Paradox pain sensitivity using cuff pressure or algometer testing in patients with hemophilia.

INTRODUCTION: Pain is a common comorbidity in patients with hemophilia (PwH) due to hemophilic arthropathy. This study aims to explore pain sensitivity in PwH methodologically investigating in cuff pressure testing compared to algometer testing. METHODS: 37 PwH and 35 healthy control subjects (Con) enrolled in this study. Joint health status was assessed. Subjective pain was evaluated using numeric rating scales. Pain sensitivity was measured with pressure algometry and cuff pressure algometry. Pressure pain thresholds of the algometer (PPTa) were measured at knee, ankle joints, and forehead. Subsequently, thresholds of cuff pressure were measured at the left and right lower legs (PPTcuff). In both, lower values represent higher pain sensitivity. RESULTS: PwH exerted a worse joint health status than Con. Pain sensitivity was higher in PwH compared to Con as PPTa of the knee and ankle joints were lower in PwH. No difference was observed in PPTa at the forehead. Contrastingly, lower pain sensitivity was detected in PwH by higher PPTcuff values compared to Con in both legs. CONCLUSION: While PPTa of the knee and ankle joints are lower in PwH, PPTcuff are higher in PwH compared to Con. This reveals a paradox situation, highlighting that PwH experience local, joint- and hemophilic arthropathy-related pain, whereas pain sensitivity of non-affected soft tissue structures is lower. The reasons explaining the PPTcuff results remain elusive but might be explained by coping strategies counteracting chronic joint pain, resulting in lower sensitivity at non-affected structures.

Physical activity and factor VIII levels in patients with haemophilia: A real-world prospective observational study.

INTRODUCTION: Regular physical activity (PA) is recommended for patients with haemophilia (PwH). For PwH it is crucial to ensure a sufficient factor level to prevent PA-induced bleedings. However, there is a gap in the literature dealing with specific factor levels, which are needed when performing specific types of PA. AIM: To provide data on factor VIII (FVIII) levels at the start of PA performed by PwH. METHODS: In this prospective 12-month real-world observational study, 23 PwH recorded every PA they performed and the FVIII levels at the start of the PA using a pharmacokinetic application. PA types were clustered according to the collision and injury risk into three categories (Cat I = low, Cat II = medium, Cat III = high risk). Haemophilia Joint Health Scores (HJHS) were performed at baseline, after 6 and 12 months. RESULTS: 795 PA sessions of Cat I, 193 of Cat II, and 23 of Cat III were documented. FVIII levels at the start of PA were different between categories (Cat I: 29.8 ± 32.1%, Cat II: 38.3 ± 33.4%, Cat III: 86.6 ± 29.2%). Out of all PA sessions, 145 (14%) were performed at a factor level of ≤3%. Three PA-induced bleeding occurred. Baseline HJHS was 14.5 ± 13.6 points and did not change throughout the study. CONCLUSION: This study provides real-life data on FVIII levels at the start of 1011 PA sessions. PwH are mainly active in low-risk sports with higher FVIII levels observed in Cat II and III, respectively. Only three PA-induced bleeding occurred, even though several PA were started with low FVIII levels.

Most subjectively affected joints in patients with haemophilia - what has changed after 20 years in Germany?

BACKGROUND: In patients with haemophilia (PwH), most frequently affected joints are the ankle, knee and elbow. Due to improved factor therapy in the last decades, these previous findings have to be verified in Germany. AIM: The aim of this study is to detect the most affected joint, evaluate the significance of the source of pain and determine the point prevalence of back pain in Germany today. PATIENTS AND METHODS: In a retrospective study, data of n = 300 patients with severe moderate and mild haemophilia were evaluated regarding the most affected joint, the most common source of pain, and the point prevalence of back pain. An anamnesis questionnaire and the German Pain Questionnaire were used for this assessment. RESULTS: The most affected joint in German PwH is still the ankle (41%), followed by the knee (27%) and the elbow (11%). The most common source of pain is also the ankle joint (32%). Back pain was also identified as one of the most common sources of pain, which is comparable to the elbow (elbow:15%; back:13%). The point prevalence in PwH for back pain was significantly higher compared to the general German population (P = .031). CONCLUSION: Our data showed that the ankle is still the most affected joint and the most common source of pain in Germany. These results also showed the relevance of back pain as a pain source. The evaluations also demonstrated the high point prevalence of back pain in PwH. Future therapies should also focus on the spine because joint changes affect posture.

Prevalence of pain in adult patients with moderate to severe haemophilia: a systematic review.

