Successful prophylactic treatment of FEIBA in the prevention of bleeding in patients with severe haemophilia A and high titre of FVIII inhibitor
Abstract
Following the elimination of the risk of transmission of infection with the current FVIII and FIX substitutes, the most frightening complication of hemophilia treatment is the formation of the FVIII / IX inhibitor. FVIII neutralizing inhibitor is formed in approximately 20-30% of patients with severe haemophilia A and 1-5% of patients with haemophilia B.
In approximately 75-80% of patients with haemophilia A, the inhibitor can be permanently removed by immunotolerance (ITI), haemophilia B results are worse. Patients who have failed ITI and have a consistently high inhibitor titer (greater than 5.0 Bethesda units [BU]) can not be treated with conventional FVIII / IX concentrates and are reliant on the treatment of bypassing agents such as recombinant activated coagulation factor VII (rFVIIa), known as NovoSeven, and a mixture of procoagulant factors II, VII, IX and X, anticoagulant protein C, tissue factor inhibitor (TFPI) and small amounts of cofactors FV, FVIII and S protein in balanced amount, known as FEIBA. "Bypassing" is to understand the ability of these drugs to bypass FVIII and FIX in the coagulation cascade and activate FX directly.
Both drugs have been used for many years in the treatment of acute haemorrhage in hemophiliacs with an inhibitor but can also be used in prophylactic treatment. They are effective in approximately 80% of bleeding episodes.
The disadvantage of both of these products is difficult prediction and laboratory control of efficacy. Patients with an inhibitor who can not be treated with FVIII / IX concentrates are mostly on-demand treatment bypassing medications and therefore do not benefit from prophylactic treatment as non-inhibitory patients.
Generally, managing bleeding in inhibitor patients is significantly more difficult than in non-inhibitor patients. As a result, these patients are at risk of developing haemophilic arthropathy, which we do not see otherwise any more today.
The physician's effort is therefore to use bypassing products also for prophylactic treatment. It reduces the number of bleeding in the joints and protects patients from severe bleeding into the limb that is endangered, and life-threatening bleeding such as CNS bleeding.
In addition, it limits the number of missed hours in school or employment, reduces visits to health care facilities, hospitalizations or orthopedic interventions, and improves quality of life.