Absence of Inhibitors in Previously Untreated Patients with Severe Haemophilia A after Exposure to a Single Intermediate Purity Factor VIII Product

1997 ◽  
Vol 78 (03) ◽  
pp. 1027-1029 ◽  
Author(s):  
T T Yee ◽  
M D Williams ◽  
F G H Hill ◽  
C A Lee ◽  
K J Pasi
Keyword(s):  
Factor Viii ◽  
High Purity ◽  
Specific Activity ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
True Incidence ◽  
Conventional Fractionation ◽  
Heat Treated ◽  
Recombinant Fviii ◽  
Von Willebrand

SummaryUse of high purity and recombinant factor VIII (FVIII) concentrates has been thought to be associated with an increased incidence of FVIII inhibitors in patients with severe haemophilia A. Comparison with comparable historical control groups has suggested that the true incidence of inhibitors in patients with severe haemophilia A was ~20-25%, similar to the incidence seen with new high purity and recombinant FVIII products.We have conducted a study of inhibitor development in a cohort of 37 boys with severe haemophilia A (VIII: C <2 u/dl) exposed only to a single FVIII concentrate (BPL 8Y) with no previous blood or blood product exposure. This factor VIII concentrate is an intermediate purity product with a specific activity of ~2 IU/mg protein and contains well preserved von Willebrand factor multimers. It is manufactured by conventional fractionation technologies and terminally dry heat treated at 80° C for 72 h.

Pharmacokinetics of Optivate®, a high-purity concentrate of factor VIII with von Willebrand factor, in patients with severe haemophilia A

Haemophilia ◽  
2010 ◽  
Vol 17 (2) ◽  
pp. 185-190 ◽  
Author(s):  
A. DMOSZYNSKA ◽  
A. HELLMANN ◽  
T. BAGLIN ◽  
D. O’SHAUGNESSY ◽  
J. TRELINSKI ◽  
...  
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
High Purity ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Von Willebrand ◽  
Willebrand Factor

scholarly journals Desmopressin treatment combined with clotting factor VIII concentrates in patients with non-severe haemophilia A: protocol for a multicentre single-armed trial, the DAVID study

BMJ Open ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. e022719 ◽  
Author(s):  
Lisette M Schütte ◽  
Marjon H Cnossen ◽  
Reinier M van Hest ◽  
Mariette H E Driessens ◽  
Karin Fijnvandraat ◽  
...  
Keyword(s):  
Factor Viii ◽  
Combination Treatment ◽  
Bleeding Risk ◽  
Clotting Factor ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Registration Number ◽  
Concentrate Treatment ◽  
Factor Viii Concentrates ◽  
Von Willebrand

IntroductionHaemophilia A is an inherited bleeding disorder characterised by factor VIII (FVIII) deficiency. In patients with non-severe haemophilia A, surgery and bleeding are the main indications for treatment with FVIII concentrate. A recent study reported that standard dosing frequently results in FVIII levels (FVIII:C) below or above FVIII target ranges, leading to respectively a bleeding risk or excessive costs. In addition, FVIII concentrate treatment carries a risk of development of neutralising antibodies. An alternative is desmopressin, which releases endogenous FVIII and von Willebrand factor. In most patients with non-severe haemophilia A, desmopressin alone is not enough to achieve FVIII target levels during surgery or bleeding. We hypothesise that combined pharmacokinetic (PK)-guided administration of desmopressin and FVIII concentrate may improve dosing accuracy and reduces FVIII concentrate consumption.Methods and analysisIn the DAVID study, 50 patients with non-severe haemophilia A (FVIII:C ≥0.01 IU/mL) with a bleeding episode or undergoing surgery will receive desmopressin and FVIII concentrate combination treatment. The necessary dose of FVIII concentrate to reach FVIII target levels after desmopressin administration will be calculated with a population PK model. The primary endpoint is the proportion of patients reaching FVIII target levels during the first 72 hours after start of the combination treatment. This approach was successfully tested in one pilot patient who received perioperative combination treatment.Ethics and disseminationThe DAVID study was approved by the medical ethics committee of the Erasmus MC. Results of the study will be communicated trough publication in international scientific journals and presentation at (inter)national conferences.Trial registration numberNTR5383; Pre-results.

scholarly journals Influence of blood group, von Willebrand factor levels, and age on factor VIII levels in non‐severe haemophilia A

2020 ◽  
Vol 18 (5) ◽  
pp. 1081-1086
Author(s):  
Judit Rejtő ◽  
Oliver Königsbrügge ◽  
Ella Grilz ◽  
Stefanie Hofer ◽  
Lisa‐Marie Mauracher ◽  
...  
Keyword(s):  
Factor Viii ◽  
Blood Group ◽  
Von Willebrand Factor ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Von Willebrand ◽  
Willebrand Factor

scholarly journals Clinical assessment of Optivate®, a high-purity concentrate of factor VIII with von Willebrand factor, in the management of patients with haemophilia A

