How mild is mild haemophilia?

INTRODUCTION: People with mild haemophilia (PWMH) experience sporadic bleeds and are less likely to receive an early diagnosis, appropriate treatment and medical care. Arthropathy is a key determinant of health-related quality of life (QoL), producing pain, limitations in mobility and daily activities. The aim of this study is to evaluate the incidence, risk factors and QoL associated with arthropathy in PWMH. MATERIALS AND METHODS: Observational, cross-sectional cohort study. Data were collected in a single interview and evaluated by a physiotherapist and an orthopaedist and analysed on demographics; baseline factor levels; as well as clinical (Haemophilia Joint Health Score [HJHS]), ultrasound (Haemophilia Early Arthropathy Detection with Ultrasound [HEAD-US]), radiological (Pettersson score [PS]), pain (visual analogue scale [VAS]) and QoL evaluations. We defined arthropathy when at least one of the joints shown with a HEAD-US score ≥ 1. RESULTS: Eighty-five patients and 510 joints were included. Patients' mean age was 35.9 years-old. Median age was 44.2 in patients with arthropathy versus 14.9 in patients without; the difference was statistically significant (p < .001). In patients over 20 years old, 90.5% shown arthropathy. Only 24 (28%) patients had no joint damage (HEAD-US = 0), and 61 (72%) had at least one joint with a HEAD-US ≥ 1. The ankle was the most affected joint. Patient age was found to be the most important risk factor associated with the development of arthropathy. CONCLUSIONS: Joint damage as a result of prior hemarthrosis was the most relevant factor associated with lower QoL, and emphasised the importance of early diagnosis and appropriate management in this particular population.

Tratamiento por vía artroscópica de pacientes con el diagnóstico de plica sinovial de rodilla / Arthroscopic treatment of patients diagnosed with synovial knee plica

Introducción: la PS se puede presentar de forma aislada o asociada a otras enfermedades, pero su responsabilidad como causa de dolor de la articulación se justifica cuando no se detectan otras alteraciones intraarticulares que expliquen los síntomas o cuando se asocia a otras enfermedades y se observa la PS vascularizada e irritada. El diagnóstico positivo es difícil tanto desde el punto de vista clínico como imagenológico, de allí que la artroscopia constituye el estándar de oro, para confirmar su presencia y realizar el tratamiento. Objetivo: evaluar la efectividad del tratamiento artroscópico en la percepción de la calidad de vida relacionada con la salud en 72 pacientes con plica sinovial. Método: se realizó un estudio de intervención terapéutica del tipo antes-después, prospectivo, longitudinal, cuasi–experimental, en el servicio de Ortopedia y Traumatología del Hospital Carlos Manuel de Céspedes de Bayamo, en el periodo comprendido de enero 2017 a diciembre 2018, al tratarse de un estudio cuasi-experimental, se llevó a cabo un análisis intragrupo, comparando los datos pre y postratamiento. Resultados: prevaleció el sexo femenino, en las edades comprendidas entre los 30 a 44 años, las plicas suprapatelares fueron frecuentes. La manifestación clínica más frecuente fue el dolor, seguido de la crepitación. La escala analógica visual mostró mejoría con disminución estadísticamente significativa. Conclusiones: se demostró la efectividad de la artroscopia. La complicación más frecuente fue la hemartrosis posquirúrgica(AU)

Introduction: PS can occur in isolation or associated with other diseases, but its responsibility as a cause of joint pain is justified when other intra-articular alterations that explain the symptoms are not detected or when it is associated with other diseases and the PS vascularized and irritated. Positive diagnosis is difficult both from a clinical and imaging point of view, hence arthroscopy is the gold standard, to confirm its presence and carry out treatment. Objective: to evaluate the effectiveness of arthroscopic treatment in the perception of health-related quality of life in 72 patients with synovial plica. Method: a prospective, longitudinal, quasi-experimental, before-after, therapeutic intervention study was carried out in the Orthopedics and Traumatology department of the Carlos Manuel de Céspedes Hospital in Bayamo, in the period from January 2017 to December 2018, As it was a quasi-experimental study, an intragroup analysis was carried out, comparing the pre and post-treatment data.Results: the female sex prevailed, in the ages between 30 to 44 years, suprapatellar plicae were frequent. The most frequent clinical manifestation was pain, followed by crepitus. The visual analog scale showed improvement with a statistically significant decrease. Conclusions: the effectiveness of arthroscopy was demonstrated. The most frequent complication was postoperative hemarthrosis(EU)

