Course of Inhibitors in mild Hemophilia A with and without Immune Tolerance Treatment

2002 ◽  
pp. 47-52
Author(s):  
H. Lenk ◽  
F. Kertzscher
Keyword(s):  
Immune Tolerance ◽  
Hemophilia A

Benefits of prophylactic emicizumab in enhancing immune tolerance induction in a boy with hemophilia A and very high inhibitor titer

2021 ◽  
Author(s):  
Nongnuch Sirachainan ◽  
Ampaiwan Chuansumrit ◽  
Surapan Parapakpenjune ◽  
Pakawan Wongwerawattanakoon ◽  
Surapong Lertthammakiat ◽  
...  
Keyword(s):  
Immune Tolerance ◽  
Hemophilia A ◽  
Tolerance Induction ◽  
Immune Tolerance Induction ◽  
Inhibitor Titer ◽  
Very High

scholarly journals IgG subclasses of anti-FVIII antibodies during immune tolerance induction in patients with hemophilia A

2008 ◽  
Vol 142 (4) ◽  
pp. 644-652 ◽  
Author(s):  
Pauline M. W. van Helden ◽  
H. Marijke van den Berg ◽  
Samantha C. Gouw ◽  
Paul H. P. Kaijen ◽  
Marleen G. Zuurveld ◽  
...  
Keyword(s):  
Immune Tolerance ◽  
Hemophilia A ◽  
Tolerance Induction ◽  
Igg Subclasses ◽  
Immune Tolerance Induction

scholarly journals Anti-A2 and anti-A1 domain antibodies are potential predictors of immune tolerance induction outcome in children with hemophilia A

2015 ◽  
Vol 13 (4) ◽  
pp. 540-547 ◽  
Author(s):  
P. Lapalud ◽  
C. Rothschild ◽  
E. Mathieu-Dupas ◽  
J. Balicchi ◽  
Y. Gruel ◽  
...  
Keyword(s):  
Immune Tolerance ◽  
Hemophilia A ◽  
Tolerance Induction ◽  
Immune Tolerance Induction ◽  
A1 Domain

Immune Tolerance in Two High Responder, Severe Hemophilia A Patients with Inhibitors: The Importance of High Doses and the Duration of the Treatment

Vox Sanguinis ◽  
1996 ◽  
Vol 70 (1) ◽  
pp. 72-73 ◽  
Author(s):  
N. Ciavarella ◽  
M. Schiavoni ◽  
A. Fasano ◽  
M.G. Giliberti ◽  
C. Ettorre ◽  
...  
Keyword(s):  
Immune Tolerance ◽  
Hemophilia A ◽  
High Responder ◽  
Severe Hemophilia ◽  
High Doses

Immune Tolerance in Two High Responder, Severe Hemophilia A Patients with Inhibitors: The Importance of High Doses and the Duration of the Treatment

Vox Sanguinis ◽  
1996 ◽  
Vol 70 ◽  
pp. 72-73
Author(s):  
N. Ciavarella ◽  
M. Schiavoni ◽  
A. Fasano ◽  
M. G. Giliberti ◽  
C. Ettorre ◽  
...  
Keyword(s):  
Immune Tolerance ◽  
Hemophilia A ◽  
High Responder ◽  
Severe Hemophilia ◽  
High Doses

Long-Term Venous Access Catheters and Infections in Patients with Severe Hemophilia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4117-4117
Author(s):  
Janet A. Harrison ◽  
Jerry S. Powell
Keyword(s):  
Immune Tolerance ◽  
Hemophilia A ◽  
Significant Risk ◽  
Clinical Decision ◽  
Primary Prophylaxis ◽  
Venous Access ◽  
Secondary Prophylaxis ◽  
Catheter Placement ◽  
Severe Hemophilia

