A new report of <scp>FVII</scp>‐inhibitor in a patient suffering from severe congenital <scp>FVII</scp> deficiency

Borhany, Munira; Delbes, C.; Giansily‐Blaizot, Muriel; Zubair, Mohammad; Ahmed, Muzzafar; Fatima, Naveena; Shamsi, Tahir

doi:10.1111/hae.12708

Cited by 7 publications

(4 citation statements)

References 10 publications

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“…Thus, the patient might have an FVII gene variation that resulted in the antibody response due to the ‘foreignness’ of BAY 86‐6150 detected by his T‐cell repertoire. Reports of patients developing FVII‐specific neutralizing antibodies are rare , and to date, no studies have shown a correlation between FVII gene polymorphisms and immunogenicity in patients treated with rFVIIa.…”

Section: Discussionmentioning

confidence: 99%

TRUST trial: BAY 86‐6150 use in haemophilia with inhibitors and assessment for immunogenicity

et al. 2016

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Introduction:The most serious and challenging complication of haemophilia treatment is development of inhibitors to replacement factors VIII or IX. Innovative therapies currently being explored for patients with haemophilia and inhibitors include BAY 86-6150, a modified recombinant activated factor VII (FVIIa). Immunogenicity remains a substantial barrier in this endeavour. Aim: To present safety and efficacy results of the BAY 86-6150 study in patients with inhibitors and report detailed analysis of epitope mapping in a patient who developed anti-BAY 86-6150 antibodies. Methods: Patients aged 12-62 years with moderate or severe haemophilia A or B were eligible for the phase 3 TRUST trial if they had a history of high-titre inhibitors. Four escalating doses of BAY 86-6150 (6.5, 20, 50, 90 lg kg À1 ) were planned with ≥10 patients per dose level. Bleeding episodes were treated with BAY 86-6150. Development of anti-BAY 86-6150 antibodies was considered a serious adverse event. Results: TRUST was discontinued after one patient in the 6.5-lg kg À1 cohort developed anti-BAY 86-6150 neutralizing antibodies following three exposures. The anti-BAY 86-6150 antibodies crossreacted with and neutralized wild-type FVIIa (WT-FVIIa). Post hoc epitope mapping using peripheral blood mononuclear cells from the responding patient found that none of the 14 peptides unique to BAY 86-6150 were recognized by the patient's T cells, but strong responses were detected against 2 WT-FVIIa peptides. Conclusion: In the single patient with haemophilia A who developed anti-BAY 86-6150 antibodies, results of Tcell epitope mapping indicated BAY 86-6150 was no more immunogenic than WT-FVIIa.

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Section: Discussionmentioning

confidence: 99%

TRUST trial: BAY 86‐6150 use in haemophilia with inhibitors and assessment for immunogenicity

et al. 2016

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“…72 Also, successful prophylactic rFVIIa in a patient with inherited FVII deficiency with inhibitors to FVII was reported by Tokgoz and colleagues, 68 suggesting a possible weak affinity of this alloantibody to rFVIIa. By contrast, Borhany and colleagues 71 reported a FVII inhibitor case who did not respond to rFVIIa therapy despite extensive immunosuppressive (methylprednisolone and cyclophosphamide) treatment. The largest experience is that by Batorova and colleagues on behalf of the STER (Seven Treatment Evaluation Registry) study group, 70 who detected FVII inhibitors in 2.6% (3/115) of patients in the registry.…”

Section: Anti-fvii Alloantibodiesmentioning

confidence: 93%

“…30 Thirteen inhibitor cases have been reported so far in eight studies, following use of either plasma-derived or rFVII products. [65][66][67][68][69][70][71][72] In a prospective study of 101 spontaneous or traumatic bleeds occurring in 75 patients with congenital FVII deficiency, two inhibitors were detected in two repeatedly treated patients (one post-plasma-derived FVII, one post-rFVIIa). 67 See and colleagues 72 reported the case of FVII inhibitor development following liver transplantation in a 5-yearold girl with severe congenital FVII deficiency.…”

Section: Anti-fvii Alloantibodiesmentioning

confidence: 99%

Inhibitors in Patients with Congenital Bleeding Disorders Other Than Hemophilia

Franchini¹,

Marano²,

Mengoli³

et al. 2017

Semin Thromb Hemost

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The most worrying complication of replacement therapy for severe hemophilia A and B is currently the occurrence of inhibitory alloantibodies against infused factor VIII and factor IX, respectively. Inhibitors compromise the management of hemorrhage in affected patients, with a considerable increase in complications, disability, and costs. While these alloantibodies have been extensively studied in the past years in hemophilia A and B, those occurring in patients with other inherited bleeding disorders are less well characterized and still poorly understood, mostly due to the rarity of these hemorrhagic conditions. This narrative review will deal with inhibitors arising in patients with inherited bleeding disorders other than "classical" hemophilia, focusing in particular on those developing in patients with congenital deficiency of coagulation factor V, factor VII, factor XI, and factor XIII.

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“…Noted to have inhibitors at 1 month old and treated by rFVIIa. 12 Borhany et al [13]. Female/8 years old Could not identify any mutation in the coding regions of F7 and no large rearrangement (both parents had FVII:C levels below 50%)…”

Section: Case Reportmentioning

confidence: 99%

Inhibitor development after liver transplantation in congenital factor VII deficiency

et al. 2016

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Congenital factor VII (FVII) deficiency is the commonest type of the rare bleeding disorders. Very few cases of congenital FVII deficiency developed inhibitor and liver transplant is considered as definitive treatment. In the literature, twelve patients with congenital FVII deficiency developed inhibitors. Two had spontaneous resolution of inhibitors and one did not respond to high dose recombinant factor VIIa (rFVIIa) and died. Regarding liver transplant in congenital FVII patients, seven patients underwent liver transplant with good prognosis. We report a 5-year-old girl with confirmed severe congenital FVII deficiency since neonatal period. She suffered from recurrent intracranial bleeding despite rFVIIa replacement. After auxiliary liver transplant at the age of 4, she continued to show persistent deranged clotting profile and was found to have inhibitor towards FVII. Interestingly, she was still responsive to rFVIIa replacement.

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A new report of FVII‐inhibitor in a patient suffering from severe congenital FVII deficiency

Cited by 7 publications

References 10 publications

TRUST trial: BAY 86‐6150 use in haemophilia with inhibitors and assessment for immunogenicity

TRUST trial: BAY 86‐6150 use in haemophilia with inhibitors and assessment for immunogenicity

Inhibitors in Patients with Congenital Bleeding Disorders Other Than Hemophilia

Inhibitor development after liver transplantation in congenital factor VII deficiency

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