Inhibition of Fenton reaction is a novel mechanism to explain the therapeutic effect of intra-articular injection of PRP in patients with chronic haemophilic synovitis.

INTRODUCTION AND AIM: Haemarthroses cause major morbidity in haemophilia resulting in chronic haemophilic synovitis (CHS) and arthropathy. Oxidation of haemoglobin-coupled iron released in synovium after haemolysis induces chondrocytes death and cartilage damage, allowing postulate using iron-chelating drugs as potential therapeutic tool for haemophilic joint damage. Considering that albumin, the most abundant plasma protein, is a physiologic iron chelator, we aim to demonstrate that impediment of haemoglobin oxidation is exerted by plasma as a mechanism involved in the therapeutic effect of intra-articular injection of platelet-rich plasma in CHS. METHODS: Oxidation of haemoglobin (Hb) to methaemoglobin (MeHb) through Fenton reaction was induced in vitro by addition of potassium ferricyanide in the presence or absence of peripheral blood-derived platelets-rich or platelets-poor plasma (PRP/PPP) or albumin. The relevance of in vitro findings was analysed in synovial fluid (SF) samples from one patient with CHS obtained before and after 6 months of PRP intra-articular injection. RESULTS: MeHb formation was completely impaired either by of PPP, PRP or albumin indicating that PRP exerts an anti-oxidative effect, probably due by plasma albumin. Analysis of SF samples revealed the presence of MeHb levels and haemosiderin-laden macrophages in SF obtained before PRP treatment. Reduction of synovial MeHb, normalization of cellular composition and improvement of health joint haemophilic score, pain and bleeding episodes were registered after 6 months of PRP intra-articular injection. CONCLUSION: Inhibition of Fenton reaction and the consequent normalization of joint cellular composition is a noncanonical mechanism underlying the therapeutic effect of PRP intra-articular injection in CHS.

Joint lavage followed by viscosupplementation and triamcinolone in patients with severe haemophilic arthropathy: objective functional results.

INTRODUCTION: Viscosupplementation can improve function in haemophilia patients. Viscosupplementation results can be improved by prior joint lavage and triamcinolone administration. AIM: To objectively assess whether viscosupplementation and associated triamcinolone use in patients with severe haemophilic arthropathy following joint lavage improves force and balance and reduces bleeding events. METHODS: Fourteen patients with haemophilic knee arthritis with and without the involvement of other joints underwent joint lavage and subsequent injections of Hylan G-F20 and triamcinolone into all affected joints. Patients were evaluated with NeuroCom® force and balance platforms using the step-up-and-over task (STP), sit-to-stand test (STS), one-leg stance (UNI) and weight-bearing squat (WBS) at baseline and at 1, 3, 6 and 12 months after the procedure. Bleeding events in the year prior to and the year after the procedure were analysed. RESULTS: Sixteen knees, 15 ankles, eight elbows and one shoulder were treated. The STP results indicated improvements in the lift-up indices (right leg) at all time points evaluated (P = 0.03). The STS results revealed coupled improvement in weight transfer and the rising index for up to a year (P = 0.02). Balance (UNI) with eyes open or closed improved in all evaluations. The WBS results revealed improvements at all degrees of flexion (0, P = 0.003; 30°, P = 0.001; 60°, P < 0.001 and 90°, P < 0.001). The numbers of total and traumatic bleeding events were reduced (P = 0.04). CONCLUSION: Joint lavage followed by injections of triamcinolone and Hylan G-F20 improved balance, function and bleeding events in severe haemophilic arthropathy patients.

