Immune tolerance induction therapy for patients with hemophilia A and FVIII inhibitors particularly using low-dose regimens

2011 ◽  
Vol 57 (6) ◽  
pp. 1029-1033 ◽  
Author(s):  
Pei-Chin Lin ◽  
Yu-Mei Liao ◽  
Shih-Pien Tsai ◽  
Tai-Tsung Chang
Keyword(s):  
Induction Therapy ◽  
Immune Tolerance ◽  
Low Dose ◽  
Hemophilia A ◽  
Tolerance Induction ◽  
Immune Tolerance Induction

scholarly journals Acquired Hemophilia A: A Frequently Overlooked Autoimmune Hemorrhagic Disorder

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Yoshihiko Sakurai ◽  
Tomohiro Takeda
Keyword(s):  
Induction Therapy ◽  
Immune Tolerance ◽  
Hemophilia A ◽  
Tolerance Induction ◽  
High Dose ◽  
Bleeding Tendency ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia ◽  
Acute Hemorrhage ◽  
Immune Tolerance Induction

Acquired hemophilia A (AHA) is a rare hemorrhagic disease in which autoantibodies against coagulation factor VIII- (FVIII-) neutralizing antibodies (inhibitors) impair the intrinsic coagulation system. As the inhibitors developed in AHA are autoantibodies, the disease may have an autoimmune cause and is often associated with autoimmune disease. Although acute hemorrhage associated with AHA may be fatal and is costly to treat, AHA is often unrecognized or misdiagnosed. AHA should thus be considered in the differential diagnosis particularly in postpartum women and the elderly with bleeding tendency or prolonged activated partial thromboplastin time. Cross-mixing tests and measurement of FVIII-binding antibodies are useful to confirm AHA diagnosis. For treatment of acute hemorrhage, hemostatic therapy with bypassing agents should be provided. Unlike in congenital hemophilia A with inhibitors, in which immune tolerance induction therapy using repetitive infusions of high-dose FVIII concentrates is effective for inhibitor eradication, immune tolerance induction therapy has shown poor efficacy in treating AHA. Immunosuppressive treatment should thus be initiated to eradicate inhibitors as soon as the diagnosis of AHA is confirmed.

scholarly journals Low-Dose Immune Tolerance Induction for Hemophilia a Children with Poor-Risk High-Titer Inhibitors

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1122-1122
Author(s):  
Zekun Li ◽  
Zhenping Chen ◽  
Xiaoling Cheng ◽  
Xinyi Wu ◽  
Li Gang ◽  
...  
Keyword(s):  
Success Rate ◽  
Board Of Directors ◽  
Immune Tolerance ◽  
Low Dose ◽  
Hemophilia A ◽  
Tolerance Induction ◽  
Advisory Committees ◽  
Immune Tolerance Induction ◽  
Inhibitor Titer

Background: Low-dose immune tolerance induction (ITI) +/- immunosuppression as a practical ITI strategy in China showed a relatively satisfactory success rate and economic advantages in pilot study. However, the outcome still needs to be verified by larger cohort. Aim: To report the efficacy of this low-dose ITI +/- immunosuppression strategy in hemophilia A children ≥ 10 BU. Methods: This was a single center, prospective study in 53 hemophilia A subjects from Sep 2016 to Apr 2019. All subjects having ≥ 10 BU receiving ~50IU/kg FVIII every other day using domestic intermediate purity pdFVIII/VWF products, either alone or in combination with rituximab and prednisone judging by inhibitors and ITI response. Results: Finally, 46 subjects received this strategy at a median of 3.2 (IQR, 2.3-6.5) years old, their pre-ITI inhibitor titer was median 30.0 (range, 10.1-416) BU. Analysis at median 15.1 (range 3.0-34.4) months follow-up, success (inhibitor <0.6BU) was achieved in 32 (69.6%) subjects, partial success (inhibitor <5BU but >0.6BU) in 11 (23.9%) subjects, and failure in 5 (10.9%) subjects. Between subjects administered ITI-alone and ITI- immunosuppression, no significant difference was observed in time to success (median 8.5; IQR 6.7-11.7 vs 10.2; IQR 5.1-25.1, P=0.164). The mean monthly bleeding rate on ITI was 0.49 which declined 59.3% compared with pre-ITI period. Subjects administered ITI-immunosuppression (0.54 ± 0.46) was higher than ITI-alone (0.42 ± 0.69) although with no significantly difference (P=0.089). Seven (21.9%) subjects experienced inhibitor recurrence, 4 subjects treated with ITI-alone, 3 with ITI-immunosuppression. Recurrence occurred at a median of 4.8 (range, 2.8-10.8) months after successful ITI with inhibitor titer transiently rising to median 0.7 (range, 0.7-1.5) BU. Conclusion: This low-dose ITI +/- immunosuppression therapy in subjects with pre-ITI inhibitor ≥ 10 BU showed a success rate similar to other high/intermediate-dose regimen for the whole inhibitor patients. The subjects treated with ITI-immunosuppression did not showed higher recurrence at present, while a longer time follow-up is still needed. Disclosures Poon: Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bioverativ/Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; World Federation of Hemophilia: Other: Not-for-profit organization affiliation: volunteer ; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Participation in sponsored research; CSL-Behring: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Grant Funding; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Grant Funding; Takeda/Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees; Octapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Low-dose immune tolerance induction in hemophilia A patients with inhibitors

