Background: Bleeding frequency is an important outcome commonly used in hemophilia studies. There is variation in practice in how bleeding is measured and defined. We therefore performed a systematic review of the studies reporting bleeding frequency in hemophilia patients.

Methods: MEDLINE, EMBASE, and the Cochrane Central Register of Control Trials were searched from January 1990 to January 2014. We included all published studies that included patients with hemophilia A and/or B and reported some measure of bleeding. Two reviewers independently performed title and abstract screening, full-text review and data abstraction of the identified studies.

Results: A total of 118 studies fulfilled the inclusion criteria. Study designs were randomized controlled trials [RCT] (16/118: 14%), cohort (80/118: 68%), cross-sectional (6/118: 5%) and others design (13/118: 11%). The median duration of follow-up (first quartile [Q1], third quartile [Q3]) was 20 (7.9, 50) months. Joint bleeding is the most common site of reported bleeding (66.9%). We found 10 different bleeding outcomes reported (absolute number of bleeding 60 (50.8%) studies, annualized bleeding rate 60 (50.8%) studies, bleed per month 10 (8.5%) studies and others (bleed per patient-year, bleed per week, bleed per season, etc.) 11 (9.3%) studies). Of these, 32 studies (27%) reported only mean or median without dispersion and 33 (28%) studies did not report any measures of central tendency (dispersion).

Conclusions: There is substantial variation in definitions and measures of bleeding outcomes in the hemophilia literature. This creates difficulty and limitations in comparing the outcomes between studies and in performing meta-analysis. The hemophilia research community needs to develop a consensus definition of bleeding and how to address the limitations associated with variations in measures of bleeding between centers and studies.

Table 1.

Measures of bleeding frequency used in the studies

Bleeding outcome measuresn , (%)
1. Bleeding frequency#  
Absolute number of bleeds 60 (50.8) 
Annualized bleeding rate 60 (50.8) 
Bleed per month 10 (8.5) 
Bleed per 100 days 4 (3.4) 
Others (bleed per patient-year, bleed per week, bleed per 5 years, etc.) 11 (9.3) 
2. Central tendency and dispersion#  
Mean with standard deviation 33 (28.0) 
Median with range or interquartile range 35 (27.0) 
Only mean or median 32 (27.1) 
Not reported 33 (28.0) 
Bleeding outcome measuresn , (%)
1. Bleeding frequency#  
Absolute number of bleeds 60 (50.8) 
Annualized bleeding rate 60 (50.8) 
Bleed per month 10 (8.5) 
Bleed per 100 days 4 (3.4) 
Others (bleed per patient-year, bleed per week, bleed per 5 years, etc.) 11 (9.3) 
2. Central tendency and dispersion#  
Mean with standard deviation 33 (28.0) 
Median with range or interquartile range 35 (27.0) 
Only mean or median 32 (27.1) 
Not reported 33 (28.0) 
View Large

#Studies could include more than one level of characteristics.

Disclosures

No relevant conflicts of interest to declare.

Topics:
hemophilia a, hemorrhage, outcome measures, bleeding rate, follow-up, hemarthrosis, screening, embase, medline

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2014 by The American Society of Hematology
2014
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