Gaining Insight Into the Complexity of Pain in Patients With Haemophilia

Pain interference

时间窗: At one year follow-up (T2)

The BPI was used to evaluate how much pain interferes with patient's daily activities. This was assessed by seven items, resulting in a total pain interference score. Minimum score 0, maximum score 10. The higher the score, the more pain interference.

Signs of neuropathic pain

时间窗: At baseline (T0)

The Douleur Neuropathique en 4 questions (DN4) was applied as a screening tool for the presence of a neuropathic pain component. Minimum score 0, maximum score 10, a score of ≥4/10 was used as a cut-off.

Pain severity

时间窗: At one year follow-up (T2)

The BPI was used to evaluate the individual's pain experience within the last 24 hours by four items, resulting in a total pain severity score. Minimum score 0, maximum score 10. The higher te score, the higher the pain severity.

Signs of central sensitization

时间窗: At baseline (T0)

The Central Sensitisation Inventory (CSI) part A was used to identify signs of central sensitization (CS) i.e. increased sensitivity of nociceptive neurons in the central nervous system.The presence of 25 pain-related psychological, cognitive and functional signs are scored from 0 (never) to 4 (always). A total score exceeding ≥40/100 indicated central sensitization.

Joint structure US

时间窗: At baseline (T0)

Ultrasound (US) examinations will be performed with a linear probe (3-13 MHz) Esaote, type MyLab Gamma, Genova, Italy).The Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) scanning procedure and scoring method will be performed by one of our investigators. A score of 0/8 (normal bone 0/2, normal cartilage 0/4, absent hypertrophic synovium 0/2) is considered normal. A score above 1/8 is considered as abnormal.

Pain Catastrophizing

时间窗: At baseline (T0)

The Pain Catastrophizing Scale (PCS) asked participants to reflect on previous painful experiences and to rate their degree of catastrophic thinking in the content domains of rumination, magnification and helplessness. A score of 0 (not at all) to 4 (all the time) was indicated for each of the 13 items, resulting in a total score range of 0-52. Higher scores were associated with higher levels of pain catastrophizing.

Fear Avoidance and Beliefs

时间窗: At baseline (T0)

The fear avoidance and beliefs questionnaire (FABQ) will be used to assess fear avoidance behaviors. The first five items question physical activity, the other 11 activities work. A minimum score is 0, maximum 24. Higher scores indicate fear avoidance behaviors.

Haemophilia Activity Limitations

时间窗: At baseline (T0)

The Haemophilia Activity List (HAL) was used to assess activity limitations and participation restrictions people with haemophilia suffer with. A sum score and component scores can be calculated, resulting in scores ranging from 0-100. Lower scores represent higher levels of participation restrictions.

Illness perceptions

时间窗: At one year follow-up (T2)

The illness perceptions questionnaire (B-IPQ) includes nine items ranging from 0 (minimum) to 10 (maximum) and questions the perceptions related to the patients disease. No total score exists, as each item is scored individually. Higher scores indicate more negative or unhelpful illness perceptions. A change score between baseline (T0) and one year follow-up (T2) will be calculated.

Physical activity

时间窗: At one month follow-up (T1)

The International Physical Activity Scale (IPAQ) questions the hours of physical activity over the last week. Based on the patient's answers a MET-minute score is calculated (MET-minutes x weight in kilograms/60kilograms)

Life quality

时间窗: At one year follow-up (T2)

The EQ-5D-5L was used to assess quality of life. From five items investigating the impact of their disease, a health utility score was calculated. Additionally, the questionnaire consists of a visual analogue scale (VAS) labelled from 0: "worst imaginable health state," to 100 "best imaginable health state" providing the EQ-VAS.

Pain localisation

时间窗: At one year follow-up (T2)

The body chart of the Brief Pain Inventory (BPI) was used to investigate painful body sites.

Warm and cold detection threshold

时间窗: At baseline (T0)

Thermal hyper or hypo esthesia were assessed with a thermode attached at the dominant wrist by use of a validated Quantitative Sensory testing protocol with the Medoc TSA-2 device.

Joint structure MRI

时间窗: At baseline (T0)

Magnetic Reasoning Imaging (MRI) of the ankles will be performed with a 3T-magnet (GE Signa Premier, GE Healthcare, Milwaukee, USA).Joint images will be classified with the international Prophylaxis Study Group (IPSG) scale. Joints will be classified as abnormal if talocrural joints or subtalar joints were positive at IPSG-score. Joints will be considered healthy if the total score was of 1/17.

Anxiety and Depression

时间窗: At baseline (T0)

The Hospital Anxiety and Depression Scale (HADS) was used to establish symptoms of anxiety and depression. This 14-item questionnaire consists of two subscales each including 7 items, the first to identify anxiety and the second depression. Individual items were scored from 0 to 3, resulting in a total range score of 0-21 for each subscale. A score of ≥8/21 was determined as a cut-off, indicating anxiety and depression.

Physical endurance ability

时间窗: At baseline (T0)

The 2 minutes walking test (2MWT) was used as a performance-based test to assess their functional activity. Subjects were asked to walk as far as possible for two minutes in a 30 meters flat corridor, resulting in the walking distance in meters.

Physical functioning

时间窗: At baseline (T0)

The Timed Up \& Go (TUG) consists of asking the patient to sit on a standard armchair; stand up and walk 3 meters; turn around at the line and walk back to the chair and sit down at a normal pace.

Joint function

时间窗: At baseline (T0)

Joint function of the ankles, knees and ankles was assessed with the HJHS 2.1. Minimum score is 0, maximum, 20. The higher the score the more functional limitations. HJHS scores are considered positive when scores reach 1/20.

Warm and cold pain thresholds

时间窗: At baseline (T0)

Thermal hyper or hypo algesia were assessed with a thermode attached at the dominant wrist by use of a validated Quantitative Sensory testing protocol with the Medoc TSA-2 device.

Mechanical pain thresholds

时间窗: At baseline (T0)

Mechanical local and widespread hyperalgesia indicated by lower pressure pain thresholds were assessed with a digital algometer at the knee joints, ankle joints and forehead. This by use of a validated quantitative sensory testing protocol.

Temporal summation of pain

时间窗: At baseline (T0)

Temporal summation (or bottom-up sensitization) of pain was assessed by use of a 60g Von Frey monofilament at the medial knee and dorsal side of the wrist of the dominant side.

Conditioned Pain Modulation

时间窗: At baseline (T0)

Dysfunctional endogenous pain inhibition (as form of central pain processing) was assessed by a validated protocol applying the Medoc TSA-2 device with thermodes attached at both wrists.