Involvement of the IgE‐basophil system and mild complement activation in haemophilia B with anti‐factor IX neutralizing antibodies and anaphylaxis

Cugno, Massimo; Mancuso, Maria Elisa; Tedeschi, A.; Santagostino, Elena; Lorini, M.; Carbonelli, V.; Peyvandi, Flora; Mannucci, Pier Mannuccio

doi:10.1111/hae.13282

Cited by 9 publications

(6 citation statements)

References 14 publications

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“…Although the patient was able to self-infuse, we decided to treat him in the first Large delections or null mutations 11,12 were reported as associated to high risk of inhibitor development and could explain the appearance of these allo-antibodies also in cases of PTPs after multiple exposures to FIX concentrates. A nonsense mutation in FIX gene (p.Arg298Stop) was also related to an anaphylactic reaction as reported by Cugno et al 13 In our patient, the gene mutation that caused his disease is a splice mutation at the exon 2 (intron 2), c.252+G>A. The splice genetic mutation can insert, delete or change a number of nucleotides in the specific site when the molecular splicing occurs and the precursor mRNA changes in mature mRNA.…”

supporting

confidence: 80%

The sudden and unexpected appearance of inhibitors in a previously treated severe haemophilia B patient after the switch to albutrepenonacog alpha

2018

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supporting

confidence: 80%

The sudden and unexpected appearance of inhibitors in a previously treated severe haemophilia B patient after the switch to albutrepenonacog alpha

2018

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“…The presence of IgE functionally active on peripheral blood basophils and involved in the hypersensitivity reaction has also been demonstrated by Cugno et al 47 The authors propose a cellular antigen stimulation test (CAST) as a screening tool to identify HB subjects who are prone to hypersensitivity reaction.…”

Section: Risk Factors and Pathophysiologymentioning

confidence: 87%

Inhibitors in Hemophilia B

Quintavalle

Castaman

Baldacci

et al. 2018

Semin Thromb Hemost

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Hemophilia B (HB) is an X-linked bleeding disorder caused by deficiency of factor IX (FIX). Patients with the severe form (FIX <1%) account approximately for 30 to 45% of persons with HB and usually suffer from recurrent joint, soft-tissue, and muscle bleeds. The availability of safe plasma-derived and recombinant products has virtually abolished the risk of viral infections and the adoption of prophylactic regimens has attenuated the impact of hemophilic arthropathy. Therefore, the development of an inhibitor against FIX is currently the most serious complication that can still occur in the new generations of HB patients. The development of an inhibitor in HB is a rare event (1.5-3% of all patients) but is associated with a significant morbidity, related not only to the bleeding risk but also to the frequent occurrence of allergic/anaphylactic reactions and nephrotic syndrome. Due to the relative rarity of this event, few data exist about risk factors, pathophysiology, and clinical aspects of inhibitors in HB. The induction of immune tolerance is often unsuccessful and can be otherwise affected by many complications in patients with history of allergy or anaphylaxis. Therefore, alternative therapeutic strategies and new approaches are developing. The aim of this narrative review is to discuss current knowledge about risk factors, pathophysiology, and clinical aspects of this rare but serious complication.

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“…Патофизиология этих редких ал лергических и анафилактических реакций, связанных с фактором VIII, до конца не изучена. В целом, по мне нию большинства исследователей, наиболее распро страненными реакциями на лекарственные средства и препараты крови являются признаки гиперчувстви тельности 1го типа, опосредованные появлением специфических IgE к фактору VIII [13].…”

Section: результаты и обсуждениеunclassified

A rare case of an anaphylactic reaction to plasma and recombinant blood coagulation factor VIII in a child with severe hemophilia A

2022

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Представлен редкий случай анафилактического шока на введение лекарственного средства, содержащего рекомбинантный фактор свертывания крови VIII 4-го поколения. Анафилактический шок представляет серьезную опасность для жизни пациента с гемофилией А. Временное воздержание от повторного введения фактора свертывания VIII, кожная проба, подтверждающая возможность выбора лекарственного средства, и процедура десенсибилизации пациента предоставляют врачу шанс продолжения заместительной гемостатической терапии у пациента с гемофилией А. Основная цель наблюдения заключается в определении порядка действий по преодолению последствий анафилактического шока и продолжения профилактического введения концентрата фактора свертывания крови VIII для предупреждения кровотечений у ребенка с редким случайным сочетанием анафилактической реакции и врожденных нарушений свертывания крови.Ключевые слова: дети, тяжелая форма гемофилии А, заместительная гемостатическая терапия, анафилактическая реакция, патологический ингибитор свертывания Для цитирования: Дмитриев В. В., Наумович М. Г., Дмитриев Е. В. Редкий случай анафилактической реакции на введение плазменного и рекомбинантного фактора свертывания крови VIII у ребенка с тяжелой формой гемофилии А.

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Involvement of the IgE‐basophil system and mild complement activation in haemophilia B with anti‐factor IX neutralizing antibodies and anaphylaxis

Abstract: In the patient with haemophilia B who experienced anaphylaxis after FIX, but not in the patients with haemophilia B who tolerated FIX, the CAST assay showed FIX-induced LTC4 release, which was associated with high plasma levels of specific anti-FIX IgE and IgG antibodies.

Cited by 9 publications

References 14 publications

The sudden and unexpected appearance of inhibitors in a previously treated severe haemophilia B patient after the switch to albutrepenonacog alpha

The sudden and unexpected appearance of inhibitors in a previously treated severe haemophilia B patient after the switch to albutrepenonacog alpha

Inhibitors in Hemophilia B

A rare case of an anaphylactic reaction to plasma and recombinant blood coagulation factor VIII in a child with severe hemophilia A

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