Application of systems biology to identify pharmacological mechanisms of thrombotic microangiopathy evoked by combined activated prothrombin complex concentrate and emicizumab.

ABSTRACT: Emicizumab is a bispecific monoclonal antibody that substitutes for the function of missing or deficient factor VIII (FVIII) in people with hemophilia A (PwHA). Long-term safety and efficacy of emicizumab have been demonstrated in several clinical trials. Nevertheless, in the first of these, three cases of thrombotic microangiopathy (TMA) occurred in PwHA treated with emicizumab receiving high doses of activated prothrombin complex concentrate (aPCC), a bypassing agent used for treating breakthrough bleeds when FVIII neutralizing antibodies (inhibitors) make FVIII replacement ineffective. The aim of the present work is to offer a method to elucidate the pathophysiological and pharmacological mechanisms involved in this treatment-induced TMA. Systems biology and machine learning-based Thera

SUBMITTER: Valls R 

PROVIDER: S-EPMC10284911 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature