RCT of a 6-month programmed sports therapy (PST) in patients with haemophilia - Improvement of physical fitness.

UNLABELLED: Physical fitness is of major importance for patients with haemophilia (PwH) but is highly influenced by bleeding episodes. Although some cohort studies describe an improvement of physical fitness after training intervention, randomized controlled studies (RCT) in PwH are still rare. AIM: The aim of this study was to prove the enhancement of physical work capacity in PwH by programmed sports therapy (PST). METHODS: This RCT includes a training period over six months. Sixty-four PwH with moderate (n = 5) to severe (n = 59) haemophilia A (n = 57) and B (n = 7) were randomized into two groups - training intervention group (IG) and control group (CG) by block randomization. Complex strength measurements, joint score, coordination check and a 12-min walking test were carried out before and after training intervention. RESULTS: Significant differences were tested in M. triceps brachii (Δ+0.62 N kg(-1) ), biceps brachii (Δ+1.25 N kg(-1) ), latissimus dorsi (Δ+0.59 N kg(-1) ), rectus abdominis (Δ+0.51 N kg(-1) ), biceps femoris (right: Δ+0.68 N kg(-1) ; left: Δ+0.59 N kg(-1) ) and the quadriceps femoris (right: Δ+0.71 N kg(-1) ; left: Δ+0.55 N kg(-1) ) after intervention between the two groups (all p ≤ 0.003). Furthermore, an increase in distance (Δ+171.5 m) covered in the 12-min walking test (P = 0.011) was observed. Regarding one-leg stand, a significant improvement (P = 0.037) in the IG (Δ+2.2 s right leg) after intervention could be determined. CONCLUSION: For the first time, a study with a corresponding number of adult PwH in a RCT-design showed that programmed sport therapy with specific instructions over 6 months has a positive effect on physical performance of PwH, independent of constitution and disease process.

Impact of joint status on contraction steadiness of m. quadriceps femoris in people with severe haemophilia.

Impaired contraction steadiness of lower limb muscles affects functional performance and may increase injury risk. We hypothesize that haemophilic arthropathy of the knee and the strength status of quadriceps are relevant factors which compromise a steady contraction. This study addresses the questions if impaired steadiness of the quadriceps is verifiable in people with haemophilia (PWH) and whether a connection between the status of the knee joint and quadriceps strength exists. A total of 157 PWH and 85 controls (C) performed a strength test with a knee extensor device to evaluate their bilateral and unilateral maximal quadriceps strength and steadiness. Isometric steadiness was measured by the coefficient of variation of maximum peak torque (CV-MVIC in %). For classification of the knee joint status the World Federation of Haemophilia (WFH) score was used. Lower steadiness (higher CV values) was found in PWH compared with C during bilateral [PWH vs. C; 0.63 (0.36/1.13) vs. 0.35 (0.15/0.72), median (Q25/Q75) P < 0.001] and unilateral trials [left leg: 0.70 (0.32/1.64) vs. 0.50 (0.23/1.04), P < 0.05; right leg: 0.68 (0.29/1.51) vs. 0.39 (0.18/0.68), P < 0.001]. PWH with a WFH score difference (≥1) between their extremities showed a less steady contraction in the more affected extremity (P < 0.05). More unsteady contractions have also been found in extremities with lower quadriceps strength compared with the contralateral stronger extremities (P < 0.001), whereby the weaker extremities were associated with a worse joint status (P < 0.001). The results of this study verify an impaired ability to realize a steady contraction of quadriceps in PWH and the influence of joint damage and strength on its manifestation.

Haemophilia & Exercise Project (HEP): the impact of 1-year sports therapy programme on physical performance in adult haemophilia patients.

Episodes of bleeding in people with haemophilia (PWH) are associated with reduced activity and limitations in physical performance. Within the scope of the 'Haemophilia & Exercise Project' (HEP) PWH were trained in a sports therapy programme. Aim of this study was to investigate subjective and objective physical performance in HEP-participants after 1 year training. Physical performance of 48 adult PWH was compared before and after sports therapy subjectively (HEP-Test-Q) and objectively regarding mobility (range of motion), strength and coordination (one-leg-stand) and endurance (12-min walk test). Sports therapy included an independent home training that had previously been trained in several collective sports camps. Forty-three controls without haemophilia and without training were compared to PWH. Of 48 PWH, 13 performed a regular training (active PWH); 12 HEP-participants were constantly passive (passive PWH). Twenty-three PWH and 24 controls dropped out because of incomplete data. The activity level increased by 100% in active PWH and remained constant in passive PWH, and in controls (P ≤ 0.05). Only mobility of the right knee was significantly improved in active PWH (+5.8 ± 5.3°) compared to passive PWH (-1.3 ± 8.6°). The 12-min walk test proved a longer walking distance for active PWH (+217 ± 199 m) compared to controls (-32 ± 217 m). Active PWH reported a better subjective physical performance in the HEP-Test-Q domains 'strength & coordination', 'endurance' and in the total score (+9.4 ± 13.8) compared to passive PWH (-5.3 ± 13.5) and controls (+3.7 ± 7.5). The 'mobility'-scale and one-leg-stand remained unchanged. Sports therapy increases the activity level and physical performance of PWH, whereby objective effects do not always correspond with subjective assessments.

Quadriceps strength, inter-extremity difference (IED) and joint status in adult persons with severe haemophilia in different age stages.

Quadriceps weakness seems to be a hallmark in adult persons with severe haemophilia (PWH). The purpose of this study was to compare PWH and non-haemophilic controls in different age stages with reference to joint status and quadriceps strength. Further aims were to examine the extent of strength-specific inter-extremity-difference (IED) and the prevalence of abnormal IED (AIED). A total of 106 adults with severe haemophilia (H) and 80 controls (C) had undergone an orthopaedic examination for classification of knee and ankle status using the WFH score. Quadriceps strength was evaluated unilaterally as well as bilaterally with a knee extensor device. Each group was divided into four age-related subgroups (HA/CA: 18-29, HB/CB: 30-39, HC/CC: 40-49, HD/CD: 50-70; in years). H presented a worse knee and ankle status than C indicated by higher WFH scores (P < 0.01). Regarding the age-matched subgroups only HB showed higher knee scores than CB (P < 0.05). The ankles were clinically more affected in HB-HD compared with those in age-matched controls (P < 0.05). H showed lower quadriceps strength than C (P < 0.05). In addition, all subgroups of H presented lower strength (HA: 10-17, HB: 19-23, HC: 35-36, HD: 53-61; in%, P < 0.05). IED was higher in H than in C [H: 12.0 (5.3/32.2) vs. C: 7.1 (2.9/10.9); Median (quartiles) in%, P < 0.001] and increased with age in H. We discovered an AIED in 35% of H. These findings highlight the importance for the early implementation of preventive and rehabilitative muscle training programmes in the comprehensive treatment of PWH.

Haemophilia & Exercise Project (HEP): subjective and objective physical performance in adult haemophilia patients--results of a cross-sectional study.

Recurrent musculoskeletal haemorrhages in people with haemophilia (PWH) lead to restrictions in the locomotor system and consequently in physical performance. Patients' perceptions of their health status have gained an important role in the last few years. The assessment of subjective physical performance in PWH is a new approach. This study aimed to compare the subjective physical performance of PWH with healthy controls and to correlate the results with objective data. Subjective physical performance was assessed via the new questionnaire HEP-Test-Q, which consists of 25 items pertaining to four subscales 'mobility', 'strength & coordination', 'endurance' and 'body perception'. HEP-Test-Q subscales were compared with objective data in terms of range of motion, one-leg-stand and 12-minute walk test. Forty-eight patients (44 ± 11 years) with haemophilia A (43 severe, three moderate) or B (two severe) and 43 controls without haemophilia (42 ± 11 years) were enrolled. PWH showed an impaired subjective physical performance in all HEP-Test-Q subscales and in the total score (52 ± 20) compared with controls (77 ± 10; P ≤ 0.001). Correlation analyses for the total score of the HEP-Test-Q and objective data revealed values ranging from r = 0.403 (one-leg-stand) to r = 0.757 (12-minute walk test) (P ≤ 0.001). PWH evaluated their physical performance poorer in comparison with healthy people. As self-assessment did not always correlate highly with objective data, objective examinations of physical performance in PWH should be complemented with subjective perceptions.

Ankle muscle activation in people with haemophilia.

Since normative surface EMG (SEMG) values for muscles acting at the knee joint are available for people with haemophilia, increasing interest is noticeable for other joints affected by haemophilic arthropathy. Adequate activity of shank muscles is an important key for appropriate postural control. The aim of this study was to determine differences in muscle activation patterns of lower leg muscles between people with and without haemophilia during upright standing. SEMG of tibialis anterior (TA), fibularis longus (FL), lateral (LG) and medial (MG) heads of gastrocnemius, and soleus (SO) muscles of both sides were recorded in 25 haemophilic patients (H) and 25 non-haemophilic control subjects (C) while standing on even ground. The Gilbert-Score was used to assign sides to major (H-MA) and minor (H-MI) affected ankle joints in H. To normalize the SEMG amplitudes, amplitude ratios (percentage of cumulated activity) were calculated. Compared to controls, TA ratios showed higher and MG reduced levels in both H groups (P < 0.01). In the H-MA subgroup of H, FL also joined the TA behaviour whereas SO had similar activation direction as MG. Although possible descending influences from the knee joints cannot be excluded, this can be interpreted as a compensational mechanism due to the severity of the orthopaedic status of the ankle, which with increasing heaviness is accompanied by reduced plantar flexion capability. However, ankle joint integrity appears to be reduced in H, with TA and MG seeming to play key roles for neuromuscular control of upright posture.

