A prospective surveillance study of factor VIII inhibitor development in the Canadian haemophilia A population following the switch to a recombinant factor VIII product formulated with sucrose

Haemophilia ◽  
2008 ◽  
Vol 14 (2) ◽  
pp. 281-286 ◽  
Author(s):  
M. RUBINGER ◽  
D. LILLICRAP ◽  
G. E. RIVARD ◽  
J. TEITEL ◽  
M. CARCAO ◽  
...  
Keyword(s):  
Factor Viii ◽  
Recombinant Factor Viii ◽  
Surveillance Study ◽  
Factor Viii Inhibitor ◽  
Haemophilia A ◽  
Prospective Surveillance ◽  
Inhibitor Development ◽  
Viii Inhibitor ◽  
Viii Product

A Higher than Expected Incidence of Factor VIII Inhibitors in Multitransfused Haemophilia A Patients Treated with an Intermediate Purity Pasteurized Factor VIII Concentrate

1993 ◽  
Vol 69 (02) ◽  
pp. 115-118 ◽  
Author(s):  
Kathelijne Peerlinck ◽  
Jef Arnout ◽  
Jean Guy Gilles ◽  
Jean-Marie Saint-Remy ◽  
Jos Vermylen
Keyword(s):  
Factor Viii ◽  
Randomized Trials ◽  
Specific Factor ◽  
Factor Viii Inhibitor ◽  
Haemophilia A ◽  
Viral Inactivation ◽  
Gradual Decline ◽  
Inhibitor Level ◽  
Factor Viii Concentrates ◽  
Viii Inhibitor

SummaryIn May 1990, 218 patients with haemophilia A regularly attending the Leuven Haemophilia Center were randomly assigned to a group receiving either of two newly introduced factor VIII concentrates: factor VIII-P, an intermediate purity pasteurized concentrate, or factor VIII-SD, a high purity concentrate treated with solvent-detergent for viral inactivation.Patients were followed from May 1990 until October 1991. Between August 1991 and October 1991 a clinically important factor VIII inhibitor was detected in five out of the 109 patients receiving factor VIII-P while none of the 109 patients receiving factor VIII-SD developed such antibodies. All patients acquiring an inhibitor had previously been clinically tolerant to transfused factor VIII with 200 to more than 1,000 days of exposure to factor VIII prior to May 1990. Patients with inhibitors were transfused daily with 30 U factor VIII-SD per kg body weight, which was associated with a gradual decline of the inhibitor level. In all patients the antibodies were relatively slow-acting and predominantly directed towards the light chain of factor VIII.This study demonstrates a higher than expected incidence of factor VIII inhibitors associated with the use of a specific factor VIII concentrate in multitransfused haemophilia A patients. It indicates the usefulness of evaluating newly introduced concentrates in prospective, randomized trials.

Clinical Profile of Haemophilia in a Tertiary Care Hospital in Pune, Maharashtra, India

2021 ◽  
Vol 8 (15) ◽  
pp. 968-971
Author(s):  
Sadiq Yunus Mulla ◽  
Sachin Sitaram Pandit ◽  
Sachin Kisan Shivnitwar
Keyword(s):  
Factor Viii ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Factor Ix ◽  
Clinical Profile ◽  
Factor Viii Inhibitor ◽  
Haemophilia A ◽  
Care Hospital ◽  
Factor Viii Activity ◽  
Viii Inhibitor

