Abstract

Due to a founder affect certain regions of the Canadian province of Newfoundland and Labrador have a very high prevalence of mild Hemophilia A. To accurately plan for future health related needs of these patients, a base-line cross-sectional study of a large cohort segregating a known founder mutation (Val2016Ala) was undertaken.

Characteristics of Study Participants

CharacteristicAffected MalesControl MalesP-Values (Affected vs Control)Carrier FemalesControl FemalesP-Value (Carrier vs Control)
Values are expressed as number, mean*, median(interquartile range)†, or percentage 
Overall N 61(5–76yrs) 44(4–81yrs) 0.883 88(8–88yrs) 65(16–78yrs) 0.935 
Factor VIII* 0.15(0.05) 1.29(0.37) <0.001 0.78(0.31) 1.34(0.41) <0.001 
Hepatitis Bc Antibodies 15.8%(9/57) 0%(0/28) 0.012 0%(0/75) 0%(0/58) 
Hepatitis C Positive 19.7%(12/61) 0%(0/33) 0.001 0%(0/88) 0%(0/65) 
HIV Positive 1.6%(1/61) 0%(0/33) 0.420 0%(0/88) 0%(0/65) 
Diabetes 24.4%(11/45) 6.1%(2/33) 0.031 
BMI†(Adults Only) 30.0(27.0–33.0) 27.0(26.0–30.0) 0.028 29.0(20–57) 28.0(19–46) .446 
CharacteristicAffected MalesControl MalesP-Values (Affected vs Control)Carrier FemalesControl FemalesP-Value (Carrier vs Control)
Values are expressed as number, mean*, median(interquartile range)†, or percentage 
Overall N 61(5–76yrs) 44(4–81yrs) 0.883 88(8–88yrs) 65(16–78yrs) 0.935 
Factor VIII* 0.15(0.05) 1.29(0.37) <0.001 0.78(0.31) 1.34(0.41) <0.001 
Hepatitis Bc Antibodies 15.8%(9/57) 0%(0/28) 0.012 0%(0/75) 0%(0/58) 
Hepatitis C Positive 19.7%(12/61) 0%(0/33) 0.001 0%(0/88) 0%(0/65) 
HIV Positive 1.6%(1/61) 0%(0/33) 0.420 0%(0/88) 0%(0/65) 
Diabetes 24.4%(11/45) 6.1%(2/33) 0.031 
BMI†(Adults Only) 30.0(27.0–33.0) 27.0(26.0–30.0) 0.028 29.0(20–57) 28.0(19–46) .446 

Statistically Significant Difference SF-36 & Colorado PE-05 Mean Scores for Affected and Unaffected Males

Affected MalesAffected MalesAffected MalesUnaffected SiblingsUnaffected SiblingsUnaffected Siblingst-test Difference vs References
DimensionnMeanSDnMeanSDP-Value
P<0.05)* Affected Males(age 23–76 years) Unaffected Siblings(age 20–81 years) 
SF-36 Scores        
General Health Scale 44 58.1 28.7 32 71.4 21.4 0.024* 
Role Emotional 44 89.2 19.9 33 98.0 5.5 0.007* 
Colorado PE-05 Musculoskeletal Scores        
Axial Deformity 47 0.9 1.4 33 0.2 0.8 0.008* 
Range of Motion 47 4.2 2.0 33 2.9 1.8 0.005* 
Gait 47 2.4 3.5 33 0.4 1.4 0.002* 
Left Ankle 47 3.3 5.0 33 1.0 2.9 0.015* 
Right Ankle 47 3.2 4.6 33 0.7 1.3 0.002* 
Affected MalesAffected MalesAffected MalesUnaffected SiblingsUnaffected SiblingsUnaffected Siblingst-test Difference vs References
DimensionnMeanSDnMeanSDP-Value
P<0.05)* Affected Males(age 23–76 years) Unaffected Siblings(age 20–81 years) 
SF-36 Scores        
General Health Scale 44 58.1 28.7 32 71.4 21.4 0.024* 
Role Emotional 44 89.2 19.9 33 98.0 5.5 0.007* 
Colorado PE-05 Musculoskeletal Scores        
Axial Deformity 47 0.9 1.4 33 0.2 0.8 0.008* 
Range of Motion 47 4.2 2.0 33 2.9 1.8 0.005* 
Gait 47 2.4 3.5 33 0.4 1.4 0.002* 
Left Ankle 47 3.3 5.0 33 1.0 2.9 0.015* 
Right Ankle 47 3.2 4.6 33 0.7 1.3 0.002* 

There was a positive association between the SF-36 General Health Scale scores and the following values of the Colorado PE-05 Scores. Gait (R -.45, p<.001), Range of Motion (R-.08, P=.508), Axial Deformity (R -.35, P<.001), Right Ankle (R -.42, p<.001), and Left Ankle (R-.49, p<.001). The association between the SF-36 Role Emotional Scales for affected males and the values of the Colorado PE-05 was also positive. Gait (R -.52, P<.001), Range of Motion (R - .30, P = .01), Axial Deformity (R -.54, P<.001), Right Ankle (R -.06, P<.001) and Left Ankle (R-.52, p<.001). No patients studied have acquired an inhibitor to Factor VIII. Obese males (BMI >30) had significantly greater impairment in their Range of Motion than non-obese males (4.59 vs (3.34), p<0.05) independent of whether or not they had hemophilia. These results are consistent with our clinical experience that mild Hemophilia A causes episodic bleeding, lack of recognition and delayed treatment leads to significant morbidity. The association with diabetes was unexpected. Future interventions will now focus on prevention and early treatment of ankle bleeds and will include strategies to reduce the risk of obesity.

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