A large deletion, spanning exons 1 to 25 of F8 gene, and a high‐titer factor VIII inhibitor, in severe hemophilia A

2020 ◽  
Vol 42 (3) ◽  
Author(s):  
Sayed Hamid Mousavi ◽  
Seyed Alireza Mesbah‐Namin ◽  
Sirous Zeinali ◽  
Mohammad Jazebi ◽  
Ali Dabbagh ◽  
...  
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
High Titer ◽  
Large Deletion ◽  
Factor Viii Inhibitor ◽  
Severe Hemophilia ◽  
Viii Inhibitor

Hemodialysis in a patient with severe hemophilia A and factor VIII inhibitor

2016 ◽  
Vol 20 (4) ◽  
pp. E11-E13 ◽  
Author(s):  
Natarajan Gopalakrishnan ◽  
Thiruvengadam Usha ◽  
Balasubramaniyan Thopalan ◽  
Jeyachandran Dhanapriya ◽  
Thanigachalam Dineshkumar ◽  
...  
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Factor Viii Inhibitor ◽  
Severe Hemophilia ◽  
Viii Inhibitor

Significance of Factor VIII Inhibitors by ELISA in Patients with Hemophilia A.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3398-3398
Author(s):  
Jamie R Brewer ◽  
Sandra Harris ◽  
David Green ◽  
Anaadriana Zakarija
Keyword(s):  
Factor Viii ◽  
Functional Status ◽  
Hemophilia A ◽  
Statistical Significance ◽  
Bleeding Event ◽  
Clinical Information ◽  
Prior History ◽  
Factor Viii Inhibitor ◽  
Severe Hemophilia ◽  
Viii Inhibitor

Abstract Background: The Bethesda assay traditionally has been used to detect Factor VIII inhibitors in patients with Hemophilia A, but recent evidence suggests that it is not sensitive to all inhibitors, particularly non-inhibitory or low-titer antibodies. Methods: Patients with Hemophilia A without prior history of inhibitor were recruited. Study questionnaire collected demographic and clinical information, bleeding history and factor usage over the preceding 6 months. Functional status was assessed by the Hemophilia Activities List (HAL). Factor VIII inhibitor was assessed by both the Bethesda assay and Factor VIII inhibitor ELISA (GTI Diagnostics). T-test was performed to assess statistical significance. Results: Data is available for 26 patients, 19 severe, 2 moderate and 7 mild. All subjects had a negative Bethesda assay, but 10 (39%) had a detectable inhibitor by ELISA. 9/10 inhibitor patients had severe hemophilia, while one had mild hemophilia. In severe hemophiliacs, there were no differences in age, HIV status, CD4 count, Hepatitis C positivity or viral load between those with and those without inhibitors. Inhibitors were more frequent in those using plasma-derived concentrates 4/5 (80%), than in those using recombinant products 6/14 (43%), p=0.15. There was no difference in bleeding frequency or functional status in patients with or without inhibitors, although those with inhibitors had more frequent infusions.(Table). In patients on prophylaxis, those with inhibitors had a higher bleeding frequency compared to those without an inhibitor, (p =0.2). 11 patients were not on prophylaxis and had a higher bleeding frequency (p = 0.02) than patients on prophylaxis irrespective of inhibitor presence. However those with inhibitors required more factor doses per bleed compared to those without an inhibitor (4.4 vs. 1.5, p=0.16) even though the mean factor dose was the same (25.3 units/kg vs 25.2 units/kg). Conclusions: The Factor VIII ELISA assay detected inhibitors in 39 % of Hemophilia A patients who had undetectable inhibitors by standard Bethesda assay. This data suggests that these inhibitors may be clinically relevant, given that inhibitor patients who are not on prophylaxis require more doses of factor per bleeding event. Further study is necessary to determine mechanism and clinical significance of these Factor VIII inhibitors. Table. Characteristics of severe hemophilia patients with and without ELISA Factor VIII inhibitor All severe (n=19) Inhibitor (n=9) No inhibitor (n=10) Age 43.4 40.8 45.7 Plasma-derived factor 5 (26.3%) 4 (44.4%) 1 (10%) Total bleeds/6 months 8.6 8.1 9.0 Muscle bleeds/6 months 1.3 0.8 1.7 Joint bleeds/6 months 7.3 7.3 7.3 Factor infusions/6 months 50.9 57.2 45.2 On prophylaxis 8 (42%) 4 (44.4%) 4 (40%) Total bleeds/6 months 4.3 5.8 2.8 Not on prophylaxis 11 (58%) 5 (55.6%) 6 (60%) Total bleeds/6 months 11.7 10 13.2 Factor doses/bleed 2.9 4.4 1.5

