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High-responding Inhibitor (high-responding + inhibitor)

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Medical Sciences	100%

Selected Abstracts

Immune tolerance induction with high von Willebrand factor/factor VIII content ratio concentrate in children with haemophilia A and high-responding inhibitor

HAEMOPHILIA, Issue 2 2009
H. PLATOKOUKI
No abstract is available for this article. [source]

Continuous infusion of factor concentrates in children with haemophilia A in comparison with bolus injections

HAEMOPHILIA, Issue 3 2006
C. BIDLINGMAIER
Summary., Although the concept of continuous infusion (CI) of factor concentrates is well known, prospective paediatric data are rare. We present a prospective open-labelled non-randomized study focusing on safety, efficacy and factor VIII (FVIII) usage compared with bolus injections (BI) in children. In 43 consecutive patients (0.5,17 years; median: 9.6) undergoing different operations, CI was started with an initial FVIII-bolus of 70 IU kg,1 bodyweight, followed by a median infusion rate of 4.4 IU kg,1 h,1 (range: 2.8,9.5) dose adjusted for daily FVIII levels (target: 60,80%). No direct serious adverse events occurred; however, two out of 43 patients, both from the group of four patients with less than 20 exposure days (ED) before starting CI, developed a high-responding inhibitor. Two CI patients showed mild thrombophlebitis or rash. Infusion rates needed to achieve adequate FVIII levels were highly predictable and could be reduced because of decreasing FVIII clearance. Bleeding, requiring additional boli, was observed in eight out of 43 patients. Therapy duration and factor usage of CI were influenced by the procedure, but not by the product used or thrombophilia. Twelve of these CI patients were compared with 12 contemporary consecutive age- and procedure-matched BI patients. Compared with BI patients, CI patients saved 30% FVIII (812.9 vs. 563.2 IU kg,1, P < 0.006). We conclude that CI forms a safe and effective method for perioperative care in children and reduces factor usage. Because of the unknown risk of inhibitor development, we will use CI only in patients beyond 20 ED. [source]

Factor VIII gene (F8) mutations as predictors of outcome in immune tolerance induction of hemophilia A patients with high-responding inhibitors

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 11 2009
A. COPPOLA
Summary.,Background:, Immune tolerance induction (ITI) is the only therapeutic approach that can eradicate factor VIII (FVIII) inhibitors in patients with hemophilia A. Predictors of ITI outcome are still debated, and the role of F8 gene mutations in this is not well established. Objectives: To investigate the relationship between F8 genotype and ITI outcome in patients with severe hemophilia A and high-responding inhibitors. Patients and Methods:F8 mutations were identified in 86 patients recruited as part of the Italian ITI registry (the PROFIT study). ITI outcome was centrally reviewed according to the following definitions: success (undetectable inhibitor and normal FVIII pharmacokinetics), partial success (inhibitor titer < 5 BU mL,1 and/or abnormal FVIII pharmacokinetics), and failure. Results:F8 mutations known to be associated with a high risk of inhibitor development (large deletions, inversions, nonsense mutations and splice site mutations) were found in 70 patients (81%); among these, the intron 22 inversion was present in 49 patients (57%). In 16 patients (19%) lower-risk F8 defects (small insertions/deletions and missense mutations) were identified. The latter group of patients showed a significantly higher ITI success rate than those carrying high-risk mutations [13/16 (81%) vs. 33/70 (47%); risk ratio 1.7, 95% confidence interval (CI) 1.1,2.1, P = 0.01]. On multivariate analysis, the mutation risk class remained a significant predictor of success [adjusted odds ratio (OR) 6.2, 95% CI 1.1,36.0, P = 0.04], as were inhibitor titer at ITI start (< 5 BU mL,1, OR 11.8, 95% CI 3.5,40.2, P < 0.001), and peak titer during ITI (< 100 BU mL,1, OR 11.4, 95% CI 3.2,40.8, P < 0.001). Conclusions: ITI success is influenced by F8 genotype. This knowledge should contribute to the stratification of prognosis, and to the clinical choices made for ITI in patients with high-responding inhibitors. [source]