Bleeding symptoms and laboratory correlation in patients with severe von Willebrand disease

Summary.  Type 3 von Willebrand disease (VWD) is a rare bleeding disorder with markedly decreased or absent von Willebrand factor (VWF) protein, accompanied by a parallel decrease in VWF function and factor VIII (FVIII) activity. The goal of this study was to describe the population of patients enrolled in the USA Centers for Disease Control Universal Data Collection (UDC) study with type 3 VWD, defined as a VWF:Ag of <10%, and to correlate bleeding symptoms with VWF and FVIII levels. Data on 150 patients were analysed. Almost all patients experienced bleeding episodes (98%) and required blood and/or factor product treatment (92%). While oral mucosal bleeding (the site of first bleed in 54%) was most common, subsequent muscle and joint bleeds were also seen (28%, 45%, respectively), and intracranial haemorrhage occurred in 8% of individuals. Mean age of first bleed was lower in those with either a FVIII ≤5% or a VWF:Ag <1%. Univariate marginal model analysis showed lower levels of FVIII and VWF:Ag both predicted a higher risk of joint bleeding. Longitudinal multivariate analysis found a lower FVIII level ( P  = 0.03), increasing age ( P  < 0.0001), history of joint bleeding ( P  = 0.001), higher body mass index (BMI) ( P  < 0.0001), and use of home infusion ( P  = 0.02) were all negatively associated with joint mobility. Low levels of VWF:Ag ( P  = 0.003) and male sex ( P  = 0.007) were also negatively associated with joint function. This study documents the strong bleeding phenotype in severe VWD and provides data to help target therapy, including prophylaxis, for patients most at risk of bleeding complications.     

Clinical evaluation after 1 year of 153-samarium hydroxyapatite synovectomy in patients with haemophilic arthropathy

Summary. The aim is to evaluate the efficiency of the treatment with 153‐samarium hydroxyapatite (153‐Sm‐HA) in haemophilic arthropathy. Thirty‐one patients (30 males) with ages ranging from 8 to 34 years (average age = 20.6 years) were treated with fixed intra‐articular dose of 185 MBq (5 mCi) and divided into two groups: infantile‐juvenile (13 patients with up to 18 years of age, an average age of 12.7 years and arthropathy evolution of 7.8 years), and adult (18 patients older than 18 years, an average age of 24 years and arthropathy evolution of 18.7 years). The clinical evaluation before and after 1 year of synovectomy used the following criteria: subjective (pain through visual scale, articulation inspection), objective (articular movement through flexion level, sensitivity to palpation and leakage through joint circumference), reduction on the use of the coagulation factor, number of haemarthrosis, and the occurrence of adverse effects. The results were classified as: 1, good (remission from 70% to 100% of manifestations); 2, moderate (remission from 40% to 69%); and 3, poor (remission from 0% to 39%). Seventy‐eight joints were tested: 15 knees, 36 elbows, 24 ankles, 1 shoulder and 2 hips. Early scintigraphic (1–2 h) and late scintigraphic (24–72 h) studies were performed after synoviorthesis. The cost of the procedure per joint was also estimated. No significant difference in the synoviorthesis result between groups was observed. The results were good for 75% of elbows, 87.5% of ankles and 40% of knees; the reduction in haemarthrosis and use of the coagulation factor was respectively 78% and 80% for elbows, 82% and 85% for ankles and 30% and 35% for knees. Four cases of reactional synovitis were observed in the 31 patients. The scintigraphic control showed homogeneous distribution of the material with no articular escape. The use of 153 Sm‐HA in the treatment of the haemophilic arthropathy is effective for intermediate‐size joints (elbows and ankles), but less effective for knees. Moreover, this treatment presents an excellent safety profile and accessible cost.     

A case of progressive pseudorheumatoid arthropathy of 'childhood' with the diagnosis delayed to the fifth decade

Progressive pseudorheumatoid arthropathy of childhood (PPAC) is a rare single gene disorder which is frequently misdiagnosed as juvenile rheumatoid arthritis. It is characterised with arthralgia, joint contractures, bony swelling of metacarpophalangeal and interphalangeal joints and platyspondyly. Clinical and laboratory signs of joint inflammation such as synovitis, a high erythrocyte sedimentation rate and an elevated C-reactive protein level are usually absent. Although the disease begins early in life (usually between 3 and 8 years of age), the diagnosis may be delayed. In the present case report, we describe a male patient diagnosed with PPAC at the age of 46 years, although he had been exhibiting the typical radiological and clinical features of the disease since the age of 7 years.     