SEMG activation patterns of thigh muscles during upright standing in haemophilic patients.

Although electromyography (EMG) is a common method to evaluate muscle activity, studies utilizing EMG in haemophilic patients are rare. The haemophilic arthropathy, resulting in altered afferent information is expected to cause disturbed activation and inter-muscular coordination patterns in haemophilic subjects. The aim of this study was to determine differences of selected knee muscles between haemophilic patients and non-haemophilic subjects during upright standing. Surface EMG (SEMG) amplitudes of rectus femoris, vastus medialis (VM), vastus lateralis (VL) and biceps femoris (BF) muscles of both sides were measured in 27 haemophilic patients (H) and 26 control subjects (C) while standing on an even surface. Data from both sides were pooled in C, but data of H were subdivided further according to major (H-MA) and minor (H-MI) affected joints. To normalize the data, amplitude ratios (percentage of cumulated activity) were calculated as well. Regardless of whether H-MA or H-MI was compared with C, amplitudes of all extensor muscles reached significantly higher levels in H (P < 0.05). SEMG amplitude ratios also differed between H and C. Independent of subgroup, BF showed significantly reduced activation ratios (P < 0.01). Only the ratios of VM and VL of H-MA could replicate the observed amplitude differences to C (P < 0.05). These findings show that while standing, haemophiliacs maintain the necessary stability demands through increased extensor activities and modulated coordination patterns. Although all thigh muscles of haemophiliacs are characterized by distinct atrophy, increased amplitude levels could be proved for the knee extensor muscles only. Therefore, general atrophy-related effects cannot explain these results.

Development and validation of a new questionnaire for the assessment of subjective physical performance in adult patients with haemophilia--the HEP-Test-Q.

Specific research studies for the investigation of physical performance in haemophilic patients are rare. However, these instruments become increasingly more important to evaluate therapeutic treatments. Within the frame of the Haemophilia & Exercise Project (HEP), a new questionnaire, namely HEP-Test-Q, has been developed for the assessment of subjective physical performance in haemophilic adults. In this article, the development and validation of the HEP-Test-Q is described. The development consisted of different phases including item collection, pilot testing and field testing. The preliminary version was pilot-tested in 24 German HEP-participants. Following evaluation and preliminary psychometric analysis, the HEP-Test-Q was revised. The final version consists of 25 items pertaining to the domains 'mobility', 'strength & coordination', 'endurance' and 'body perception', which was administered to 43 German haemophilic patients (43.8 +/- 11.2 years). Psychometric analysis included reliability and validity testing. Convergent validity was tested correlating the HEP-Test-Q with SF-36, Haem-A-QoL, HAL and the Orthopaedic Joint Score. Discriminant validity tested different clinical subgroups. Patients accepted the questionnaire and found it easy to fill in. Psychometric testing revealed good values for reliability in terms of internal consistency (Cronbach's alpha = 0.96) and test-retest reliability (r = 0.90) as well as for convergent validity correlating highly with Haem-A-QoL, HAL and SF-36. Discriminant validity testing showed significant differences for age, hepatitis A and hepatitis B and the number of target joints. HEP-Test-Q is a short and well-accepted questionnaire, assessing subjective physical performance of haemophiliacs, which might be combined with objective assessments to reveal aspects, which cannot be measured objectively, such as body perception.

[Maximal isometric strength measures of the quadriceps muscles. Feasibility and reliability in patients with haemophilia]. / Isometrische Maximalkraftmessungen der Quadrizepsmuskulatur. Durchführbarkeit und Reliabilität bei Patienten mit Hämophilie.

