Intensive Treatment With Recombinant Factor VIIa (NovoSeven^®) To Prevent Joint Bleeding In 4 Patients With Haemophilia A With Inhibitors Undergoing a Regular Program Of Physical Therapy

The development of anti-factor VIII inhibitors is the main complication of modern therapy of hemophilia A (HA) occurring in 25%-30% of severe forms. Inhibitors affect the possibility of a primary prophylaxis and regular physiotherapy, which is an important therapeutic tool to preserve joint function. In patients with severe HA with inhibitors, a prospective randomized study (Konkle et al J Thromb Haemost 5:1904, 2007) and the PRO-PACT retrospective multicenter observational study of a large case series (Young et al Thromb Res 130:864, 2012) have demonstrated the feasibility and effectiveness of secondary prophylaxis with recombinant activated factor VII (rFVIIa, NovoSeven^®) in reducing hemarthrosis.

Aim of the study: This study describes the unique experience of Hemophilia Pediatric Center of Turin (Italy) in a case series of 4 children with severe hemophilia A, history of high-titer inhibitor and mild or severe artropathy, who underwent to regular rehabilitation programme despite presence of inhibitors.

Postural evaluation and gait analysis have been performed for each patient to assess posture and gait performance and plan a tailored therapeutic-rehabilitative treatment.

Each physiotherapy session lasted about 45 minutes. rFVIIa at a dose of 90-180 mcg/kg in a preparation for rehabilitative treatment was administered immediately prior to each session.

During physiotherapy sessions, children carried out both active and passive rehabilitation exercises to maintain adequate muscle strength and preserve joint range of movement (ROM). Basal and final joints angles (in degree) were measured with a goniometer. Manual Muscle Testing (MMT) was applied for grading muscle strength.

Clinical characteristics and individual physiotherapy program are listed below:

A 10-years-old African child with 2 target joints (knees) and 1 bleeding episode/month, has performed 102 sessions of active and passive rehabilitation treatment (November 2010 to November 2012) while on immune tolerance therapy (ITI).

A 12-years-old Caucasian child with 3 target joints (left elbow, knees) has performed a total of 16 sessions (February 2011 to April 2011).

A 2-years-old Caucasian child with a target joint (knee) has performed a total of 20 sessions (February 2011 to August 2012) while on ITI.

A 8-years-old Caucasian child with 4 target joint (elbow, 2 ankles) has performed a total of 149 sessions (November 2009 to November 2012) after failed ITI.

Within 72 hours after each session, no joint nor muscle bleeding have been observed as evidence of the potential role of rFVIIa in preventing bleeding.

The 4 children had a total of 287 physiotherapy sessions, each of them preceded by a single administration of rFVIIa. Treatment provided adequate hemostasis in all patients; no bleeding was observed during the sessions and in the following 3 days. The rehabilitative program obtained a gain of ROM in most of the 9 joints assessed and an improvement in muscle strength was also observed, as described in table. Postural evaluation and gait analysis confirmed these results. We did not observe thrombotic events nor infectious episodes.

Combination of rFVIIa and physiotherapy improved joint ROM and muscle strength in hemophilic children with inhibitors. The rehabilitation program has not given rise to safety issues in these young patients.

Messina:Pfizer: Membership on an entity’s Board of Directors or advisory committees; CSL Behring: Membership on an entity’s Board of Directors or advisory committees; Novo Nordisk: Membership on an entity’s Board of Directors or advisory committees; Baxter: Honoraria; Bayer: Honoraria. Forneris:Novo Nordisk: Honoraria, the autor has received reimbursement for attending a symposium and fees for speaking by Novo Nordisk Other. Off Label Use: rFVIIa is not licensed for nonsurgical prophylaxis in Italy. The use of rFVIIa in prophylaxis as a preparation for physiotherapy treatment currently is considered off label in Italy.