الفهرس 
IntroductionOnly 14 pages are availabe for public view
Abstract
SUMMARYUMMARY UMMARY
he benefit of pharmacokinetics (PK) -guided dosing is that both prophylactic and ―on demand‖ dosing will be based on actual FVIII trough and peak levels instead of current FVIII estimates based on body weight and in-vivo recovery based dosing. Knowledge will increase with regards the relationship between FVIII level and bleeding in individual patients.
This study aimed to assess the trough and peak level of factor VIII in patients with hemophilia A on low dose prophylaxis and its impact on the clinical and radiological joint status.
This cross sectional study was performed in Ain-Shams University, Pediatrics Hospital, Hemophilia Clinic. It included 25 children and adolescents with hemophilia A on prophylactic factor VIII during the period from September 2018 to August 2019. Factor VIII used was recombinant 3rd generation with a dose of 45 IU/Kg/week rounded to the nearest 500IU. Trough level of factor VIII was done before prophylactic dose and peak level was done one hour post-infusion through chromogenic assay using STAGO-Immuno-Def VIII reagent. Clinical joint score and Functional Independence Score of Hemophilia (FISH) were done. Radiological joint scores were done using conventional x-ray, ultrasound and MRI. Cut-off level of trough levels was studied at 1% and 1%-5% of factor VIII.
T
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The study included 25 patients, their ages ranged between 3.5-18 years with mean age 11.66 ± 3.72 years. 84% of patients were school students most of them in primary school 44%, 16% of patients are workers. Median trough level was 1 with range 0.69-27; peak level median was 49 with range 19-294. Mean dose of factor VIII was 23.48 ± 7.07 with range 15-45.
Patients were classified into 3 groups,4 patients (21.1%) had trough level <1%, 13 patients (68.4%) had trough level between 1%-5%, 2 patients (10.5%) had trough level > 5%. No significant difference between trough level of factor VIII and clinical joint scores and FISH scores of patients. Median score of the worst joint of patients with trough level >5% was 5 in comparison to 8 and 7 in patients with trough level 1%-5% and <1% respectively. Mean FISH of patients with trough level >5% was 9.50 ± 2.12 in comparison to 12.92 ± 5.41 and 11.00 ± 3.56 for patients with troughs 1%-5% and <1% that was respectively. Comparison between groups with different trough level of factor VIII according to X-ray scores of patients showed no significant difference
Factor VIII trough levels were not correlated with prophylactic doses showing the difference in pharmacokinetics between patients. Dose of prophylactic therapy is not the sole determinant of the trough level of each patient.
Our study revealed 46.7% of patients with trough level of factor VIII >1% were admitted in the hospital during the last 3 months with a median annual bleeding rate of 8, in comparison
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to patients with trough level < 1% where 75% of them were admitted during last 3 months with a median annual bleeding rate of 8.5 while none of patients with trough level of factor VIII >5% was admitted in the hospital during the last 3 months with a median annual bleeding rate of 4, in comparison to patients with trough level 1%-5% where 53.8% of them were admitted during last 3 months for at least once 23.1% with a median annual bleeding rate of 10, and in comparison to patients with trough level < 1% where 75% of them were admitted during last 3 months with a median annual bleeding rate of 8.5. Although non-significant relation but notice that patients with trough level >5% has the lowest annual bleeding rate mean.
Median of the worst individual joint score of patients with trough level ≥ 1% was 8 more than patients with trough level <1% whose median was 7 with mean FISH of 12.47 ± 5.18 more than mean of patients with trough level <1% that was 11.00 ± 3.56, the median of the worst individual joint score of patients with trough level >5% was 5 with mean FISH of 9.50 ± 2.12, thus, maintaining factor VIII trough level > 5% maybe of value for clinical joint outcome even with the non-significant relation.
Assessment of radiological outcomes according to different trough levels in the current study showed the mean score of x-ray of patients with trough factor VIII level ≥ 1% was 7.14 ± 3.28 higher than patients trough level <1% with
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mean score 4.33 ± 3.79, and patients with trough level >5% was 3.00 and median score of MRI and ultrasound of patients with trough >5 was better than other groups, thus, even with the non-significant relation, maintaining trough factor VIII level >5 may be of value in improvement of radiological outcomes for hemophilia patients.
Low trough levels alone did not warrant intensification of the prophylaxis regimen; rather, the dose and dosing frequency should be adjusted based on individual‘s bleeding pattern. In patients with secondary prophylaxis after established joint damage, inconclusive impact of factor VIII levels on joint score levels are found
This could explain the reason for that the group of patients with trough level 1%-5% have the worst clinical joint score, annual bleeding rate mean, radiological assessment scores