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Efficacy, safety and pharmacokinetics of a new high‐purity factor X concentrate in women and girls with hereditary factor X deficiency
Author(s) -
Kulkarni R.,
James A. H.,
Norton M.,
Shapiro A.
Publication year - 2018
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.13983
Subject(s) - medicine , pharmacokinetics , factor x , pediatrics , adverse effect , risk factor , thrombin , platelet
Essentials Plasma‐derived factor X concentrate (pdFX) is used to treat hereditary factor X deficiency. pdFX pharmacokinetics, safety and efficacy were assessed in factor X‐deficient women/girls. Treatment success rate was 98%; only 6 adverse events in 2 subjects were possibly pdFX related. On‐demand pdFX 25 IU kg −1 was effective and safe in women/girls with factor X deficiency.Summary Background A high‐purity, plasma‐derived factor X concentrate (pd FX ) has been approved for the treatment of hereditary FX deficiency, an autosomal recessive disorder. Objective To perform post hoc assessments of pd FX pharmacokinetics, safety and efficacy in women and girls with hereditary FX deficiency. Patients/Methods Subjects aged ≥ 12 years with moderate/severe FX deficiency (plasma FX activity of < 5 IU dL −1 ) received on‐demand or preventive pd FX (25 IU kg −1 ) for ≤ 2 years. Results Of 16 enrolled subjects, 10 women and girls (aged 14–58 years [median, 25.5 years]) received 267 pd FX infusions. Mean monthly infusions per subject were higher among women and girls (2.48) than among men and boys (1.62). In women and girls, 132 assessable bleeding episodes (61 heavy menstrual bleeds, 47 joint bleeds, 15 muscle bleeds, and nine other bleeds) were treated with pd FX , with a 98% treatment success rate versus 100% in men and boys. Mean pd FX incremental recovery was similar in the two groups (2.05 IU dL −1 versus 1.91 IU dL −1 per IU kg −1 ), as was the mean half‐life (29.3 h versus 29.5 h). Of 142 adverse events in women and girls, headache was the most common (12 events in six subjects). Six events (two infusion‐site erythema, two fatigue, one back pain, one infusion‐site pain) in two subjects were considered to be possibly pd FX ‐related. Following the trial, pd FX was used to successfully maintain hemostasis in two subjects undergoing obstetric delivery. Conclusions pd FX was well tolerated and effective in women and girls with FX deficiency. Although women and girls had different bleeding symptoms and sites than men and boys, their pd FX pharmacokinetic profile was comparable.