OBJECTIVES: Patients with haemophilia (PwH) often suffer from joint pain due to repetitive haemarthroses and resulting arthropathy. Literature focuses so far on pain causes, diagnosis or treatment. A summary of prevalence rates, providing facts on the absolute occurrence of pain, is not sufficiently described so far. This review aimed to explore and systematically review different pain conditions, focussing on prevalence rates of pain in adult PwH. METHODS: A review of English articles using PubMed and Web of Science was conducted in February 2020. The search strategy included patients with haemophilia A or B suffering from pain. The articles were selected based on defined PICOS-selection criteria. RESULTS: Out of 606 identified articles, 13 studies matched the given eligibility criteria and indicated pain prevalence rates. The weighted mean (WM) for the prevalence rate (varying timeframes) for chronic pain was 40% whereas for point prevalence the rate was WM=75%. Regarding pain intensity, findings of the EQ-5D-3L revealed moderate pain to be more present (61.0%) compared to extreme (11.6%). The main problem was the inconsistency of the definition of both acute and chronic pain as well as for prevalence types. CONCLUSIONS: Pain is a major problem in patients with haemophilia. Pain therapy should be carried out taking into account the difference between bleeding-related or arthropathy-related causes of pain. In addition, the intensity and duration of pain should be recorded consistently to better monitor therapy and allow comparison with existing data.

Aerobic exercise in patients with haemophilia: A systematic review on safety, feasibility and health effects.

BACKGROUND: Haemophilia is a congenital bleeding disorder going along with disease-specific joint complications and general health implications attributed to the lack of daily movement. Recent guidelines recommend physical activity for people with haemophilia (PwH). Yet, aerobic exercise in PwH is little studied and seldomly prescribed by clinicans. AIM: The aim of this systematic review is to investigate the safety, feasibility and health-related efficiency of AE in PwH. METHODS: A systematic literature search according to the PRISMA guidelines was conducted (PubMed, Web of Science). Inclusion criteria were defined using PICOS. Methodological quality was assessed via TESTEX. RESULTS: Out of 789 studies identified, seven studies (three randomized controlled, two controlled, two single-group prospective trails) were included. The TESTEX mean score was 8.1 (±3.8). AE was realized as aquatic exercise, nordic walking, treadmill running, bicycle riding and swimming. Neither bleeding rates nor the factor amount increased and AE led to diverse health-related improvements. CONCLUSIONS: Little research has been conducted evaluating AE in PwH. Yet, AE can be considered as safe and feasible when being supervised by experts. However, disease-specific recommendations for AE are difficult to provide. Therefore, experts can currently only back AE recommendations on experience and nonhaemophilia-specific general guidelines.

Sport and Venous Thromboembolism­Site, Accompanying Features, Symptoms, and Diagnosis.

BACKGROUND: The occurrence of venous thromboembolisms (VTE) in association with sporting activity has been described but not yet systematically explored. The aim of this study was to determine the sites at which VTE occur in athletes, the accompanying features, and the special features of the symptoms and diagnosis, so that physicians can take the findings into consideration. METHODS: A search of the literature in the databases PubMed, Web of Science, and Cochrane in accordance with the PRISMA criteria, together with a search of Google Scholar up to 29 February 2020. RESULTS: No observational studies were identified. A total of 154 case descriptions were evaluated: 89 on upper-extremity deep vein thrombosis (DVT), 53 on lower-extremity DVT, and 12 on pulmonary embolisms with no evidence of thrombosis. Ninety-five percent of the upper-extremity DVT involved the region of the subclavian/axillary vein. Thoracic outlet syndrome (38%), hereditary thrombophilia/a family history of VTE (16%), intensive training (12%), and the use of oral contraceptives (7%) were identified as accompanying features. The upper-extremity DVT occurred mainly in male strength athletes and ball sports players. The lower-extremity DVT were located in the lower leg/knee (30%), the thigh (19 %), or occurred in combination in the lower leg-to-pelvis region (30 %). The features accompanying lower-extremity DVT were hereditary thrombophilia/a family history of VTE (30%), trauma (25%), immobilization (21%), and the use of oral contraceptives (11%). The lower-extremity DVT were found in endurance sports and ball sports. The symptoms may be obscured by sport-specific symptoms/trauma, and diagnosis is often delayed. Early D-dimer determination is useful and is complemented by diagnostic imaging. CONCLUSION: VTE are found in association with sports. The background factors, the sites of VTE, the types of sports involved, and the accompanying features are all important to know. The symptoms may be obscured, and it may be difficult to reach the correct diagnosis. The possible presence of DVT must be borne in mind.