170:Factor X / Q000032:analysis; D015951:Factor Xa / Q000032:analysis; D005344:Fibrinopeptide A / Q000032:analysis; D002836:Hemophilia B / Q000097:blood*; D006801:Humans; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis; D011516:Prothrombin / Q000032:analysis; D013997:Time Factors
D001779:Blood Coagulation Factors; D010446:Peptide Fragments; C045879:prothrombin fragment 1.2; D005344:Fibrinopeptide A; C025667:prothrombin complex concentrates; D005167:Factor VII; D011516:Prothrombin; D005164:Factor IX; D005170:Factor X; D015951:Factor Xa