Haemophilia ◽  
2011 ◽  
Vol 17 (3) ◽  
pp. 456-462 ◽  
Author(s):  
A. DMOSZYNSKA ◽  
K. KULICZKOWSKI ◽  
A. HELLMANN ◽  
J. TRELINSKI ◽  
J. KLOCZKO ◽  
...  
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Clinical Assessment ◽  
High Purity ◽  
Haemophilia A ◽  
Von Willebrand ◽  
Willebrand Factor

Immune Tolerance with a High Purity Plasma Derived Factor VIII Containing Von Willebrand Factor in Haemophilia A Patients with High Responding Inhibitors.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3096-3096
Author(s):  
Benoit Polack ◽  
Philippe Beurrier ◽  
Chantal Rothschild ◽  
Frédérique Orsini ◽  
Albert Faradji ◽  
...  
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Immune Tolerance ◽  
High Purity ◽  
Cumulative Exposure ◽  
Treatment Schedule ◽  
Haemophilia A ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Partial Success

Abstract We report on 8 patients with severe haemophilia A and high responding anti-factor VIII (FVIII) inhibiting antibody in whom immune tolerance (IIT) was induced with a high purity plasma derived FVIII containing 14 to 20 IU/ml of von Willebrand factor (VWF) as a stabiliser. Their median ages at the diagnosis of the inhibitor was 10.6 months and ranged from 5 months to 9 years. At the onset of IIT, the median age was 1 year and 9 months and ranged from 9 months to 24.5 years. The median cumulative exposure days (CED) was 18.5 days and varied from 8 to 81 days when inhibitor was detected. The maximum level of inhibitor reached from 10 to 500 Bethesda Units (BU) with a median of 22.5 BU. Before inhibitor diagnosis 6 patients had received plasma derived high purity FVIII and 2 had received recombinant FVIII. The treatment schedule started with 50 IU/kg to 200 IU/kg FVIII every day. The time to reach an inhibitor level <1 BU was available for 5 patients; its median was 142 days and varied from 75 to 216 days. The treatment was considered successful when either the recovery or the half life of FVIII was normalized. The outcome was successful in 7 out of the 8 patients (87.5 %) who are now receiving FVIII concentrates either on demand or prophylactically. The last patient was considered as a partial success since the titre of his inhibitor was 0.8 BU and he could be treated by FVIII concentrates when needed. No definite IIT failure was observed in this cohort of patients. Since all the patients are by now back to FVIII treatment we can consider having a 100% success in IIT in this small cohort of patients. Therefore, despite the size of our cohort of patients, our study shows that high purity FVIII stabilized by VWF is an effective drug for the eradication of anti-FVIII inhibitors through induction of immune tolerance. Patients data Patient Age at FVIII 1st infussion Age at inhibitor diagnosis CED at inhibitor diagnosis Age at IIT Inhibitor max.titre (BU) Time (d) <1 BU IIT results N.A.; not available 1 9m 1y 9 1y 3m 52 93 Success 2 2d 4y 3m 81 4y 3m 21 N.A. Success 3 8y 10m 9y 33 24y 6m 30 N.A. Success 4 8m 10m 28 1y 8m 24 75 Success 5 8m 8.5m 8 9m 14.5 - Partial success 6 1y 1m 1y 10m 21 3y 1m 10 142 Success 7 6m 9m 10 11m 20 216 Success 8 4m 5m 16 1y 9m 500 176 Success

Von Willebrand Factor Modulates Factor VIII Immunogenicity: Comparative Study of Different Factor VIII Concentrates in a Haemophilia A Mouse Model

2002 ◽  
Vol 88 (08) ◽  
pp. 221-229 ◽  
Author(s):  
Mathias Behrmann ◽  
John Pasi ◽  
Jean-Marie Saint-Remy ◽  
Ronald Kotitschke ◽  
Michael Kloft
Keyword(s):  
Immune Response ◽  
Factor Viii ◽  
Von Willebrand Factor ◽  
Major Complication ◽  
Epidemiological Studies ◽  
Haemophilia A ◽  
Epitope Specificity ◽  
Recombinant Fviii ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryThe development of an immune response towards factor VIII (FVIII) remains the major complication of haemophilia A replacement therapy. Product-related risk factors have recently been identified on the basis of epidemiological studies, but the mechanism is not understood. To this end, various commercially available FVIII concentrates were administered by the IV route to FVIII-knockout mice and the resulting immune response was characterised. Significantly higher inhibitor titres (Bethesda assay) were observed for one recombinant FVIII and one plasma-derived FVIII product depleted in von Willebrand factor (VWF). Inhibitor titres were reduced upon pre-incubation of FVIII with purified VWF. Epitope specificity of anti-FVIII IgG was characterised using FVIII-fragments produced in E. coli. Concentrates with no or reduced VWF-level elicited antibodies recognising predominantly the acidic a1 and a3 regions. Addition of VWF prior to injection also modified the epitope specificity. FVIII concentrates, therefore, show qualitative and quantitative variations in immunogenicity, which are at least partly modulated by VWF.

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