High-dose prophylaxis for severe hemophilia A [25–40 factor (F) VIII Units (u) kg−1 on alternate days] reduces arthropathy, but does so at great cost. (

NEJM
2007
;
357
:
535
–544
). Less intensive prophylaxis regimens might be cost-effective while reducing the need for indwelling venous access devices and their attendant complications. Tailored prophylaxis starts with FVIII, 50 u kg−1 weekly (Step1). If bleeding frequency is unacceptable (4 joint/soft tissue bleeds or 5 bleeds into a joint on a step of protocol), or if a target joint develops (≥3 bleeds into a single index joint-ankle, elbow or knee) over a consecutive 3-month period the dose of FVIII is escalated to 30 u kg−1 twice weekly (Step 2); a third escalation to 25 u kg−1 on alternate days if bleeding frequency remains unacceptable (Step3).

Objectives: To assess the degree of joint damage in the 6 index joints for subjects receiving tailored prophylaxis.

Methods: We studied an inception cohort of boys ages 1–2.5 years with severe hemophilia A (<2% FVIII) and no inhibitors treated with tailored prophylaxis. Patients were followed at 6 monthly intervals and parents have kept detailed diaries. Joint damage was measured using a validated physiotherapy joint score and function was assessed using the Child Health Assessment Questionnaire (CHAQ)

Results: 54 boys were enrolled from 11 Canadian hemophilia treatment centers. The total follow-up is 3423 patient months (mean 62.2 months, median 54 months and range 5–117 months). 16 (29.6%) boys have been escalated to Step 2 and 14 (25.9%) have escalated to Step 3. 11 of the escalations were due to target joint bleeding. Subjects on study had a mean of 1.4 joint bleeds/patient-year. Physiotherapy Scores Maximum Possible Score Median Observed Range Ankles 56 2 0–20 Elbows 48 0 0–13 Knees 56 0 0–15 All Joints Swelling 18 0 0–4 Muscle Atrophy 18 0 0–3 CHAQ 3 0 0–2 89% of participants were compliant with the primary prophylaxis protocol. Non compliant subjects had the poorest outcomes. No treatment related adverse events have occurred.

Conclusion: Tailored primary prophylaxis should be considered as a valid option for long term prophylaxis in young boys with severe hemophilia A.

Maximum Possible ScoreMedianObserved Range
Ankles 56 2 0–20 
Elbows 48 0 0–13 
Knees 56 0 0–15 
All Joints  
Swelling 18 0 0–4 
Muscle Atrophy 18 0 0–3 
CHAQ 3 0 0–2 
Maximum Possible ScoreMedianObserved Range
Ankles 56 2 0–20 
Elbows 48 0 0–13 
Knees 56 0 0–15 
All Joints  
Swelling 18 0 0–4 
Muscle Atrophy 18 0 0–3 
CHAQ 3 0 0–2 
View Large

Topics:
hemophilia a, edema, hemorrhage, muscular atrophy, physical therapy, adverse event, follow-up, hemarthrosis, joint disorders, venous access

Author notes

Disclosure:Research Funding: The study was funded by CIHR and Bayer Canada. Honoraria Information: Honourarium for speaking at symposium. Membership Information: Sits on advisory board for Bayer, Baxer and Amgen.

2007, The American Society of Hematology
2007
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