Impact of different inhibitor reactivities with commercial factor VIII concentrates on thrombin generation.
In order to describe the haemostatic role of a variation in inhibitor reactivity with different factor VIII (FVIII) concentrates, we have compared inhibitor titres against a panel of FVIII concentrates and correlated titre with the capacity to inhibit thrombin generation. Three plasma-derived concentrates were tested in vitro in mixing experiments with inhibitor plasmas from 11 patients with severe haemophilia A: Fanhdi, which contains von Willebrand factor (VWF) with a final ratio of approximately 1:1 (VWF IU per IU FVIII:C); Haemate-P with a ratio of 2.5:1 and Hemofil-M containing only trace amounts of VWF. In addition, the recombinant FVIII concentrate Kogenate Bayer containing no VWF was included. Inhibitor titres and the capacity to generate thrombin were measured. A statistically significant difference in measured titres was found with the highest titres recorded against Hemofil-M. The inhibitor titres needed to inhibit 50% maximum thrombin generation were the lowest for Kogenate Bayer and the highest and similar for Fanhdi and Haemate-P with intermediate titres needed for inhibition of Hemofil-M. In this study, the thrombin generation assay provides additional indications for the role of VWF in the treatment of patients with inhibitors. The VWF-containing concentrates Fanhdi and Haemate-P, added to FVIII-deficient plasma with the presence of inhibitor, generate more thrombin than do the purified concentrates Hemofil-M and Kogenate Bayer.
Salvagno
G L
GL
Department of Clinical Chemistry, Verona University Hospital, Verona, Italy.
Astermark
J
J
Ekman
M
M
Franchini
M
M
Guidi
G C
GC
Lippi
G
G
Poli
G
G
Berntorp
E
E
D000937:Antigen-Antibody Reactions; D019774:Blood Coagulation Factor Inhibitors / Q000378:metabolism*; D001780:Blood Coagulation Tests; D003029:Coagulants / Q000494:pharmacology*; D018604:Epitope Mapping; D005169:Factor VIII / Q000494:pharmacology*; D006467:Hemophilia A / Q000097:blood*; D006801:Humans; D007518:Isoantibodies / Q000378:metabolism*; D018709:Statistics, Nonparametric; D013917:Thrombin / Q000096:biosynthesis*; D014841:von Willebrand Factor / Q000494:pharmacology
D019774:Blood Coagulation Factor Inhibitors; D003029:Coagulants; D007518:Isoantibodies; D014841:von Willebrand Factor; C078147:F8 protein, human; D005169:Factor VIII; D013917:Thrombin