Long-Term Experience with FEIBA Prophylaxis for Hemophilia Patients with High Responder Inhibitors: Izmir Experience
Authors: Kavakli Kaan , Balkan Can , Yilmaz Karapinar Deniz , Karadas Nihal Ozdemir , Onder Sivis Zuhal , Deveci Burcu , Sahin Akkiz 
Published: October 2019

Abstract
Activated prothrombin complex concentrates (aPCC) (FEIBA, Baxter) is one of the key treatment options for stopping acute bleeds and also recently have been reported for secondary prophylaxis with the aim of bleeding reduction and maintain joint functions in patients with high responder (HR) inhibitors.
In our country, aPCC prophylaxis is on-label treatment and able to re-imbursed with some limitations. In this study, we have collected retrospective data related aPCC prophylaxis regimens in patients with HR inhibitors for last 6 years of period. In our center, we had totally 16 patients with HR inhibitors and severe hemophilia-A (FVIII <1%). Five of them (1/3) did not proceed to prophylaxis due to relatively low bleeding rate. However, in eleven patients (2/3) aged one to thirty years (mean age 11.8±9.7), we have initiated long-term aPCC prophylaxis for bleeding reduction. In respect of ageing we had three sub-groups as toddlers (n=3), boys (n=4) and young adults (aged; 17-18-25-30)(n=4). Inhibitor titers range was 5.7 to 400 BU/ml (mean 84 BU) at the beginning. Eight patients had already target joints (1 to 3) prior to prophylaxis and all patients had arthropathies except two new diagnosed babies. Any patient in concurrent immun tolerance induction regimen. Dose was ranged from 25 to 100 IU/kg according to re-imbursment regulations. For four young adult patients dose was able to used as 25 IU/kg, for infants it was 100 IU/kg. Frequency of infusions were administered as twice weekly period except three patients. Median treatment duration was 2 years (range; 6 mo to 5 years). Radioisotope synovectomy sessions were needed in four young adult patients for local adjustment treatment of target joints together with continuation of FEIBA prophylaxis. All infusions were done in home setting except for babies.
Compliance to regimen was generally good however four young adult patients gave a pause for one to three months due to psyco-social reasons. Two infants had periphereal vein problems and inserted a port-a-cath however it withdrawed due to infection. In all patients, hematomas and bleedings in joints significantly decreased with different rates. Annual bleeding rate was 3.5±2.4 whereas prior to prophylaxis it was 9.0±5.3. Bleeding episodes were decreased as average a 60% reduction during aPCC prophylaxis. This reduction rate also obtained also in four young adults even though using relatively lower doses (25 IU/kg twice weekly). However radioisotope synovectomy was also used for target joints of these patients and probably gained additional effect. Orthopedic status was generally maintained in most of patients and improved in six patients. Target joint availability and synovitis in physical examination was disappeared in five patients. No safety concerns observed. Any thrombotic problem was recorded. Anamnestic reaction to aPCC was not observed in any patient. Inhibitor titers were decresead in all patients during prophylaxis regimen. Interestingly, inhibitor activity was disappeared in three patients however recovery rates of them were not satisfactory and aPCC prophylaxis continued despite of inhibitor negativity.
This six years of observation reflects that aPCC prophylaxis can be used safely and effectively to reduce bleeding episodes and to maintain and/or improve orthopedical status in most patients. This procedure may be effective even in lower doses as 25 IU/kg with twice weekly period and may be recommended for developing countries for bleeding reduction.

Disclosures
Kavakli: Baxter: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.