Joint bleeding, or haemarthrosis, is the most common type of bleeding episode experienced by individuals with haemophilia A and B. This leads to changes within the joints, including synovial ...proliferation, which results in further bleeding and chronic synovitis. Blood in the joint can also directly damage the cartilage, and with repeated bleeding, there is progressive destruction of both cartilage and bone. The end result is known as haemophilic arthropathy. The joints most commonly affected are the knees, elbows and ankles, although any synovial joint may be involved. In the ankle, both the tibiotalar and subtalar joints may be affected and joint bleeding and arthropathy can lead to a number of deformities. Haemophilic arthropathy can be prevented through regular factor replacement prophylaxis and implementing physiotherapy. However, when necessary, there are multiple surgical and non‐surgical options available. In early ankle arthropathy with absent or minimal joint changes, both radioisotopic and chemical synoviorthesis can be used to reduce the hypertrophied synovium. These procedures can decrease the frequency of bleeding episodes, minimizing the risk of articular cartilage damage. Achilles tendon lengthening can be performed, in isolation or in combination with other surgical measures, to correct Achilles tendon contractures. Both arthroscopic and open synovectomies are available as a means to remove the friable villous layer of the synovium and are often indicated when bleeding episodes cannot be properly controlled by factor replacement therapy or synoviorthesis. In the later stages of ankle arthropathy, other surgical options may be considered. Debridement may be indicated when there are loose pieces of cartilage or anterior osteophytes, and can help to improve the joint function, even in the presence of articular cartilage damage. Supramalleolar tibial osteotomy may be indicated in patients with a valgus deformity of the hindfoot without degenerative radiographic findings. Joint fusion, or arthrodesis, is the treatment of choice in the advanced stages of ankle arthropathy although total ankle replacement is currently available. Early ankle replacement components were associated with a poor outcome, but as implant designs have improved, there have been successful outcomes achieved. As the ankle is a commonly affected joint in many individuals with haemophilia, it is important to add to the knowledge base to validate indications and timing of surgical and non‐surgical interventions in ankle arthropathy.
Summary
Illness representations of chronic patients are important to explain adherence and preventive behaviours. However, it is unclear if the patient's objective health status may influence illness ...representations and perceived adherence. This study explored if health status and socio‐demographic characteristics influence illness representations and perceived adherence in haemophilic patients. Fifty patients (25 on‐demand and 25 on prophylaxis) ageing from 13–73, completed the Illness Perceptions Questionnaire‐Revised and the Morisky Medication Adherence Scale. Patients' cognitive illness representations were influenced by type of treatment, haemophilia severity, presence of inhibitor and co‐morbidity. Perceived chronicity was influenced by patient's age (P = 0.021). Perceived adherence was not influenced by the health status, but was affected by the relationship status (P = 0.048). Perceived adherence was predicted by perceived chronicity (β = 0.412; P = 0.003) and by emotions (β = −0.308; P = 0.023). Patient's health status seems to affect cognitive illness representations but not perceived adherence. Perceived chronicity and negative emotions, which affected perceived adherence, were not influenced by the health status. Physician–patient communication addressing perceived chronicity and emotions rather than patients' health status may influence patient's adherence. Psycho‐educational groups could be offered to promote patient's well‐being and adjustment to haemophilia, and improve adherence.
An open-label phase II, multicenter clinical trial was conducted at 11 Haemophilia Centres in Italy, Romania, and Turkey, to evaluate the pharmacokinetics (PK), efficacy, and safety of high purity, ...plasma-derived, double virus inactivated and double nano-filtered factor IX (pd-FIX) concentrate (Kedrion FIX), EudraCT Number: 2005–006186-14.
16 previously treated patients (PTPs) with severe or moderately severe haemophilia B were enrolled in the study. At enrolment, 14 underwent the first PK assessment (PK I), and the second PK (PK II) assessment was performed after six months of treatment (5 on-demand and nine prophylaxis) at the end of the study. PK parameters were evaluated by Non-Compartmental Analysis (NCA), One-Compartment model (OCM), and Two-Compartment Model (TCM). Efficacy of Kedrion FIX in all 16 patients was evaluated by the number of bleeding events, and clinical response following the infusions. Periodic FIX inhibitor assays and thrombogenicity tests were scheduled throughout the study to assess the safety of the drug.
As compared to the published data on PK of pdFIX, Kedrion FIX displayed a longer half-life (22.37–55.73 hrs), reduced clearance, and regular volume of distribution at PK I by both NCA and OCM. The comparison of outcomes of PK II with those of PK I by OCM, also showed significant changes, particularly in patients on prophylaxis, who showed some improved parameters of PK. Due to two outlier values at the end of the trial, the NCA parameters of PK I were not compared to those of PK II. Breakthrough bleeds were successfully treated with 1 or 2 infusions. No significant adverse events were observed during the study.
During the six-month clinical study period, the use of Kedrion FIX resulted in a safe and effective pd-FIX concentrate with excellent PK characteristics.
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Introduction
In haemophilia, recurrent joint bleeds are responsible for the development of chronic joint damage, because blood induces biochemical changes in joint structures. Joint degeneration is a ...long process, and structural damage is often preceded by joint dysfunction, which is represented by quantitative and qualitative changes in the contraction pattern of muscles around the joints. Muscle function in patients with haemophilia is still poorly investigated.
Aim
The aim of this 2‐year prospective study was to assess the changes in muscle function of lower limbs in a group of patients affected with haemophilia in San José, Costa Rica.