Case Report: Development of Factor VIII Inhibitor in a Patient with an Uncommon de novo Mutation in the Factor VIII Gene

2019 ◽  
Vol 141 (3) ◽  
pp. 129-134
Author(s):  
Kirk D. Wyatt ◽  
Lea M. Coon ◽  
Dawn N. Rusk ◽  
Vilmarie Rodriguez ◽  
Deepti M. Warad
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
De Novo ◽  
De Novo Mutation ◽  
Factor Viii Inhibitor ◽  
Severe Hemophilia ◽  
Factor Viii Gene ◽  
Patient Reported ◽  
Viii Inhibitor ◽  
Mixed Ethnicity

The development of factor VIII inhibitors remains a significant clinical challenge in the management of hemophilia A. We present a patient of mixed ethnicity with severe hemophilia A who was found to have a F8 gene hemizygous c.5815G>T mutation resulting in an Ala1939Ser substitution (Ala1920Ser in legacy nomenclature) and possible splice site change that has been reported in only 1 patient previously. He developed an inhibitor shortly after starting replacement recombinant factor VIII (Advate®; Baxalta, Bannockburn, IL, USA) and was successfully treated with immune tolerance therapy. Our report describes the second patient reported to have severe hemophilia due to this mutation and the only case of a factor VIII inhibitor associated with this mutation.

scholarly journals Risk stratification integrating genetic data for factor VIII inhibitor development in patients with severe hemophilia A

PLoS ONE ◽  
2019 ◽  
Vol 14 (6) ◽  
pp. e0218258
Author(s):  
Delphine Bachelet ◽  
Thilo Albert ◽  
Cyprien Mbogning ◽  
Signe Hässler ◽  
Yuan Zhang ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Factor Viii ◽  
Hemophilia A ◽  
Genetic Data ◽  
Factor Viii Inhibitor ◽  
Severe Hemophilia ◽  
Inhibitor Development ◽  
Viii Inhibitor

Incidence of Factor VIII Inhibitor Development in Severe Hemophilia A Patients Treated only with One Brand of Highly Purified Plasma-Derived Concentrate

1995 ◽  
Vol 73 (02) ◽  
pp. 215-218 ◽  
Author(s):  
Claude Guérois ◽  
Yves Laurian ◽  
Chantal Rothschild ◽  
Armelle Parquet-Gernez ◽  
Anne-Marie Duclos ◽  
...  
Keyword(s):  
Factor Viii ◽  
High Purity ◽  
Hemophilia A ◽  
Cumulative Exposure ◽  
Factor Viii Inhibitor ◽  
Severe Hemophilia ◽  
Viral Inactivation ◽  
Inhibitor Development ◽  
Viii Inhibitor ◽  
Low Incidence

SummaryThe incidence of factor VIII inhibitor was studied in a cohort of 56 previously untreated patients with severe hemophilia A (factor VIII below 1 U/dl). They received only one brand of highly purified factor VIII concentrate (HPSD-VIII) prepared by conventional chromatography with a solvent-detergent step for viral inactivation. Followup since the first infusion of HPSD-VIII was from 1 to 76 months (mean = 29) and cumulative exposure days (CED) from 1 to over 100 (median = 26). Five patients (9%) developed an inhibitor after 6 to 19 CED, only one being a high responder (2%), showing a low incidence of inhibitor compared with previous studies using high purity plasma- derived or recombinant products.