UNLABELLED: The quadriceps femoris muscle (QF) plays an important role in locomotion. However, assessing the total number of attempts to evaluate the maximal isometric strength (Fmaxiso) regarding reliability and feasibility remain less characterised. PATIENTS, METHODS: 28 patients with haemophilia (H) (26 severe, 2 moderate) and 27 healthy controls (C) matched for age (H: 44 ± 11, C: 42 ± 12) and anthropometric data were measured separately for the left and right leg for Fmaxiso of QF using m3 diagnos (SCHNELL®). We repeated the Fmaxiso measures after 48 h in 14 H and 13 C. RESULTS: The system m3 diagnos showed strong reliability (ICC = 1.0; SEM = 0.0; CA = 1.0). H and C demonstrated significant differences in Fmaxiso (H r = 153 Nm, l = 164 Nm; K r= 289 Nm, l = 280 Nm; p ≤ 0.001). Additionally, H and C revealed significant differences between the 1st and 3rd to 6th attempts. No differences were observed between the 3rd, 4th, 5th and 6th attempts. CONCLUSION: Both groups showed high test-retest-reliability of Fmaxiso (ICC/SEM: H l = 0.98/7.1 r = 0.99/4.9; K l = 0.69/11.3 r = 0.95/5.8). Starting from the 3rd attempt, reliable measurements of the Fmaxiso in patients suffering from severe haemophilia are feasible.

Cross sectional study to investigate the influence of treatment regimes on the development of haemophilic arthropathy.

Haemophilic arthropathy is often present in patients with severe haemophilia. New studies demonstrate that only a small amount and a short exposure of blood in vitro are able to induce an impairment of the joint cartilage. Free blood in the joint leads to different mechanisms and includes cartilage and bone damage induced by a release of macrophages and monocytes followed by activated cytokines and inflammatory processes. Another mechanism is mediated by free iron resulting in synovitis and synovial hyperplasia and a neoangiogenesis on the base of VEGF release is common. At worst, these processes result in a complete picture of haemophilic arthropathy reducing quality of life. Few studies are available about the influence of factor treatment regime, e. g. prophylaxis or on-demand therapy, on the development of haemophilic arthropathy. However these studies investigated in most cases children. Therefore, it is still impossible to give recommendations for the right treatment in adult haemophilic patients because data are still lacking. For that reason, we attempt to initiate the HemArthro-Project to investigate the influence of treatment therapy on the development of arthropathy in adult haemophilic patients. This study includes the investigation of functional musculoskeletal parameters for the description of joint function in maximal 500 severe haemophilic patients parted into two groups of treatment regime (prophylaxis vs. on-demand). The investigators are seeking further assistance from the haemophilic treatment centers for the support of this study.

Climbing therapy under PK-tailored prophylaxis.

UNLABELLED: Climbing has a low risk of injury and strengthens the entire musculature. Due to its benefits in physical and mental health as well as its high fun factor climbing is an established way of therapy. So far, the usefulness of climbing therapy has not been shown for people with haemophilia (PWH). A crucial requirement for physical activity in PWH is regular prophylaxis. As the patient's individual pharmacokinetic (PK) response varies significantly, PK-tailored prophylaxis may decrease bleeding frequency. CASE REPORT: We describe a man (age 25 years) with severe haemophilia A who took part in an 8.5-month weekly climbing program under PK-tailored prophylaxis. Bleeding frequency, factor consumption, joint health (Haemophilia Joint Health Score, HJHS), quality of life (Haemo-QoL-A) and climbing performance (UIAA scale) were assessed before and after the training. Prior to the study, the patient was on demand treatment. The patient was started on standard prophylaxis for a 2 months period and then observed for 6.5 months under PK-tailored prophylaxis. PK-tailored prophylaxis was targeted to a trough level of 1-3%. For high-impact activities a factor activity >15%, for low-impact activities a factor activity >5% was suggested. RESULTS: Climbing therapy was safe. The bleeding rate decreased from 14 (2012) to 1 (during the study period of 8.5 months). The one bleeding event was due to a missed infusion and was not triggered by physical activity. The elimination half-life using Bayesian statistics was determined to be 16h. Using this half-life for PK-tailored prophylaxis reduced the factor VIII consumption in comparison to standard prophylaxis. Joint health was particularly improved in the categories range of motion and swelling. Quality of life scores stayed at a high level. Climbing performance improved by 1 grade. CONCLUSION: The combination of PK-tailored prophylaxis with therapeutic climbing improved clinical outcome in this young adult with severe haemophilia. The tailored concept for high- and low-impact activities appeared to be safe.

[Food consumption and dietary behaviour in haemophilia patients before and after a nutrition consultation]. / Lebensmittelkonsum und Ernährungsverhalten bei Patienten mit Hämophilie vor und nach Ernährungsberatung.