The effects of repetitive haemarthrosis on postural balance in children with haemophilia.

Sensory information from visual, vestibular and proprioceptive systems is necessary to control posture and balance. Impairment in proprioception due to repetitive joints bleeding may lead to a deficit in postural balance which, in turn, leads to high joint stress and risk of bleeding recurrence. Despite the increase in attention in this field during the past few years, the data concerning to how bleeds can affect postural control in children with haemophilia (CWH) remain scarce. This study aimed to evaluate the postural balance in CWH. Twenty CWH Haemophilia Group (HG) and 20 age-matched children Control Group (CG) were recruited to this study. A force plate was used to record centre of pressure (COP) displacement under four different postural conditions during quiet standing: eyes open on firm surface, eyes open on foam surface, eyes closed on firm surface and eyes closed on a foam surface. Variables of COP as sway area and mean velocity and in anterior-posterior (y) medio-lateral (x) direction were processed and for each variable sensory, quotients were calculated and compared between groups. No differences were found in visual and vestibular quotients variables between groups. A higher value was found in sway area variable on proprioception quotient in the HG when compared with CG (P = 0.042). CWH with repetitive joint bleed on lower limbs showed differences in postural balance when compared with non-haemophiliac children. The identification of early balance impairments in CWH can help us understand better the effects of bleeds inside joints on postural control and plan a more effective preventive and rehabilitative treatment.

9°Yttrium-hydroxyapatite: a new therapeutic option for radioactive synovectomy in haemophilic synovitis.

Recurrent haemarthroses often lead to chronic synovitis in patients with haemophilia and von Willebrand disease. Radioactive synovectomy with yttrium-90 (9°Y) citrate is frequently used to treat this complication, usually with good results. Since 2006, the Nuclear Energy Research Institute (IPEN, Sao Paulo, Brazil) has produced hydroxyapatite particles labelled with 9°Y for radioactive synovectomy. The aim of this study was to compare the results achieved by both forms of 9°Y in the treatment of haemophilic synovitis. We included 221 joints from 136 patients (age range: 6-20 years), treated by one of the two radiopharmaceuticals, at the Hemocenter of Mato Grosso, Brazil. The outcomes analysed were the annual frequency of haemarthrosis, articular pain and joint range of motion before and 1 year after RS. Similar results were achieved regardless of whether 9°Y hydroxyapatite or 9°Y citrate was used, and results were independent of the joint type, age, gender, radiologic stage and presence of inhibitors. 9°Y hydroxyapatite appears to be equivalent to the reference product 9°Y citrate in the treatment of chronic synovitis associated with bleeding disorders.

Radioactive synovectomy with Yttrium9° citrate in haemophilic synovitis: Brazilian experience.

Recurrent haemarthroses leading to chronic synovitis and arthropathy remain a major cause of morbidity in patients with haemophilia. Radioactive synovectomy (RS) is considered the first choice of treatment for chronic haemophilic synovitis. The aim of this study was to evaluate the effect of RS with Yttrium(90) citrate (C-Y(90)) in the joints of patients with chronic haemophilic synovitis. From 2003 to 2007, 245 joints (118 knees, 76 elbows, 49 ankles and two shoulders) of 190 patients with haemophilia or von Willebrand disease were submitted to RS with C-Y(90) at Hemocentro de Mato Grosso, Brazil. Forty joints had radiographic Pettersson scores above 8. There were 36 joints of 22 patients with inhibitors to factor VIII. The procedure was safe with low occurrence of adverse events. The main effect was the overall reduction in joint bleeding frequency, from 19.8 to 2.6 per year post-RS. Similar results were obtained in cases with high radiographic scores and in inhibitor patients. Pain reduction was observed in most cases. Average range of motion was maintained or increased 1 year post-RS in most joints. Extension was stable or increased in 88.2% of the knees and 86.5% of the elbows. Ankle plantarflexion was stable or increased in 90.9%, whereas dorsiflexion was maintained or increased in 87.9%. Worsening of the range of motion, when present, ranged from 14 to 17 degrees. We concluded that RS with C-Y(90) represents an important resource for the treatment of chronic haemophilic synovitis, markedly reducing joint bleeding frequency and pain, irrespective of the radiographic stage and inhibitor status.

