Treatment and prevention of bleeding in congenital hemophilia A patients with inhibitors

• Published in: Transfusion and apheresis science Vol. 57; no. 4; pp. 466 - 471
• Main Author: Teitel, Jerome M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-08-2018
• Subjects: Activated prothrombin concentrate; Alpha 1 antitrypsin; ATIII antagonist; Concizumab; Emicizumab; Factor VIIa - pharmacology; Factor VIIa - therapeutic use; Factor VIII; Factor VIII - antagonists & inhibitors; Factor VIII inhibitor; Health technology assessment; Hemophilia A; Hemophilia A - drug therapy; Hemophilia A - pathology; Hemorrhage - prevention & control; Humans; Inhibitor by passing activity; Novel agents; Recombinant activated factor VII; TFPI antagonists; Emicizumab; TFPI antagonists; Concizumab; Alpha 1 antitrypsin; Activated prothrombin concentrate; Recombinant activated factor VII; Factor VIII; Factor VIII inhibitor; Novel agents; Inhibitor by passing activity; ATIII antagonist; Hemophilia A
• ISSN: 1473-0502; 1878-1683
• DOI: 10.1016/j.transci.2018.07.011

The treatment of bleeding in hemophilia A patients with persistent inhibitory antibodies to factor VIII is problematic. The current standard hemostatic agents for inhibitor patients are recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrate (APCC). These “inhibitor bypassing agents” are less reliably effective than are replacement therapies for patients without inhibitors, and there are no validated laboratory assays to monitor their efficacy. Furthermore, only single rFVIIa and APCC products are available worldwide, and their use can be complicated, albeit rarely, by thrombotic events. For all these reasons, new approaches to treat bleeding in inhibitor patients are eagerly awaited. These new approaches include replacement therapy with porcine factor VIII concentrate (currently approved for use in acquired hemophilia patients), bispecific antibodies to simulate the biologic function of factor VIII (already in use in some jurisdictions), pegylated forms of activated factor VII, and strategies targeting the natural anticoagulants TFPI and antithrombin, which create a hypercoagulable phenotype to counterbalance the hypocoagulability imposed by hemophilia.