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
| Characteristic . | Affected Males . | Control Males . | P-Values (Affected vs Control) . | Carrier Females . | Control Females . | P-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 |
| Characteristic . | Affected Males . | Control Males . | P-Values (Affected vs Control) . | Carrier Females . | Control Females . | P-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 Males . | Affected Males . | Affected Males . | Unaffected Siblings . | Unaffected Siblings . | Unaffected Siblings . | t-test Difference vs References . |
|---|---|---|---|---|---|---|---|
| Dimension . | n . | Mean . | SD . | n . | Mean . | SD . | P-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 Males . | Affected Males . | Affected Males . | Unaffected Siblings . | Unaffected Siblings . | Unaffected Siblings . | t-test Difference vs References . |
|---|---|---|---|---|---|---|---|
| Dimension . | n . | Mean . | SD . | n . | Mean . | SD . | P-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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