Tissue engineering in musculoskeletal problems related to haemophilia.

This article is a review of how advances in tissue engineering can be applied to the musculoskeletal pathology of patients with haemophilia. This article will also explain the theory that the deterioration of joints in patients with haemophilia is due to biological and mechanical causes. Current concepts of tissue engineering would be to replace the degenerated and damaged tissue by live cells, using them as a biological implant. However, before these new technologies are applied, an appropriate control of their indication and results is required.

Computerized pedobarography in the characterization of ankle-foot instabilities of haemophilic patients.

Among the most common clinical manifestations of haemophilia are joint haemorrhages. This study aimed to verify whether repetitive ankle haemarthrosis is associated with instability of the rear foot. We evaluated haemophilic patients with repetitive bleeding in the ankles, 39 of type A and four of type B, whose mean age was 16.1 years. All presented a functional gait, without the need for motion assistance devices. The number of rear-foot and ankle haemarthrosis episodes during the 6 months prior to the study was verified from the medical records of each patient. After verifying the alignment of the rear foot of the patients, we evaluated the subjects through computerized pedobarography with the f-scan system, emphasizing the study of the trajectory of the centre of pressure (COP) with each step taken. All patients received functional orthoses according to the results of these examinations, and were re-evaluated 1 week and 6 months after being fitted. The number of haemarthrosis episodes at the rear foot and the ankle was compared with the occurrence of joint bleeding within the previous 6 months. In the first examination, the COP trajectory showed that all the 43 patients studied had some sort of instability. Six months later, a significant reduction in the frequency of spontaneous bleeding events (P<0.001) concerning the rear foot and the ankle was observed. This method of evaluation was useful to identify joint instabilities, allowing the best prescription of orthoses to improve stability in the rear foot and the ankle.

Sangramientos más frecuentes en los primeros 30 meses de vida de los hemofílicos / Most frequent bleeding disorders in hemophiliacs in the first 30 months of life

La edad pediátrica del hemofílico constituye uno de los períodos más importantes en su vida, pues permite, en cierta medida, predecir la evolución de la enfermedad. En esta edad comienzan los sangramientos y las primeras hemartrosis. En el presente estudio, de 65 enfermos evaluados, 55 (84,6 por ciento) presentaron estas manifestaciones en los primeros 30 meses de edad. Los hematomas aparecieron más precozmente generalmente antes del año, pero el sangramiento articular o muscular ocurrió cuando el niño empezó a caminar(AU)

Chemical synoviorthesis with rifampicin in haemophilia.

Rifampicin is an antibiotic that has been currently used for the treatment of noninfectious articular lesions with satisfactory results. The first experience was performed with patients who presented rheumatoid arthritis, and later with haemophilic patients. The clinical experience of three haemophilia centres which used rifampicin for the treatment of chronic haemophilic synovitis is presented here. The protocols were different. It was observed that rifampicin is more effective when it is used in small joints (elbows and ankles), than when used in bigger ones (knees), and that a high number of injections predicts failure. Mention is also made of experimental studies in animals where it was shown that the healing pattern of rifampicin is similar to that of NSAIDs.

On the safety of synoviorthesis in haemophilia.