Methods
Muscle function of lower limbs was assessed by means of surface electromyography (sEMG) accomplished at study enrolment and after 2 years of follow‐up. Gluteus medius, vastus medialis, biceps femoris, gastrocnemius and tibialis anterior were examined. All patients underwent concurrent clinical examination using Haemophilia Joint Health Score (HJHS).
Results
Sixty patients aged 2‐43 years with severe haemophilia underwent clinical and sEMG evaluation. Thirty‐two patients (53%) had target joints. sEMG parameters were altered in all patients and were not correlated to the presence of target joints and/or an abnormal HJHS. Muscle function deterioration was observed after 2 years of follow‐up despite an unmodified HJHS.
Conclusions
Muscle function of lower limbs as detected by means of sEMG was impaired in patients with haemophilia irrespective of the presence of overt joint damage. sEMG is a simple and sensitive assessment tool able to detect muscle dysfunction and so favouring the implementation of early rehabilitation therapy.
Objective
Wan et al (Proc Natl Acad Sci USA, 105, 2008, 16432) demonstrated that RBCs rapidly and transiently release a spike of 300% more ATP shortly downstream from a short microfluidic ...constriction where the cells experience a sudden increase in shear stress. More recent work by Cinar et al (Proc Natl Acad Sci USA, 112, 2015, 11783), however, yielded no evidence for a similar spike in ATP release downstream of the constriction. Our aim was to determine whether a transient spike in mechanotransduction is the typical response of RBCs to the sudden onset of increased shear.
Methods
We investigate ATP release downstream of a microfluidic constriction for 15 participants using a luciferase‐based photoluminescent assay.
Results
While we observe mechanotransductive ATP release from blood drawn from all donors, we find evidence of a spike in ATP concentration after the microfluidic constriction for only 2 of 15 participants. No clear trends in ATP release are found with respect to the magnitude of the applied shear stress, or to the gender, age, or physical activity (Baecke) index of the donor.
Conclusions
In aggregate, all data acquired to date suggest that a spike in mechanotransductive ATP due to a suddenly applied increase in shear stress occurs in blood drawn from only 14% of the population.
Regular physical activity can increase joint stability and function, reduce the risk of injury, and improve quality of life of people with haemophilia (PwH). However, a recent review of the ...literature shows that appropriate physical activity and sport are not always promoted enough in the overall management of PwH. A group of Italian experts in haemophilia care undertook a consensus procedure to provide practical guidance on when and how to recommend physical exercise programmes to PwH in clinical practice. Three main topics were identified -haemophilia and its impact on movement, physical activity recommendations for PwH, and choice and management of sports activity in PwH- and ten statements were formulated. A modified Delphi approach was used to reach a consensus. The group also created practical tools proposing different physical activities and frequencies for different age groups, the Movement Pyramids, to be shared and discussed with patients and caregivers. In conclusion, in the opinion of the working group, physical activity can be considered as a low-price intervention that can prevent/reduce the occurrence of chronic diseases and should be further encouraged in PwH to obtain multiple physical and psychological benefits. Future research should include prospective studies focusing on participation in sports, specific risk exposure and clinical outcomes.
Although a number of studies have analysed so far the causes of death and the life expectancy in haemophilic populations, no investigations have been conducted among Italian haemophilia centres. ...Thus, the aim of this study was to investigate mortality, causes of deaths, life expectancy and co‐morbidities in Italian persons with haemophilia (PWH). Data pertaining to a total of 443 PWH who died between 1980 and 2007 were retrospectively collected in the 30 centres who are members of the Italian Association of Haemophilia Centres that chose to participate. The mortality rate ratio standardized to the male Italian population (SMR) was reduced during the periods 1990–1999 and 2000–2007 such that during the latter, death rate overlapped that of the general population (SMR 1990–1999: 1.98 95% CI 1.54–2.51; SMR 2000–2007: 1.08 95% CI 0.83–1.40). Similarly, life expectancy in the whole haemophilic population increased in the same period (71.2 years in 2000–2007 vs. 64.0 in 1990–1999), approaching that of the general male population. While human immunodeficiency virus infection was the main cause of death (45%), 13% of deaths were caused by hepatitis C‐associated complications. The results of this retrospective study show that in Italian PWH improvements in the quality of treatment and global medical care provided by specialized haemophilia centres resulted in a significantly increased life expectancy.
Summary
Total knee replacement (TKR) is a safe treatment for alleviating pain and restoring physical function in end‐stage arthropathy of the knee. First reports of TKR in haemophiliacs date back to ...the mid‐1970s, however detailed information on long‐term outcome is scarce. This study evaluated factors influencing the outcome of 116 primary TKRs performed consecutively over 14 years at a single institution. Haemostatic management is discussed in patients with and without inhibitors. Orthopaedic outcome was measured by using the Hospital for Special Surgery knee‐rating scale, knee flexion contracture and range of motion. At the end of follow‐up period (median duration: 5·1 years) 96 prostheses (83%) were still in place with a 7‐year removal‐free survival of 81%, similar between human immunodeficiency virus‐positive and ‐negative patients and lower in inhibitor than non‐inhibitor patients (44% vs. 87%; P < 0·05). Sixteen prostheses (14%) were removed for infection (nine) or aseptic loosening (seven) after a median of 4·5 years. Presence of inhibitors, continuous infusion, cementless prostheses and different primary surgeons were associated with an increased risk of infection; however, after adjustment, only primary surgeon was confirmed as an independent risk factor. These results show that TKR represents a safe and effective procedure in haemophiliacs if performed by a highly experienced surgeon.
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