Related Experiment Videos
Postoperative use of rFVIIa by continuous infusion in a haemophilic boy
J I Lorenzo1, J M Montoro, J A Aznar
1Unidad de Coagulopatías Congénitas, Hospital 'La Fe', Valencia, Spain. jlorenzoh@aehh.org
Insights
Continuous infusion of recombinant factor VIIa (rFVIIa) proved safe and effective for managing postoperative bleeding in a hemophilic patient with an inhibitor. This method offers potential cost-effectiveness for expensive factor concentrates.
Area of Science:
- Hematology
- Pharmacology
Background:
- Continuous infusion of coagulation factor concentrates is established as safe and effective.
- Recombinant factor VIIa (rFVIIa) is costly, necessitating exploration of cost-effective delivery methods like continuous infusion.
Observation:
- A hemophilic boy with a high-titer FVIII inhibitor experienced worsening hemarthrosis despite intermittent rFVIIa boluses.
- Continuous infusion of rFVIIa (20 microg kg(-1) h(-1)) was initiated postoperatively, maintaining plasma levels between 6.3 and 10.4 IU mL(-1).
- Precipitates containing FVIIa formed in syringes when low molecular weight heparin was added to rFVIIa concentrates.
Findings:
- Continuous rFVIIa infusion at 6-10 IU mL(-1) plasma levels was safe and effective in preventing postoperative hemorrhage.
- The addition of heparin to rFVIIa concentrates may lead to precipitation and should be avoided.
- Individual pharmacokinetic evaluation is crucial for optimizing rFVIIa dosing, particularly in pediatric patients.
Implications:
- Continuous infusion of rFVIIa presents a viable and potentially cost-effective strategy for managing bleeding in hemophilia patients with inhibitors.
- Careful consideration of co-administered substances, like heparin, is necessary to prevent drug-related complications.
- Personalized pharmacokinetic assessments can guide precise rFVIIa dosing for improved therapeutic outcomes.
Abstract:
Continuous infusion of coagulation factor concentrates has proved to be safe and effective. Because rFVIIa (NovoSeven is a very expensive product and very frequent doses are needed, continuous infusion is expected to be highly cost-effective. The postoperative use of continuous infusion of rFVIIa in a haemophilic boy with a high titre FVIII inhibitor is reported. He presented with a large right knee haemarthrosis and was treated with intermittent doses of rFVIIa. After a transient improvement the haemarthrosis became worse and an open evacuation of the joint had to be made under treatment with bolus injections of rFVIIa for 3 days (120 microg kg(-1) every 2 h). A previous pharmacokinetic evaluation in this patient had showed that FVIIa recovery and half-life were less than expected. Continuous infusion of rFVIIa (20 microg kg(-1) h(-1)), with added low molecular heparin to prevent local thrombophlebitis, was started on the fourth postoperative day and maintained unchanged for 7 days. Four additional single bolus injections were given for early joint mobilization. The intervals between replacements of the pump syringes were progressively increased from 6 to 12 h and then up to 24 h. FVIIa plasma levels during continuous infusion ranged between 6.3 and 10.4 IU mL(-1). Although +FVIIa assays seemed to show good stability, we observed the formation of precipitates inside the syringes. The precipitates seemed to contain FVIIa. We concluded that FVIIa+ plasma levels of 6-10 IU mL(-1) were safe and effective to prevent postoperative haemorrhage in this patient. The addition of heparin to the rFVIIa concentrates, however, may cause precipitation and should be avoided. Individual pharmacokinetic evaluation may be useful to select the appropriate initial doses, especially in young patients.