title: Mortality caused by intracranial bleeding in non-severe hemophilia A patients.
abstract: Essentials Data on bleeding-related causes of death in non-severe hemophilia A (HA) patients are scarce. Such data may provide new insights into areas of care that can be improved. Non-severe HA patients have an increased risk of dying from intracranial bleeding. This demonstrates the need for specialized care for non-severe HA patients.
  
  
  
  Background Non-severe hemophilia (factor VIII concentration [FVIII:C] of 2-40 IU dL-1) is characterized by a milder bleeding phenotype than severe hemophilia A. However, some patients with non-severe hemophilia A suffer from severe bleeding complications that may result in death. Data on bleeding-related causes of death, such as fatal intracranial bleeding, in non-severe patients are scarce. Such data may provide new insights into areas of care that can be improved. Aims To describe mortality rates, risk factors and comorbidities associated with fatal intracranial bleeding in non-severe hemophilia A patients. Methods We analyzed data from the INSIGHT study, an international cohort study of all non-severe hemophilia A patients treated with FVIII concentrates during the observation period between 1980 and 2010 in 34 participating centers across Europe and Australia. Clinical data and vital status were collected from 2709 patients. We report the standardized mortality rate for patients who suffered from fatal intracranial bleeding, using a general European male population as a control population. Results Twelve per cent of the 148 deceased patients in our cohort of 2709 patients died from intracranial bleeding. The mortality rate between 1996 and 2010 for all ages was 3.5-fold higher than that in the general population (95% confidence interval [CI] 2.0-5.8). Patients who died from intracranial bleeding mostly presented with mild hemophilia without clear comorbidities. Conclusion Non-severe hemophilia A patients have an increased risk of dying from intracranial bleeding in comparison with the general population. This demonstrates the need for specialized care for non-severe hemophilia A patients.
authors.affiliation: Pediatric Hematology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: J I
authors.initials: JI
authors.lastname: Loomans
authors.affiliation: Pediatric Hematology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: C L
authors.initials: CL
authors.lastname: Eckhardt
authors.affiliation: Department of Medicine I, Medizinische Universität Wien, Vienna, Austria.
authors.forename: S E
authors.initials: SE
authors.lastname: Reitter-Pfoertner
authors.affiliation: Karolinska University Hospital, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Holmström
authors.affiliation: Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
authors.forename: B Laros
authors.initials: BL
authors.lastname: van Gorkom
authors.affiliation: Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: F W G
authors.initials: FWG
authors.lastname: Leebeek
authors.affiliation: Sapienza University of Rome, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Santoro
authors.affiliation: University Hospital la Fe, Valencia, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Haya
authors.affiliation: Hematology Department, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Meijer
authors.affiliation: Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
authors.forename: M R
authors.initials: MR
authors.lastname: Nijziel
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: J G
authors.initials: JG
authors.lastname: van der Bom
authors.affiliation: Pediatric Hematology, Academic Medical Center, Amsterdam, the Netherlands.|Department of Plasma Proteins, Sanquin Research, Amsterdam, the Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Fijnvandraat
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D015897:Comorbidity; D005060:Europe; D005169:Factor VIII / Q000627:therapeutic use; D006467:Hemophilia A / Q000150:complications / Q000188:drug therapy / Q000401:mortality*; D006470:Hemorrhage / Q000188:drug therapy; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007391:International Cooperation; D020300:Intracranial Hemorrhages / Q000150:complications / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011994:Recombinant Proteins / Q000627:therapeutic use; D012307:Risk Factors; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; C078147:F8 protein, human; D005169:Factor VIII
keywords: cohort study; epidemiology; hemophilia A; intracranial hemorrhage; mortality