Application of a hemophilia mortality framework to the Emicizumab Global Safety Database

J Thromb Haemost. 2021 Jan;19 Suppl 1(Suppl 1):32-41. doi: 10.1111/jth.15187.


Background: As the first non-factor replacement therapy for persons with congenital hemophilia A (PwcHA), emicizumab's safety profile is of particular interest to the community.

Objectives: We applied an algorithm for categorization of fatal events contemporaneous to emicizumab using reporter-assessed causality documented in the Roche Emicizumab Global Safety Database.

Patients/methods: All fatalities in PwcHA reported to the database (from clinical trials, pre-market access, and spontaneous post-marketing reports) were categorized into: associated with hemophilia A-hemorrhagic, thrombotic, human immunodeficiency virus (HIV)/hepatitis C virus (HCV), hepatic (non-HCV); associated with general population-trauma/suicide, non-HA-associated conditions; or, unspecified. Reported cause of death was not reassessed.

Results: As of cut-off May 15, 2020, 31 fatalities in PwcHA taking emicizumab were reported. Median age at death was 58 years; 51% had factor VIII inhibitors. Fifteen fatalities were considered associated with HA; overall, the most frequent category was hemorrhage (11/31). Of these, six had a history of life-threatening bleeds, and four had a history of intracranial hemorrhage. The remaining HA-associated fatalities were related to HIV/HCV (3/31) and other hepatic causes (1/31). No cases were categorized as thrombotic. Of 10 cases considered not associated with HA, two were categorized as cardiovascular (non-thrombotic), five as infection/sepsis, and one each of trauma/suicide, pulmonary, and malignancy. Six cases were unspecified.

Conclusions: No unique risk of death was associated with emicizumab prophylaxis in PwcHA. The data reveal that mortality in PwcHA receiving emicizumab was primarily associated with hemorrhage or non-HA-associated conditions, and was not reported by treaters to be related to emicizumab treatment.

Keywords: benchmarking; cause of death; hemophilia A; mortality; safety.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Bispecific / adverse effects*
  • Antibodies, Bispecific / therapeutic use
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Factor VIII
  • Female
  • Hemophilia A / diagnosis
  • Hemophilia A / drug therapy*
  • Hemophilia A / mortality*
  • Humans
  • Life Expectancy
  • Male


  • Antibodies, Bispecific
  • Antibodies, Monoclonal, Humanized
  • emicizumab
  • Factor VIII