BACKGROUND Haemophilia’s are X-linked hereditary blood clotting disorders due to deficiency of factor VIII (haemophilia A) or factor IX (haemophilia B) & also has identical clinical manifestations, screening tests abnormalities and sex-linked genetic transmission. Haemophilia’s result from defects in the factor VIII / IX gene that lead to decreased amount of factor VIII / IX protein, the presence of a functionally abnormal protein, or combination of both. Haemophilia A is a classic example of an X-linked recessive trait. The severity of their bleeding depends on their factor VIII activity level; and, rarely, a woman can have very low factor VIII activity, and present with symptoms of moderate or even severe haemophilia. We wanted to study the clinical profile of patients of haemophilia admitted in a tertiary care hospital. METHODS This is a cross-sectional study enrolling 60 known cases of haemophilia A & B admitted in wards & ICU / attending OPD of a tertiary care hospital. History was obtained in detail & thorough clinical examination was carried out. Precipitating factors for bleeding (spontaneous / minor trauma / major trauma / surgical operation / dental procedure / others), family h / o bleeding were studied in detail. RESULTS Of the total 60 cases of haemophilia, majority (49) of cases were of haemophilia A and 11 cases were of haemophilia B. In the study, majority (28.33 %) of cases belonged to 12 - 20 years age group and the most common presentation was haemarthrosis (61.67 %). 6 patients had factor VIII inhibitor antibodies and all of them were of haemophilia A. CONCLUSIONS Haemarthrosis is the most common clinical presentation of haemophilia and most common cause for haemarthrosis is spontaneous bleeding. Most common joint involved in bleeding was knee joint (target joint). Presence of factor VIII inhibitor antibodies specially in haemophilia A patients is not uncommon. KEYWORDS Haemophilia, Factor VIII, Factor IX

Longitudinal Analysis of Factor VIII Inhibitors in a Previously Untreated Mild Haemophilia A Patient with an Arg593→Cys Substitution

1999 ◽  
Vol 81 (05) ◽  
pp. 723-726 ◽  
Author(s):  
Simone Timmermans ◽  
Ellen Turenhout ◽  
Christine Bank ◽  
Karin Fijnvandraat ◽  
Jan Voorberg ◽  
...  
Keyword(s):  
Factor Viii ◽  
Light Chain ◽  
Longitudinal Analysis ◽  
Factor Viii Inhibitor ◽  
Haemophilia A ◽  
Missense Mutations ◽  
Initial Development ◽  
Inhibitor Development ◽  
Epitope Specificity ◽  
A2 Domain

SummaryRecent studies suggest that certain missense mutations associated with mild to moderate haemophilia A predispose to inhibitor development. In this study, we present a longitudinal analysis of the epitope specificity of an inhibitor that developed in a mild haemophiliac with an Arg593→Cys mutation. Immunoprecipitation studies revealed the presence of antibodies directed towards the light chain and A2 domain of factor VIII. Limited reactivity was observed with metabolically labelled C2 domain. Almost complete inhibitor neutralization was achieved upon addition of A2 domain. Binding of the inhibitor was not affected by the presence of the Arg593→Cys substitution in the recombinant A2 fragment. Evaluation of the epitope specificity of anti-factor VIII antibodies in plasma samples obtained at different time-points of inhibitor development revealed initial development of a low titre inhibitor directed towards the A2 domain and factor VIII light chain. A second period of factor VIII replacement therapy resulted in a dramatic rise in factor VIII inhibitor titre, which maintained their original epitope specificity. Based on the results of this and previous studies (Fijnvandraat et al., 1997; Thompson et al., 1997) it is argued that inhibitor development in patients with the Arg593→Cys mutation may proceed via a similar mechanism.

scholarly journals Marginal zone B cells are critical to factor VIII inhibitor formation in mice with hemophilia A

Blood ◽  
2017 ◽  
Vol 130 (23) ◽  
pp. 2559-2568 ◽  
Author(s):  
Patricia E. Zerra ◽  
Courtney Cox ◽  
W. Hunter Baldwin ◽  
Seema R. Patel ◽  
Connie M. Arthur ◽  
...  
Keyword(s):  
B Cells ◽  
Factor Viii ◽  
Marginal Zone ◽  
Hemophilia A ◽  
Factor Viii Inhibitor ◽  
Marginal Zone B Cells ◽  
Inhibitor Development ◽  
Fviii Inhibitor ◽  
Key Points ◽  
Viii Inhibitor

Key Points FVIII colocalizes with MZ B cells following infusion into hemophilia A mice. Depletion of MZ B cells prevents FVIII inhibitor development in hemophilia A mice.

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