BACKGROUND: Inhibitors are rare in boys with mild hemophilia A (MHA; factor (F)VIII:C > 5%) but may arise following intense FVIII exposure, e.g. continuous infusion (CI). OBJECTIVES: To determine the impact of intense FVIII exposure in inhibitor formation in MHA at our institution and to compare this with previous reports. PATIENTS AND METHODS: We reviewed FVIII exposure and inhibitor development in boys (ages 0-18 years) with MHA followed at our institution from 1996 to 2001 and conducted a Medline search (1966-2002) on the experience of inhibitor development following intensive/CI exposure to FVIII. RESULTS: We identified 54 boys with MHA. Twenty-nine (54%) had been exposed to FVIII. Seven had received FVIII by CI. Four developed inhibitors; three high titer (at ages 10 years, 16 years and 17 years) and one low titer (at 1 month old). All four had received a CI of recombinant (r) FVIII of at least 6 days within 6 weeks of developing inhibitors. Baseline FVIII levels fell to < 1% in all cases and the three with high-titer inhibitors developed severe bleeding. Immune tolerance therapy (ITT) was attempted in two boys and was successful in one. Our literature search identified 35 cases (only four children) with MHA developing inhibitors following intense FVIII exposure often in the context of surgery. CONCLUSIONS: The incidence of inhibitors in our MHA population was 7.4%. If expressed according to exposure the incidence was significantly higher: 14% (4/29) for any exposure to FVIII and 57% (4/7) for exposure by CI. A prospective study to address whether CI is associated with an increased incidence of inhibitor development in MHA is warranted.
BACKGROUND: Inhibitors are rare in boys with mild hemophilia A (MHA; factor (F)VIII:C > 5%) but may arise following intense FVIII exposure, e.g. continuous infusion (CI). OBJECTIVES: To determine the impact of intense FVIII exposure in inhibitor formation in MHA at our institution and to compare this with previous reports. PATIENTS AND METHODS: We reviewed FVIII exposure and inhibitor development in boys (ages 0-18 years) with MHA followed at our institution from 1996 to 2001 and conducted a Medline search (1966-2002) on the experience of inhibitor development following intensive/CI exposure to FVIII. RESULTS: We identified 54 boys with MHA. Twenty-nine (54%) had been exposed to FVIII. Seven had received FVIII by CI. Four developed inhibitors; three high titer (at ages 10 years, 16 years and 17 years) and one low titer (at 1 month old). All four had received a CI of recombinant (r) FVIII of at least 6 days within 6 weeks of developing inhibitors. Baseline FVIII levels fell to < 1% in all cases and the three with high-titer inhibitors developed severe bleeding. Immune tolerance therapy (ITT) was attempted in two boys and was successful in one. Our literature search identified 35 cases (only four children) with MHA developing inhibitors following intense FVIII exposure often in the context of surgery. CONCLUSIONS: The incidence of inhibitors in our MHA population was 7.4%. If expressed according to exposure the incidence was significantly higher: 14% (4/29) for any exposure to FVIII and 57% (4/7) for exposure by CI. A prospective study to address whether CI is associated with an increased incidence of inhibitor development in MHA is warranted.
Authors: M V Ragni; O Ojeifo; J Feng; J Yan; K A Hill; S S Sommer; M N Trucco; D J Brambilla Journal: Haemophilia Date: 2009-06-26 Impact factor: 4.287