Prophylaxis in haemophilia with inhibitors: update from international experience.
An antibody response to therapeutically administered factor VIII (FVIII) can occur in up to 30% of patients with haemophilia, resulting in the production of inhibitors that neutralize FVIII coagulant activity. Immune tolerance induction (ITI) therapy can be used to eradicate inhibitors in these patients, allowing them to continue with factor replacement therapy. Patients with inhibitors (prior to initiation of ITI, while on ITI or those who fail ITI) experience more difficulty in treating bleeds than those patients who do not develop inhibitors. Increasingly, prophylaxis with bypassing therapy is being employed in patients who develop inhibitors. Two bypassing agents, a plasma-derived activated prothrombin complex concentrate [aPCC (FEIBA; Baxter AG, Vienna, Austria)] and NovoSeven [recombinant factor VIIa (rFVIIa); NovoNordisk, Denmark] are potentially available for prophylaxis in patients with haemophilia who have developed inhibitors. Results from recent retrospective studies demonstrate the efficacy and safety of both aPCC and rFVIIa in decreasing the frequency of bleeding episodes in patients with haemophilia and inhibitors. In this article, we highlight a number of ongoing studies that aim to identify patients who should be placed on prophylaxis with bypassing agents.
Division of Hematology/Oncology, Hospital for Sick Children, Toronto, ON, Canada. manuel.carcao@sickkids.on.ca
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D000293:Adolescent; D000328:Adult; D019774:Blood Coagulation Factor Inhibitors / Q000276:immunology; D001779:Blood Coagulation Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005164:Factor IX / Q000008:administration & dosage / Q000627:therapeutic use; D005169:Factor VIII / Q000008:administration & dosage / Q000627:therapeutic use; D015942:Factor VIIa / Q000008:administration & dosage / Q000627:therapeutic use; D006395:Hemarthrosis / Q000517:prevention & control; D006467:Hemophilia A / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007223:Infant; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D055815:Young Adult
D019774:Blood Coagulation Factor Inhibitors; D001779:Blood Coagulation Factors; D011994:Recombinant Proteins; D005169:Factor VIII; D005164:Factor IX; C103587:recombinant FVIIa; D015942:Factor VIIa