Hemophilia A
Conditions
Brief summary
Patients with severe hemophilia and inhibitors can be treated effectively by Activated Prothrombin Complex Concentrates (APCC, eg. FEIBA) or High dose recombinant factor VIIa (rFVIIa). Rarely, such patients develop refractoriness to these products for whom therapy with sequential FEIBA and rFVIIa has been recently suggested. The impetus for the present report was a hemophilia A patient with high titer inhibitor (1300BU) who had life threatening hematuria that was resistant to repeated doses of 400µg/kg rFVIIa up to a cumulative dose of 1200 µg/kg given over 6-9 hours. Thrombin generation (TG) tested in vitro was consistent with resistance to high concentrations of rFVIIa but yielded good response to combinations of low doses of rFVIIa+FEIBA. In a desperate attempt to control the bleeding, concomitant therapy of 25 U/kg FEIBA and 40µg/kg rFVIIa was infused and resulted in arrest of bleeding within minutes. Over a span of about one year the patient has been successfully treated by this combination for more than 200 bleeding episodes in muscles and joints.
Detailed description
Inhibitor patients with HR inhibitors were eligible for study enrollment. After consent blood was drawn and ex- vivo spiked with rFVIIa/FEIBA and combinations, assayed by thrombin generation tests. The combination yielding sufficient hemostasis was depicted for patients' therapy of future bleeding episodes. Following actual therapy hemostasis and safety parameters were monitored.
Interventions
DRUGrFVIIa-FEIBA therapy for hemophilia A inhibitors
DOses tailored per ex vivo spiking thrombin generation
DRUGFEIBA- Activated Prothrombin Complexes
Sponsors
Sheba Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
16 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Hemophilia patients with inhibitors * Patients signing informed consent
Exclusion criteria
* Patients under 16 or above 65 * Patients with allergic reaction or adverse events in previous use the concentrates * Patients with high risk of thrombosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hemostasis achieved post therapy | 6-24 hours | Following acute bleeding therapy hemostasis was defined as good, partial or non-satisfactory |
| Safety | 0-24 HOURS | Following therapy presence of any adverse events, especially thromboembolic complications was assessed |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Hemostasis | 0-24 HOURS | Following therapy patients documented time to GOOD response |
Other
| Measure | Time frame | Description |
|---|---|---|
| Coagulation Studies | 0-24 HOURS | cbc fibrinogen and D-dimer were assessed pre and post therapy, thrombin generation was assayed when possible after 1-2 hours |
Outcome results
None listed