UNLABELLED: In over two-thirds of deaths, nutrition is a determining factor. Nutritional condition and dietary recommandations are unspecified in the haemophilia treatment. Aim of this study was to examine the food consumption and dietary behaviour in affected patients before and after a nutrition consultation. PATIENTS, METHODS: Data were assessed via questionnaires and compared between 38 patients with haemophilia (PwH) and 20 controls without haemophilia. Furthermore, in a randomised controlled trial 11 patients with haemophilia (PwH-I) took part in an adapted nutrition consultation and were supervised over six months as opposed to 12 patients with haemophilia (PwH-O) without intervention. PwH were compared to controls more pleased with their weight (53 vs. 40%), used more nutrition consultations in the past (53 vs. 15%) and consumed more dairy products (40 vs. 15%) and fruits (45 vs. 30%). RESULTS: After nutrition consultation PwH-I were better informed about their own blood values than PwH-O. The nutrition rated high in both groups, but PwH-I were more mindful of the feeling of satiety (9 vs. 36%) compared to PwH-O (33 vs. 17%). Moreover, PwH-I ate less under stress and/or out of boredom, showed a higher satisfaction regarding their weight and increased the liquid intake (55 vs. 73%), which remained unchanged in PwH-O with 42%. Compared to PwH-O, PwH-I ate more roughage, low-fat food, fish and fruits, therefore consuming less coffee/tea. CONCLUSION: Food consumption and dietary behaviour are similar between patients with haemophilia and controls without haemophilia. A nutrition consultation affected the food consumption and dietary behaviour in patients with haemophilia positively and can consequently contribute to preservation of health and prevention of nutritional diseases.

[Age-related activation of the muscles during upright standing in patients with haemophilia]. / Altersabhängige Ansteuerung der Muskulatur im Stand bei Patienten mit Hämophilie.

Thehaemophilicarthropathyaffects thefunction of theknee joint muscles. The aim of thisstudywas to investigatethe myoelectrical signal ofknee jointmusclesin different agestages during upright standing. Surface EMG (SEMG) amplitudes of quadriceps, hamstrings and gastrocnemii were measured in 191 patients with severe haemophilia A (n=164) and B (n=27) while standing on an even surface. After an age-based classification of patients into the subgroups H(A): 17-29 (n = 37), H(B): 30-39 (n = 50), HC: 40-49 (n = 61), H(D): 50-70 in years (n = 43) the clinical WFH score for the ankle and knee joint was determined. To normalize the SEMG values amplitude ratios (percentage of cumulated activity) were calculated with respect to the specific limb. With increasing age, the patient showed descriptively a deterioration of the joint situation. The extensors of the knee joint reached significantly higher absolute and percentage levels in the muscle activity with increasing age (p < 0.05). The absolute amplitude values of the Mm. gastrocnemii showed no differences in the age groups while the relative levels were decreased. The present study shows that patients with increasing age and degree of haemophilic arthropathy develop a modified control strategy during upright standing, in the form of a shift from the plantar flexors to the extensors of the knee joint.

[Development and evaluation of a dance-based exercise therapy for patients with haemophilia]. / Entwicklung und Evaluierung einer tanzbasierten Bewegungstherapie für Patienten mit Hämophilie.

UNLABELLED: So far, the use of methods derived from creative arts has not been considered in the haemophilia treatment. The AIM was to investigate the expectations for a dance-based exercise therapy for patients with haemophilia and the extent of its acceptance. PATIENTS, METHOD: The one-hour dance-based exercise therapy was offered to 30 haemophilia patients (HI30) (49 ± 11, 30-67 years). For the evaluation of expectations, questionnaires were created and filled out by participants before and after the intervention. Additionally, 19 haemophilia patients (HF) and 20 controls without haemophilia (KF) who did not participate in the intervention were also questioned. The RESULTS show that haemophilia patients have more experience in dance than controls (HI30:62%, HF:74%, KF:45%). In contrast, the proportion of those who are currently dancing is higher in controls without haemophilia (HI30: 17%, HF: 10%, KF:26%). The termination of dance activity in patients with haemophilia who were part of the intervention was mainly due to pain (HI30: 40%, HF: 29%, KF: 0%), whereby controls without intervention terminated the dance activity mainly due to lack of time (HI30: 30%, HF: 57%, KF: 56%). Ultimately, 24 out of 30 patients with haemophilia (HI24) completed the intervention. All HI24 met their expectations. 38% felt limited by haemophilia while carrying out the exercises. The majority of the participants were able to follow the exercises well (96%) and were did not overstrain physically (92%) nor mentally (87%), also 79% did not have pain. 23 of HI24 (96%) can envision a continuation of the dance-based exercise therapy. CONCLUSION: The experience with the dance-based exercise therapy was predominantly positive. It represents an alternative sports therapy programme for patients with haemophilia. Further studies are needed in order to make statements concerning the long-term use of such training.