Females With FVIII Deficiency Have Reduced Mean Overall Joint Range Of Motion

While hemarthrosis contributes to morbidity in males with Hemophilia, less is known about joint destruction in females with FVIII deficiency. Our hypothesis was that females with FVIII deficiency enrolled in the Universal Data Collection (UDC) project had a reduced mean overall joint range of motion (ROM) compared to historic controls from the Normal Joint Study.

We employed a cross-sectional study design utilizing the UDC dataset. The overall joint ROM was the sum of the right and left ROM measurements of the five joints (hip, ankle, elbow, knee, shoulder) for the females with FVIII deficiency from the UDC and for healthy females without the deficiency 2-69 years of age from the Normal Joint Study. Females that were very obese (BMI >35) were excluded from the Normal Joint Study thus they were excluded from the UDC cohort. Mean overall joint ROM between affected and normal females was assessed for statistical difference using the non-parametric Wilcoxon-rank-sum test. Results were displayed as mean overall ROM with 95% confidence interval (CI) and p-value by age group and factor deficiency. Multivariate linear regression was performed using the General Linear Model (GLM) procedure with the overall joint ROM as the dependent variable and the clinical hemophilia severity as the independent variable adjusting for age, race, body mass index (BMI) and number of joint bleeds reported over the last six months.

A total of 522 females were identified with FVIII deficiency; 28% (144/522) of females were removed because of inability to assign factor deficiency type and 14% (75/522) of females were removed due to being very obese (BMI>35) or outside the age range studied in the Normal Joint Study. Final analysis was performed on 303 females with FVIII deficiency between the ages of 2-69 years for comparison to the control group. As FVIII activity decreased, the mean overall joint range of motion became reduced and in most cases was significantly lower than that of the controls (see table 1). In FVIII deficient females there was a significant (p< 0.0001) correlation between Hemophilia severity and mean overall joint ROM. Furthermore, using multivariate linear regression analysis, stratifying by age and clinical hemophilia severity and controlling for BMI and race, females with severe (<1%), moderate (≥1% and ²5%) and mild (>5% and<40%) deficiency had a significantly reduced mean overall joint ROM compared to normal female controls.

View Large

Females with FVIII deficiency enrolled in the UDC project had reduced mean overall joint ROM compared to normal females without factor deficiency. Mean overall joint ROM was reduced in FVIII deficient females as young as age 9 and in those with no self-reported joint bleeding history. Further investigation of reduced joint ROM as evidence of subclinical joint bleeding in FVIII deficient females is warranted.

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

No relevant conflicts of interest to declare.