This protocol covers a specific and clinically challenging sub-population: patients with severe hemophilia A who have developed high-responding factor VIII (FVIII) inhibitors — defined as a titer greater than 5.0 Bethesda units — and who are initiating immune tolerance induction (ITI).
Clinical scenario: Severe hemophilia A with high-responding FVIII inhibitors (titer >5.0 BU) at the point of starting immune tolerance induction. A high-responding inhibitor is defined as >5.0 Bethesda units, distinguishing this population from low-responding inhibitor cases (≤5.0 BU).
Approach: The ISTH Hemophilia Guideline Panel recommends immune tolerance induction using FVIII concentrate for this population. Two dosing strategies are defined in the full protocol — the choice between them, the supporting evidence grading, and the full clinical decision framework are available in the complete regimen.
DOI: 10.1016/j.jtha.2024.05.026
In individuals with severe hemophilia A with high-responding inhibitors who will start immune tolerance induction, the ISTH Hemophilia Guideline Panel suggests immune tolerance induction with either low- or high-dose FVIII concentrates (conditional recommendation, based on very low–certainty evidence ⨁◯◯◯).
A low-responding and a high-responding inhibitor are defined as an inhibitor ≤ 5.0 BU and >5.0 BU, respectively.
For this recommendation, a high-dose regimen refers to 200 IU/kg body weight daily and a low-dose regimen refers to 50 IU/kg 3 times per week.
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