Functional disability in children with hemophilic arthropathy

Hemophilia is a coagulation disorder characterized by acute hemorrhages into the musculoskeletal system, leading eventually to arthropathy and disability. We investigated the functional loss, namely disability, in hemophiliacs. The clinical and radiological characteristics of joint involvement were also evaluated. There were 31 patients between the ages of 3 and 18 years and 65 involved joints. The knees were the most commonly affected joints followed by the elbows and ankles. There was a positive correlation between the radiological and clinical evaluation scores; however, the clinical evaluation score did not correlate with age. The radiological score increased in conjunction with increasing age of the patients. We observed a significant relationship between the disability score and the clinical evaluation and radiological scores. These observations suggest that hemophilia is a life-long condition, with a high potential for functional disability if not promptly and adequately controlled. The main principle in the treatment of hemophilic arthropathy is the restoration of the patient’s lifestyle and mobility with a comprehensive multidisciplinary approach.     

Mechanical analysis of cuff tear arthropathy during multiplanar elevation with the AnyBody shoulder model

Background

This numerical study analysed the mechanics of cuff tear arthropathy with the AnyBody shoulder model.

Methods

The model simulated three frequent characteristics of cuff tear arthropathy: A supero-posterior massive rotator cuff tear, a proximal and static migration of the humeral head, and a contact between the humeral head and the scapula (glenoid &; acromion) with friction. The mechanics of the cuff tear arthropathy with and without friction were studied by analysing: the mechanics of the deltoid (i.e. length &; strength), the gleno-humeral and acromio-humeral contact forces, the friction moment, and the maximum elevation angle. Elevations in the frontal, scapular and sagittal planes were simulated.

Findings

Compared to an intact condition, the cuff tear arthropathy model without friction estimated a deltoid strength of − 18% (frontal = − 13%, scapular = − 17%, sagittal = − 25%), a gleno-humeral contact force of − 34% (frontal = − 60%, scapular = − 46%, sagittal = + 5%), estimated an acromio-humeral contact force of 240 N (frontal = 213 N, scapular = 184 N, sagittal = 324 N) and a maximum elevation angle of 77° (frontal = 80°, scapular = 87°, sagittal = 65°). Contact friction enhanced this behaviour, decreasing even more the gleno-humeral contact force and the maximum elevation angle, while increasing the acromio-humeral contact force.

Interpretation

This novel cuff tear arthropathy model suggests that friction and plane of elevation greatly influence the mechanics of the shoulder with cuff tear arthropathy. It also shows that the AnyBody simulation tool may be useful to study musculoskeletal pathologies and not only normal conditions.     

A modeling approach to evaluate long-term outcome of prophylactic and on demand treatment strategies for severe hemophilia A

Background

Severe hemophilia requires life-long treatment with expensive clotting factor concentrates; studies comparing effects of different therapeutic strategies over decades are very difficult to perform. A simulation model was developed to evaluate the long-term outcome of on demand, prophylactic and mixed treatment strategies for patients with severe hemophilia A.

Design and Methods

A computer model was developed based on individual patients’ data from a Dutch cohort study in which intermediate dose prophylaxis was used and a French cohort study in which on demand treatment was used, and multivariate regression analyses. This model simulated individual patients’ life expectancy, onset of bleeding, life-time joint bleeds, radiological outcome and concentrate use according to the different treatment strategies.

Results

According to the model, life-time on demand treatment would result in an average of 1,494 joint bleeds during the hemophiliac’s life, and consumption of 4.9 million IU of factor VIII concentrate. In contrast, life-time intermediate dose prophylaxis resulted in a mean of 357 joint bleeds and factor consumption of 8.3 million IU. A multiple switch strategy (between prophylactic and on demand treatment based on bleeding pattern) resulted in a mean number of 395 joint bleeds and factor consumption of 6.6 million IU. The estimated proportion of patients with Pettersson scores over 28 points was 32% for both the prophylactic and the multiple switching strategies, compared to 76% for continuous on demand treatment.

Conclusions

The present model allows evaluation of the impact of various treatment strategies on patients’ joint bleeds and clotting factor consumption. It may be expanded with additional data to allow more precise estimates and include economic evaluations of treatment strategies.     

Anatomic or reverse shoulder arthroplasty: indications and decision-making

Shoulder replacement surgery has become the gold standard treatment for end-stage glenohumeral arthropathies in patients who are fit for surgical treatment. The options include anatomic total shoulder replacement, reverse total shoulder replacement and humeral hemiarthroplasty procedures. Whilst for some patients and some indications there is little debate, decision-making for older patients with osteoarthritis remains one of the hot topics in shoulder surgery. In this article we will explore the treatment options, outcomes, and controversies.