scholarly journals The prevalence of factor VIII inhibitor in patients with severe hemophilia-A and its clinical characteristics

2016 ◽  
Vol 45 (4) ◽  
pp. 177 ◽  
Author(s):  
Harijadi Harijadi ◽  
Djajadiman Gatot ◽  
Arwin AP Akib
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Factor Viii Inhibitor ◽  
Severe Hemophilia ◽  
Cross Sectional ◽  
On Demand ◽  
Treat Ment ◽  
Inhibitor Titre ◽  
Chronic Arthropathy ◽  
Viii Inhibitor

Background Hemophilia is a hereditary blood-clotting disorderdue to factor VIII deficiency. Up to this date, the administration offactor VIII in preventing and managing bleeding has been the maintreatment. One of the complications, which may occur due to re-peated administrations of factor VIII, is the formation of factor VIIIantibody (factor VIII inhibitor).Objective To find out the prevalence of severe hemophilia-A withfactor VIII inhibitor and its clinical characteristics.Methods A cross-sectional descriptive study was performed onchildren with severe hemophilia-A at the National Hemophilia CareCentre, Cipto Mangunkusumo Hospital, Jakarta, Indonesia, in June-August 2004.Results Out of 45 children studied, 16 had factor VIII inhibitor withaverage inhibitor titre of 1.15 Bethesda units (BU) (range 0.15-15BU). Most of them (12 patients) had inhibitor titre <5 BU. Chronicarthropathy was found in 17 out of 45 (37%) children with severehemophilia-A, consisting of nine patients from positive inhibitorgroup and 8 patients from negative inhibitor group. Thirty-ninepatients (86%) used an on-demand treatment pattern, among whom15 had positive inhibitor. Among patients receiving prophylactictreatment pattern, only one had positive inhibitor. There were 39patients (86%) treated using cryoprecipitate, among whom factorVIII inhibitor was found in 12, while among those treated with fac-tor VIII concentrate, the inhibitor was positive in 4/6. The averageamount of factor VIII transfused in positive and negative factor VIIIinhibitor groups was similar.Conclusion The prevalence of factor VIII inhibitor in severe he-mophilia-A patients was 35%. Chronic arthropathy occurred moreoften in patients with positive factor VIII inhibitor. Factor VIII inhibi-tor was found more frequently in patients with an on-demand treat-ment pattern and in those using factor VIII concentrate

scholarly journals A Clinical and Experimental Study of Acquired Inhibitors to Factor VIII

Blood ◽  
1965 ◽  
Vol 26 (6) ◽  
pp. 805-818 ◽  
Author(s):  
HAROLD R. ROBERTS ◽  
MARGARET B. SCALES ◽  
JOHN T. MADISON ◽  
WILLIAM P. WEBSTER ◽  
GEORGE D. PENICK
Keyword(s):  
Experimental Study ◽  
Factor Viii ◽  
Mode Of Action ◽  
Exchange Transfusion ◽  
Hemophilia A ◽  
Retroperitoneal Hematoma ◽  
Factor Viii Inhibitor ◽  
Viii Inhibitor ◽  
Potent Factor

Abstract Factor VIII inhibitors which developed in four patients with hemophilia A are described. These inhibitors are apparently specific for Factor VIII and are capable of inducing a transient hemophilic state when injected into dogs. The genesis, properties, and mode of action of these inhibitors can be explained on an immunologic basis and it seems most likely that they represent an antibody to Factor VIII. One hemophilia A patient, with retroperitoneal hematoma and a potent Factor VIII inhibitor, was successfully treated by an exchange transfusion followed by administration of purified porcine Factor VIII.

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