Abstract Number: PB1064
Meeting: ISTH 2020 Congress
Background: Therapy for hemophilia A, or factor VIII (FVIII) deficiency, generally consists of infusions of plasma-derived or recombinant FVIII (pdFVIII and rFVIII). Development of inhibitors renders FVIII infusions ineffective. A rare FVIII complication is development of hypersensitivity reactions, ranging from isolated urticaria to anaphylaxis.
Aims: Develop a management regimen for severe hypersensitivity to FVIII and a high-titer inhibitor.
Methods: This 4-year-old boy was diagnosed at birth with severe FVIII deficiency (< 1% activity). During treatment, he developed a high-titer inhibitor (140 BU). ITI was attempted with ALPHANATE, a pdFVIII, KOGENATE, a second generation rFVIII, and NUWIQ, a fourth generation rFVIII, but he suffered from increasingly severe hypersensitivity reactions to each product.
Results: The patient underwent 8 days of a desensitization protocol to NUWIQ, with a total daily dose of 50 IU/kg (Figure 1). Premedication (methylprednisolone/diphenhydramine) was given on days 1 through 5. ITI was initiated on day 9 with 50 IU/kg/day administered over 10 minutes; this interval was shortened to 5 minutes over the next week. He continued this dose daily until tolerance induction. His FVIII inhibitor titer was 7.2 BU at the start of ITI in 11/2018 and rose to 32 BU before declining to 0.0 BU in 3/2019.
Desensitization to FVIII has been reported in at least 2 cases and consisted of step-wise increases of FVIII infusions over several weeks, with prolonged use of premedication and partial success. In contrast, this patient was desensitized over the course of 8 days with limited premedication, and started ITI on day 9. With an ITI regimen of 50 IU/Kg/day, this patient’s inhibitor titer decreased to undetectable within 4 months.
Conclusions: The FVIII desensitization regimen described appears to offer a practical, cost-effective therapeutic approach to both the management of hypersensitivity as well as the induction of safe and effective immune tolerance.
To cite this abstract in AMA style:Mitchell W. Rapid Desensitization and Subsequent Immune Tolerance Induction in a Patient with Hypersensitivity and Inhibitor to Factor VIII [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/rapid-desensitization-and-subsequent-immune-tolerance-induction-in-a-patient-with-hypersensitivity-and-inhibitor-to-factor-viii/. Accessed December 6, 2021.
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