Comparison of Anti-Human and Anti-Porcine Factor VIII Inhibitor Levels in 63 Patients with Severe Haemophilia A

Fiks-Sigaud, M.; Bendelac, L.; Parquet, A.; Verroust, F.; Torchet, M.F.; Berthier, A.M.; Fressinaud, E.; Guerois, C.; Aillaud, M.F.; Boneu, B.; Derlon, A.; Subtil, E.; Bertrand, M.A.; Borg, J.Y.; Laurian, Y.

doi:10.1159/000462354

Cited by 5 publications

(4 citation statements)

References 8 publications

(16 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is a laboratory artefact caused by depletion of factor VIII in the substrate plasma, which may be ‘diluted out’ so that assays of increasing dilutions of the patient's plasma give progressively increasing factor IX, XI and XII levels while having no effect on the uniformly low factor VIII level. The inhibitor titre should be determined using both human and porcine factor VIII because factor VIII auto‐antibodies usually exhibit little inhibitor activity against porcine factor VIII (Kasper, 1991; Fiks‐Sigaud et al , 1993; Morrison et al , 1993). The Bethesda assay may underestimate inhibitor potency in acquired haemophilia because the second‐order reaction kinetics result in the persistence of low levels of factor VIII, even after prolonged incubation.…”

Section: Diagnosis and Investigation Of Inhibitors To Factors VIII Anmentioning

confidence: 99%

THE DIAGNOSIS and MANAGEMENT OF FACTOR VIII and IX INHIBITORS: A GUIDELINE FROM THE UK HAEMOPHILIA CENTRE DOCTORS' ORGANIZATION (UKHCDO)

Hay¹,

Baglin²,

Collins³

et al. 2000

Br J Haematol

View full text Add to dashboard Cite

Section: Diagnosis and Investigation Of Inhibitors To Factors VIII Anmentioning

confidence: 99%

THE DIAGNOSIS and MANAGEMENT OF FACTOR VIII and IX INHIBITORS: A GUIDELINE FROM THE UK HAEMOPHILIA CENTRE DOCTORS' ORGANIZATION (UKHCDO)

Hay¹,

Baglin²,

Collins³

et al. 2000

Br J Haematol

View full text Add to dashboard Cite

“…Inhibitory antibodies (inhibitors) to factor (F) VIII typically exhibit incomplete or absent crossreactivity with porcine FVIII [1–4]. A commercial plasma‐derived porcine FVIII concentrate (Hyate:C; Ipsen Inc., Milford, MA, USA) was effective for 20 years in the management of many inhibitor patients [5–10].…”

Section: Introductionmentioning

confidence: 99%

Neutralization of antifactor VIII inhibitors by recombinant porcine factor VIII

Barrow

Lollar

2006

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

Summary. Background: Inhibitory antibodies to factor (F) VIII (FVIII inhibitors) present a major clinical challenge as a complication of hemophilia A and as acquired autoantibodies in non-hemophiliacs. Porcine FVIII is a potentially useful therapeutic agent because of its low crossreactivity with many inhibitors. Recombinant porcine FVIII (rpFVIII) is undergoing clinical trials in inhibitor patients. Objectives: The goals of this study were to neutralize human FVIII inhibitors in vitro with rpFVIII and to characterize the relationship between recovery of FVIII activity and the antiporcine FVIII inhibitor titer. Methods: rpFVIII was added to 28 antihuman FVIII inhibitor plasmas and assayed either immediately or after a 2 h preincubation at 37°C. The concentration of rpFVIII required for recovery of FVIII activity to 50% of normal (EC 50 ) was determined by polynomial regression analysis and compared with the antiporcine FVIII inhibitor titer measured by Bethesda assay. Results: Six of nine plasmas classified as non-crossreactive by Bethesda assay had detectable inhibitory activity in the FVIII recovery assay. Recovery was decreased following a 2 h preincubation compared with immediate assay for the 19 plasmas with detectable antiporcine FVIII inhibitors. There was a linear relationship between EC 50 and inhibitor titer for plasmas with antiporcine FVIII titers ranging from 0.6 to 10 BU per milliliter in both the immediate and the 2 h preincubation assays. Conclusion: A quantitative method for analysis of inhibitor neutralization in vitro has been developed, which may be useful for comparison with pharmacodynamic studies of rpFVIII in FVIII inhibitor patients and subsequent rational dosing in this patient population.

show abstract

“…Patients with a low inhibitor level of FVIII or FIX, below 10 Bethesda Units (BU) per millilitre of plasma, and especially those with a low anamnestic response, can be given high doses of the coagulation factor concentrate to neutralize the inhibitor and induce immune tolerance (11). Porcine FVIII is an alternative treatment for haemophilia A patients with inhibitors to FVIII as about 25% of inhibitors in patients with haemophilia A do not cross-react with porcine FVIII (12). However, many patients who do not initially have antibodies that cross-react with porcine FVIII eventually develop such antibodies.…”

Section: Introductionmentioning

confidence: 99%

Experience with use of recombinant activated factor VII

2002

View full text Add to dashboard Cite

Recombinant activated factor VII (rFVIIa) has recently been introduced for improving haemostasis in haemophiliac patients developing alloantibodies (inhibitors) to factor VIII (FVIII) or factor IX (FIX). We describe the successful management of haemorrhagia with rFVIIa in five different situations: an episode of surgical bleeding in a patient with haemophilia A and non-surgical haemorrhages in four patients with haemophilia A, acquired haemophilia, congenital severe FV defect and pseudo-acquired haemophilia, respectively. In each case, rFVIIa was effective and safe. There is no doubt that rFVIIa is useful in the therapeutic management of patients with antibodies to FVIII or FIX. However, the treatment is expensive and a cost-effectiveness analysis would be useful.

show abstract

Comparison of Anti-Human and Anti-Porcine Factor VIII Inhibitor Levels in 63 Patients with Severe Haemophilia A

Cited by 5 publications

References 8 publications

THE DIAGNOSIS and MANAGEMENT OF FACTOR VIII and IX INHIBITORS: A GUIDELINE FROM THE UK HAEMOPHILIA CENTRE DOCTORS' ORGANIZATION (UKHCDO)

THE DIAGNOSIS and MANAGEMENT OF FACTOR VIII and IX INHIBITORS: A GUIDELINE FROM THE UK HAEMOPHILIA CENTRE DOCTORS' ORGANIZATION (UKHCDO)

Neutralization of antifactor VIII inhibitors by recombinant porcine factor VIII

Experience with use of recombinant activated factor VII

Contact Info

Product

Resources

About