Abstract Treatment of hemophilia A or B with factor concentrates requires uncomplicated venous access, and frequently this access uses venous access catheters, which have been associated with increased frequency of thrombophlebitis and catheter related infections. Reports have estimated the incidence of infection as 8.3% to 55%. A prospective multi-center study was undertaken to determine the rates of these complications associated with venous access catheters in patients with severe hemophilia. Inclusion criteria were: severe hemophilia, age 6 months to 70 years, and non-emergent need for a long-term venous access catheter. Excluded were catheters inserted for less than 28 days or in a femoral site, and other medical conditions compromising expected survival. 53 subjects (48 hemophilia A, 5 hemophilia B) were enrolled by nine hemophilia treatment centers, with 3 subjects receiving repeat catheter insertions, for a total of 56 catheter experiences. Factor replacement was given to all subjects during catheter placement. Families were trained in catheter use according to individual center practices, and each subject was followed at least monthly in the clinic or by telephone. 54 catheters were placed by a physician in an operating room under sterile conditions; antibiotics were used for catheter placement for 18 subjects. The ages at placement ranged from 10 months to 59 years (mean 8.9 years). Most of the Catheter types were Port-a-Cath (n = 43), 6 Broviac, 4 Hickman, and 3 PICC. The reasons for the catheters varied: primary prophylaxis, 10, secondary prophylaxis, 23, immune tolerance, 17, and for treatment after surgery or trauma, 6. Five subjects were positive for hepatitis C, 2 subjects for hepatitis B, and one for HIV. Of the 53 subjects, 10 have had catheter related infections. The infections were detected 19 to 762 days after catheter insertion (mean 272.7 days). Two subjects had recurrent infections, 4 and 3 respectively. The ages of the subjects at the time of infection ranged from 1.8 to 13.9 years old (mean = 5 years). The peripheral blood cultures and the catheter tip (if removed) cultures revealed a variety of different bacteria and one fungus (candida albicans). Perhaps surprisingly, staphylococcus epidermidis was found in only 2 subjects, and no case of s. aureus was detected. Klebsiella was cultured from 3 subjects who experienced infections. No subjects died during the study. Eight catheters were removed for reasons determined by the responsible clinician: 6 for infection, 1 by accident, 1 was no longer needed. Nine of the 10 subjects with infections received antibiotics. Of the 6 Broviacs, 2 subjects experienced infections (33%). Of the 43 Port-a-Caths, 8 subjects experienced infections (18.6%). The 2 subjects with repeated infections both had Port-a-Caths, and the first infections occurred at 354 and 120 days, respectively. Of the 17 subjects on immune tolerance, 2 subjects experienced infections (not significantly different from the larger cohort). No subjects experienced thrombophlebitis or other catheter failure. In summary, the results of this study demonstrate that long-term venous access catheter use in patients with severe hemophilia: 1) is associated with significant risk of catheter related infections, particularly in children, 2) that these infections can be managed clinically in most cases, with appropriate clinical monitoring, and, 3) the risk of thrombophlebitis is quite low. These data should assist to evaluate the risks and benefits of the clinical decision to use venous access catheters in patients with severe hemophilia.

Reduction of Anti-FVIII Inhibitor Titers in Hemophilic Mice Infused with Syngeneic Apoptotic Cells Expressing a Human FVIII Transgene.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 216-216
Author(s):  
Rui-Jun Su ◽  
Laura Stewart ◽  
Steven W. Pipe ◽  
Neil C. Josephson
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Antibody Titer ◽  
Immune Tolerance ◽  
Hemophilia A ◽  
Apoptotic Cell ◽  
High Titer ◽  
T Cell Proliferation ◽  
Apoptotic Cells ◽  
Proliferation Assays

Abstract Approximately 30% of patients with severe hemophilia A develop neutralizing antibodies (inhibitors) to factor VIII (FVIII). Frequently, the inhibitors that develop are persistent and of sufficiently high titer that infusion of FVIII concentrates are ineffective for the control of bleeding episodes. At present the only method for elimination of high titer inhibitors is Immune Tolerance Induction (ITI) by exposing patients to repeated FVIII doses. However, it is extremely expensive and takes many months to complete. There is a need to develop quicker, cheaper, and more reliable protocols for inducing tolerance in patients with high titer FVIII inhibitors, and of preventing their occurrence in patients at high risk. In a non-inflammatory environment, autologous apoptotic cells are processed by immature, non-activated dendritic cells (DCs) capable of initiating peripheral immune tolerance through the stimulation of different classes of regulatory T cells. Furthermore, it has been demonstrated that antigen specific tolerance can be induced by delivery of a foreign protein within dying syngeneic cells (Liu et al, J Exp Med196: 1091, 2002). We hypothesize that immune tolerance to FVIII can be induced by the infusion of apoptotic autologous cells engineered to carry a FVIII expression vector. We generated a fibroblast cell line from a tail snip of a 129Sv-FVIIIKO mouse and transduced the cells with a foamy virus vector expressing a B-domain deleted human FVIII construct. Expression of human FVIII was detected by ELISA in the supernatant of cultured transduced fibroblasts. These transduced cells were induced to apoptosis by serum starvation for 24–30 hr prior to infusion into 129Sv-FVIIIKO mice. Treated mice received two weekly doses of 1x107 serum starved transduced fibroblasts. Control mice were infused with culture media alone. Ten days after the final infusion, experimental and control mice were challenged with 4 weekly intravenous doses of 0.2 μg albumin free recombinant human FVIII (ADVATE). Ten days after the final dose of ADVATE blood samples were collected and evaluated for inhibitor titer by Bethesda assay and for total anti-FVIII antibody titer by ELISA. Three weeks later, T cell proliferation assays were performed on samples from mice in each group. The mice that received apoptotic cells had lower inhibitor titers than controls, 156.7 ± 82.7 BU/ml (n = 6) versus 331.3 ± 183.9 BU/ml (n = 11) (p = 0.017, Welch’s t-test). However, total antibody titer levels determined by ELISA were not significantly different between the two groups. T-cell proliferation assays also showed a reduced T cell response in the apoptotic cell treated mice with a stimulation index that was half that seen in the controls. Our data show that inhibitor titers and T cell responses in hemophilia A mice challenged by albumin free recombinant FVIIII can be reduced by the prior infusion of apoptotic syngeneic cells transduced with a human FVIII expressing vector. Future work will focus on optimizing apoptotic cell delivery protocols to maximally suppress the immune response to FVIII and on elucidating the mechanisms responsible for our findings. Figure Figure

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