Prevention of bleeds in hemophilia patients with inhibitors: Emerging data and clinical direction

Abstract

In patients with hemophilia, the development of high-responding inhibitors to factor VIII prevents adequate replacement therapy and results in increased risk of serious bleeding episodes, poor control of joint bleeding, and progressive, debilitating joint disease. Immune tolerance therapy can eradicate inhibitors, but it is not uniformly successful. Emerging data suggest that prophylaxis using activated prothrombin complex concentrates may be effective and safe in reducing the incidence of joint bleeding during immune tolerance therapy and for patients in whom immune tolerance induction fails. However, only controlled clinical trials will ultimately demonstrate whether prophylaxis can prevent joint bleeding and damage, and improve quality of life in patients with inhibitors. Am.

Successful self‐infusion of activated prothrombin complex concentrate for prophylaxis in a child with a factor VIII inhibitor

“…Consistent with the current case report, two of the previous studies also found decreased inhibitor titers during FEIBA prophylaxis [8,10]. Notably, studies by Escuriola-Ettingshausen et al [9], Valentino and Salit [12], and Leissinger [7] also showed maintenance or improvement of existing arthropathy. In the present patient, effects of FEIBA on arthropathy could not be determined, as he had no joint disease at the start of FEIBA.…”

“…FEIBA also has been used for prophylaxis during immune tolerance induction [6]. Regular prophylactic replacement with PCC or APCC, however, has not been used routinely in inhibitor-positive patients in the United States, as controlled trials of prophylaxis have not been conducted and there is no consensus on standard dosing [7]. There are several reports on the efficacy for prevention of bleeding by PCC or APCC in patients with inhibitors [6,[8][9][10][11][12].…”

Anti-Inhibitor Coagulant Complex Prophylaxis in Hemophilia with Inhibitors

“…1 The development of high-titer factor VIII inhibitors (>5 Bethesda units [BU]) complicates treatment because bleeding no longer responds to standard factor VIII replacement. 2,3 Alternative forms of clottingfactor concentrates, known as bypassing agents, are used to treat bleeding in these patients. 3 Two bypassing agents are currently available: anti-inhibitor coagulant complex (AICC) and recombinant activated factor VII (rFVIIa).…”

“…2,3 Alternative forms of clottingfactor concentrates, known as bypassing agents, are used to treat bleeding in these patients. 3 Two bypassing agents are currently available: anti-inhibitor coagulant complex (AICC) and recombinant activated factor VII (rFVIIa). Both agents control approximately 80% of bleeding episodes in patients with hemophilia and inhibitors.…”

Women leaders in hematology: Inspirations & insights

“…In Dr. DiMichele's own words, "there is too much left to do." [43,44], acquired hemophilia A [45], and other coagulation disorders, such as von Willebrand disease. She has been an active investigator for numerous research studies and Principle Investigator for 2 investigator-initiated, multiinstitutional clinical trials of treatments for individuals with hemophilia A and factor VIII inhibitors: the Rituximab for Inhibitors in Congenital Hemophilia (RICH) study [46] and the ProFEIBA study of anti-inhibitor coagulant complex prophylaxis [44].…”