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.