Study Shows Pain and Mobility Issues Common with Moderate Hemophilia

Patients ages 15 and older report problems more typical of severe disease

by Patricia Inácio, PhD

Progressive joint disease caused by repeat bleeds, a condition known as hemophilic arthropathy, affects people with moderate hemophilia in Nordic countries regardless of age, commonly causing them pain and restricting their mobility, a study found.

Middle-age patients, those 41 to 50 years old, felt their overall quality of life poorer than that of general public in Norway, with a similar trend seen in those ages 61 to 70, possibly reflecting more severe arthropathy with age.

“But otherwise, [health-related quality of life] of patients with moderate haemophilia aligned with the general population,” the researchers wrote.

Regular use of preventive treatment, or prophylaxis, and efforts to promote joint health may improve life quality and physical activity levels in this patient group, they noted.

The study, “Health-related quality of life and physical activity in Nordic patients with moderate haemophilia A and B (the MoHem study),” was published in the journal Haemophilia.

43% of patients reported pain or discomfort, and 30% had mobility issues

Hemophilia is caused by deficiencies in, or a lack of, crucial blood clotting factors, leading to an impaired ability to control excessive bleeding. In hemophilia A, individuals lack or have a faulty factor VIII (FVIII), while in hemophilia B, the deficiency lies in factor IX (FIX).

The current standard of care for hemophilia consists in administering a working version of the missing clotting factor protein to prevent spontaneous bleeds and other complications, including chronic arthropathy (joint disease) and disability.

On-demand treatment is often the choice for people with moderate hemophilia, while those with severe disease often use prophylaxis.

Studies, however, have found hemophilic arthropathy and “a severe bleeding phenotype” in some with moderate disease. Poorer health-related quality of life (HRQoL) and limited physical activity also have been reported in these patients.

To assess HRQoL and physical activity with moderate hemophilia, and relate them to patients’ preferred treatment modality, coagulation factor levels, and the presence of hemophilic arthropathy, a team led by researchers at Oslo University Hospital in Norway analyzed data from the MoHem study in joint health and hemophilia treatment.

Data collected covered 104 patients (61 with hemophilia A and 43 with hemophilia B), ages 15–84 (median age, 41), attending any of five comprehensive care centers in Norway, Sweden, and Finland taking part in the MoHem study between January 2017 and October 2019.

Of them, 36 patients were on prophylaxis and 68 were using on-demand treatment.

HRQoL was assessed by the EQ-5D questionnaire, which uses a descriptive system to evaluate five aspects of life: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Scores for each dimension — rated as levels, with no problems as level 1, some problems as level 2, and extreme problems as level 3 — then were combined into an index value ranging from less than zero to one, with higher scores indicating better health.

The questionnaire also included the visual analogue scale for patients’ views of their overall health, with scores ranging from zero (worst imaginable health) to 100 (best imaginable health). Patient-reported HRQoL were compared to age-matched data from the general population EQ-5D index for Norway.

Patients’ overall EQ-5D index was a median of 0.85, with a corresponding VAS score of 80. No significant differences in the index score or VAS were seen regarding the type of treatment, prophylaxis (EQ-5D index 0.80, VAS 80) vs. on-demand (EQ-5D index 0.85, VAS 80), or regarding clotting factor levels or type of hemophilia.

However, a trend was observed for better VAS scores (median of 88) among patients with a ratio of FVIII/FIX greater than 3 international unites per deciliter (IU/dL) compared to those with a 3 or lower IU/dL (median VAS of 80). Of note, this ratio is used to assess the functioning of clotting factors in the blood, and a value greater than 3 IU/dL suggests that an adequate amount of these clotting factors for normal blood clotting.

Pain and problems with mobility were the most commonly reported issues on the EQ-5D questionnaire: 43% of patients experienced moderate pain or discomfort, and 30% had mobility problems. Anxiety and depression were reported by 23% of patients.

“Pain and mobility were the most commonly affected dimensions at EQ-5D, which have also been observed in severe haemophilia,” the researchers wrote.

The EQ-5D index showed a significant negative correlation — indicating that as one increases, the other decreases — with the Hemophilia Joint Health Score (HJHS) and the Hemophilia Early Arthropathy Detection with Ultrasound (HEAD-US). The same was seen for age and the annual number of joint bleeds.

HJHS evaluates joint health, and the HEAD-US is used to assess structural joint damage. A higher score on either scale reflects poorer joint health.

A moderately negative correlation also was seen between VAS, or patient views of overall health status, and HJHS scores.

Higher activity levels seen in adult group on regular preventive treatment

Patients then were grouped by age: 15-34 (46 people), 35-54 (26 people) and 55 years and older (32 people). Patients older than 35 had significantly lower EQ-5D index and VAS scores than those in the 15-34 age group.

When compared to the general population, patients ages 41-50 had significantly lower EQ-5D index and VAS scores, with a similar trend on the EQ-5D index seen in patients ages 61-70.

Physical activity was assessed using the International Physical Activity Questionnaire Short Form and expressed as a metabolic equivalent of task (a MET unit). MET estimates the amount of oxygen and calories used by the body during physical exercise.

Only patients on prophylaxis in the 35-54 age group reported significantly higher physical activity levels when compared with those using on-demand treatment, as evidenced by higher METs. Those on prophylaxis had a median of 3,884 MET-minutes each week, while on-demand patients had a median of 2,346 weekly MET-minutes. Otherwise, physical activity showed no association with treatment choice, FVIII/FIX levels, or hemophilia type.

No significant differences were seen in annual hospitalization rates or absences from school or work between those on preventive or on-demand treatment. A trend toward more days in the hospital, however, was seen for on-demand treatment patients compared with those on prophylaxis (16 days vs. two days).

“A more widespread use of early prophylaxis in moderate haemophilia may improve joint health and influence positively on their HRQoL and [physical activity],” the researchers concluded.

Hemophilia News Today, January 2024

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