One of the best procedures to prevent haem-arthrosis has been radioactive synovectomy (synoviorthesis). Since the first report of radioactive synovectomy in haemophilia of Ahlberg in 1971 [1], many centres adopted this procedure as the one of choice, through fibrosing the synovial membrane, prevent further haemarthrosis. Since 1976 we have performed 104 such radioactive synoviorthesis in 97 patients, age ranging from 6 to 40 years with a mean of 10 years. Sixty-five of these patients were under 12 years of age. The knees were injected in 61 cases, elbow in 26 cases, ankles in 14 cases and shoulders in three cases. The clinical results of this procedure show 80% of excellent results with no further bleeding. In case of failure, a new injection can be given in the same joint at a 6-month interval, or an injection for the same purpose in other joint. One of the criticisms against this method is the possible chromosomal damage induced by the radioactive material. In our centre, four studies have been carried out in order to see whether these changes, when they occur, are everlasting; all have demonstrated that chromosomal changes are reversible. The radioactive material used in the two first studies was Gold-189 (189Au). In 1978, 354 metaphases were studied with 61 ruptures, 17.23% (nonpremalign) and six structural changes, considered premalign (1.69%). Any number below 2% is considered not to be dangerous. A further study was done in 1982, in the same group of patients with a result of 21 ruptures (3.34%) and no structural changes. This demonstrated that the possible premalign changes disappeared with time. A third study was performed in a series of 13 patients that sustained radioactive synoviorthesis with Rhenium-186 (186Re) in November 1991. For comparison, we carried out a chromosomal study just before and 6 months after the radioactive material injection. The results confirmed that changes that could be linked to the radiation, appeared equally in nonirradiated patients, and those changes due to the radiation disappear with time, never reaching the dangerous zone of 2%. In the group treated with 186Re we studied an additional number of 130 metaphases with identical results and no structural changes. In a study on patients where 90Y was the radiocolloid, no premalign change was found before or after the synoviorthesis. It seems, in view of these results, that radioactive synovectomy is safe and gives great benefits to the haemophilic patients.

Artropatía hemofílica: resultados obtenidos con tratamiento de rehabilitación / Haemophilic artropathy: results obtained with rahabilitation

Estudio retrospectivo, longitudinal, descriptivo y observacional, en el que se describen los resultados obtenidos en pacientes con artropatía hemofílica, con tratamiento de rehabilitación preventivo, curativo y asociado al tratamiento quirúrgico. Los pacientes fueron tratados en el servicio de Medicina de Rehabilitación del INP, captados en un periodo de 18 años. En los resultados se aprecia que la prevención fue eficaz para evitar nuevas hemartrosis, así como mejoría en el daño articular causado por hemartrosis aguda y subaguda con tratamiento de rehabilitación curativa, aun con inicio tardío. Las recidivas de deformidad y disfunción articular son casi siempre por nuevas hemartrosis. Los resultados en pacientes con tratamiento de rehabilitación periquirúrgico no fueron concluyentes

Artropatia hemofílica: incidência, importância e reabilitaçäo / Hemophilic arthropathy: incidence, importance and rehabilitation

O estudo de 120 pacientes hemofílicos A e B mostrou a frequência das hemorragias e articulaçöes mais comprometidas. A avaliaçäo articular mostra a perda funcional precoce que ocorre nestes pacientes. A abordagem multidisciplinar pode ser um auxílio importante na prevençäo de sequelas incapacitantes

[Cause of arthritis in childhood. Relation to age, sex and affected joints]. / Causas de artritis en la infancia. Relación con la edad, sexo y articulaciones afectadas.

In a retrospective study (1963--1976) out of 514 children with the general diagnosis of arthritis, the diagnoses most frequently established were; pyogenic arthritis (45.9%), rheumatic fever (18.7%) and juvenile rheumatoid arthritis (17%). Less frequent were tuberculous arthritis (5.8%), systemic lupus erythematosus (3.9%), hemophilic hemarthrosis (2.1%), and other connective tissue diseases (1.5%). Age of onset was significantly lower in patients with pyogenic arthritis. Pyogenic, tuberculous and hemophilic arthritis in most cases were characterized by large joint monoarthritis. Acute polyarthritis was common in rheumatic fever. Chronic polyarthritis was a frequent feature in the other cases. It is concluded that age of onset, number and site of affected joints, as well as evolution time may be useful in the diagnosis.