Blood ◽  
1995 ◽  
Vol 86 (3) ◽  
pp. 983-988 ◽  
Author(s):  
EP Mauser-Bunschoten ◽  
HK Nieuwenhuis ◽  
G Roosendaal ◽  
HM van den Berg
Keyword(s):  
Factor Viii ◽  
Immune Tolerance ◽  
Low Dose ◽  
Hemophilia A ◽  
Tolerance Induction ◽  
Immune Tolerance Induction ◽  
Inhibitor Development ◽  
Two Factors ◽  
Inhibitor Level ◽  
Dose Factor

Abstract In patients with hemophilia A and inhibitory alloantibodies against factor VIII, various dosage schedules are used to obtain immune tolerance. In this study, we have evaluated the results of 13 years of low-dose immune tolerance induction and factors that are predictive of a positive result. The effect of immune tolerance induction in relation to age at inhibitor development, number of exposure days, age at start of therapy, maximum inhibitor titer, factor VIII products involved, and virologic status were determined. We evaluated 24 patients with severe hemophilia A and inhibitors who were treated with regular infusions with low-dose (25 U/kg every other day) factor VIII to obtain immune tolerance. In 21 of 24 patients (87%), immune tolerance induction was successful. The response time was determined by two factors: the highest inhibitor level and the age at inhibitor development. In patients with maximum inhibitor levels of less than 40 Bethesda units (BU)/mL, immune tolerance was obtained sooner than in patients with inhibitor levels exceeding 40 BU/mL (P = .005). Patients in whom an inhibitor developed before the age of 2.5 years also tended to have a quick immune response (P = .014). Immune tolerance with low-dose factor VIII is often successful in hemophilia A patients with inhibitors. Young children and patients with maximum inhibitors of less than 40 BU/mL show a relatively rapid response.

scholarly journals Low-dose immune tolerance induction in hemophilia A patients with inhibitors

Blood ◽  
1995 ◽  
Vol 86 (3) ◽  
pp. 983-988 ◽  
Author(s):  
EP Mauser-Bunschoten ◽  
HK Nieuwenhuis ◽  
G Roosendaal ◽  
HM van den Berg
Keyword(s):  
Factor Viii ◽  
Immune Tolerance ◽  
Low Dose ◽  
Hemophilia A ◽  
Tolerance Induction ◽  
Immune Tolerance Induction ◽  
Inhibitor Development ◽  
Two Factors ◽  
Inhibitor Level ◽  
Dose Factor

In patients with hemophilia A and inhibitory alloantibodies against factor VIII, various dosage schedules are used to obtain immune tolerance. In this study, we have evaluated the results of 13 years of low-dose immune tolerance induction and factors that are predictive of a positive result. The effect of immune tolerance induction in relation to age at inhibitor development, number of exposure days, age at start of therapy, maximum inhibitor titer, factor VIII products involved, and virologic status were determined. We evaluated 24 patients with severe hemophilia A and inhibitors who were treated with regular infusions with low-dose (25 U/kg every other day) factor VIII to obtain immune tolerance. In 21 of 24 patients (87%), immune tolerance induction was successful. The response time was determined by two factors: the highest inhibitor level and the age at inhibitor development. In patients with maximum inhibitor levels of less than 40 Bethesda units (BU)/mL, immune tolerance was obtained sooner than in patients with inhibitor levels exceeding 40 BU/mL (P = .005). Patients in whom an inhibitor developed before the age of 2.5 years also tended to have a quick immune response (P = .014). Immune tolerance with low-dose factor VIII is often successful in hemophilia A patients with inhibitors. Young children and patients with maximum inhibitors of less than 40 BU/mL show a relatively rapid response.

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