Case Presentation:
A newborn male born via uncomplicated vaginal delivery was diagnosed
with severe hemophilia A after being transferred from an outlying
hospital for continued bleeding from heel-stick and circumcision sites.
Laboratory evaluation revealed an elevated activated partial
thromboplastin time (aPTT) of 99.7 seconds (21-32 sec), hemoglobin
concentration of 16.0 g/dL (11.0-14.5 g/dL), and factor VIII activity
<1%. Genetic testing was obtained due to no family history of
hemophilia that showed an F8 gene variant c.5816C>A
(p.Ala1939Glu). He was prescribed recombinant factor VIII (rFVIII)
concentrate (ADVATE, Takeda, Tokyo, Japan) 60 IU/kg on day two of life
as well as red blood cell transfusion for a decreased hemoglobin
concentration of 6.9 g/dL. Bleeding was controlled with further ADVATE
60 IU/kg every 8 hours for 2 days, then every 12 hours for 2 days
without bleeding recurrence.
At six months of age, the patient was prescribed prophylaxis with once
weekly PEGylated rFVIII (ADYNOVATE, Takeda, Tokyo, Japan), due to
requiring multiple on-demand doses for spontaneous and traumatic soft
tissue bleeding. His parents desired to avoid implantation of a CVAD due
to the associated known risks. His mother was successfully trained on
peripheral venous access and infusion of FVIII concentrates. As he
became more mobile, his parents noticed an increase in spontaneous
ecchymosis despite 1-2 times weekly ADYNOVATE prophylaxis and became
concerned for potentially more severe bleeding events. After multiple
discussions regarding treatment options, the parents chose to remain on
FVIII prophylaxis with ALTUVIIIO (Sanofi Pharma, Paris, France) while
avoiding CVAD placement.
At 19-months of age, the patient received his first ~50
IU/kg prophylactic dose of ALTUVIIIO (actual 56 IU/kg, 3 – 220 IU
vials). His weight at the time of initial infusion was 11.9kg. The
ALTUVIIIO package insert recommends infusion rate at no faster than 6
minutes per vial if body weight is <20 kg (Table
2)4. This is reportedly due to 5% sucrose in the
final formulation of ALTUVIIIO, which is in accordance with the maximum
infusion rate for intravenous immunoglobulin (IVIG) containing sucrose
per the European Medicine Agency (EMA) guideance4.
This resulted in a peripheral infusion time of 18 minutes, which was
challenging due to patient age and venous access. The patient’s FVIII
activity was obtained prior to and 30 minutes post infusion using the
same one-stage FVIII activity assay used in the clinical trials (Table
1)⁶. The patient’s parents chose to have subsequent weekly infusions in
the clinic setting due to concern over the long infusion time and
potential for infusion failure and product wastage with home
administration. He tolerated all infusions well with no adverse events.