Cubital tunnel syndrome in patients with haemophilia

Summary. Elbow is the second most common joint involved in patients with haemophilia; however, there is little data about the involvement of ulnar nerve at elbow in patients with haemophilic arthropathy. The purpose of this study was to address this problem in the elbow and evaluate the results of anterior subcutaneous transposition of the ulnar nerve in a small group of patients with haemophilia who had been managed in two institutions. Information on six patients who were diagnosed with tardy ulnar nerve palsy in two institutions was retrospectively collected. All patients suffered form severe haemophilia A. Anterior subcutaneous transposition of the ulnar nerve had been performed in all except one. The mean age of the patients at the time of procedure was 45.8 years and the mean duration of follow‐up was 60.2 months. No postoperative complication or recurrence was observed. No additional surgery was required in operated patients. Evaluation was performed using subjective and objective measures, and a modified Bishop score. After operation, subjective sensory and motor disturbances were improved or resolved in all of the operated patients, while objective measures improved less well. Ulnar nerve can be involved in cubital tunnel in patients with haemophilia. Anterior subcutaneous transposition of the ulnar nerve is an effective procedure for improving patients’ symptoms, with low risk of complications.     

The Spectrum of Myositis Ossiticans in Haemophilia

Myositis ossificans (MO) refers to non-neoplastic heterotopic soft tissue ossification that can have several aetiologies. Broadly it can be classified into three categories based on aetiology [1]. MO traumatica, the most common form occurs secondary to acute or chronic trauma. MO can also be associated with neurological disorders and in rare cases is congenital. The latter (progressive MO) is a genetic disorder in which congenital osseous abnormalities are associated with progressive soft tissue calcification. Despite an increased tendency to soft tissue bleeds, MO has been rarely reported in haemophilia. We treated three adolescents with haemophilia and MO of varying degrees of severity and outcome.     

Heterotopic bone formation in rectal carcinoma

A case of heterotopic bone formation in a primary rectal adenocarcinoma was recently observed in a 54-year-old woman. This unusual finding was present both in the diagnostic biopsy and in the subsequently resected bowel. Pertinent gross and microscopic features are presented. This report represents the twelfth case in the literature of heterotopic bone formation in a primary rectal adenocarcinoma and the first such finding in a colonic biopsy from one of these malignancies. The average age of these patients was 56 years (range 32-72) and the male-to-female ratio was 5:7. The rectum is the most common site of ossification in the gastrointestinal tract. The exact mechanism of heterotopic ossification is unknown, but it is probably the result of metaplasia of fibroblasts. Adenocarcinoma has been associated with 12 of the 16 reported cases of rectal glandular tumors with heterotopic bone.     

HISTOCOMPATIBILITY ANTIGENS IN PATIENTS WITH SPINAL CORD INJURY OR CEREBRAL DAMAGE COMPLICATED BY HETEROTOPIC OSSIFICATION

The frequency of HLA antigens of the A and B loci in 21 patientswith spinal cord injury and three patients with cerebral damagecomplicated by heterotopic ossification was compared with thefrequency seen in 740 healthy controls. No significant differencein the frequency of HLA antigens was detected between the twogroups. In contrast to a previous study, when the spinal cord injurypatients complicated by heterotopic ossification were comparedto healthy controls, there was no increase in the frequencyof HLA B18. Further studies of the HLA system in patients withheterotopic ossification are warranted. ^*Presented in part at the Annual Meeting of the Royal Collegeof Physicians and Surgeons of Canada, Vancouver 1978.     

Fibrodysplasia ossificans progressiva without characteristic skeletal anomalies

Fibrodysplasia ossificans progressiva (FOP) is a rare but extremely disabling genetic disease of the skeletal system. This disease is characterized by progression of heterotopic ossification within skeletal muscles, ligaments and tendons. Most patients with FOP are misdiagnosed early in life before the appearance of heterotopic ossification and undergo diagnostic procedures such as biopsy that can cause lifelong disability. Almost all of the patients have some peculiar congenital anomalies, including short great toes, hallux valgus, short thumbs and hypoplasia of digital phalanges. These congenital defects support the diagnosis of FOP, but are not constantly observed in the totality of patients. If necessary, genetic studies can be performed to confirm the diagnosis. Once diagnosed, patients should be advised in order to avoid unnecessary traumas, surgical procedures, biopsies, intramuscular injections and vaccinations. Here, we describe a patient with FOP without characteristic congenital skeletal anomalies.     

Haemophilia in Poland

The primary aim of this study was to analyse the data on 2269 haemophilic patients in the Polish National Register of Inherited Bleeding Disorders -- 1953 haemophilia A patients and 316 haemophilia B patients. Haemophilia A occurred in 1512 families, haemophilia B in 240 families. In the majority of haemophilia A and B cases severe haemophilia prevailed (59.7% and 56.6% respectively). In about 50% of haemophilic patients, no family history of bleeding diathesis was reported. For haemophilia A patients the mean age was 30.9 years and for haemophilia B patients, 29.2 years. Prevalence of haemophilia in Poland is approximately 1:12 300 inhabitants (1:5600 males). The second aim was to describe the orthopaedic status of severe haemophilia patients and to relate this status to the type of replacement therapy they received prior to the study. Ninety-two severe haemophilia patients (median age 26.0 years) were enrolled in the study. Right and left knee, elbow and ankle joints were evaluated clinically using the Gilbert scale. X-ray examinations were evaluated according to the Pettersson scale. Knee joints proved to be most affected. Eighty-four patients (91.3%) reported pain. Only one scored 0 on the Gilbert scale, another on the Pettersson scale. Thirty-seven per cent of patients used orthopaedic equipment, either occasionally or constantly. Twenty-five per cent had a history of orthopaedic surgery. Thirty-eight per cent were unemployed with some form of social subvention. On-demand treatment was applied. None of the patients received primary prophylaxis. The mean consumption of clotting factor concentrates was 68 054 IU per patient during the 12 months prior to the current study. These results indicate that in Poland all severe haemophilia patients above 20 years are affected by haemophilic arthropathy.     

Functional kinesiology in haemophilia, an area yet to be explored

Summary. In haemophilic arthropathy there is a progressive limitation of the range of motion (ROM) which may lead to disabilities in the activities of daily living (ADL). In the literature the pathology of haemophilic arthropathy is described extensively, but only one paper describing functional limitations caused by limited range of motion (LOM) in haemophilia was found. The aim of the pilot study was to estimate on theoretical grounds, how many patients with haemophilia might suffer from functional disabilities. Material: ROM of elbows, knees and ankles of 155 Haemophilia A and B patients. Methods: flexion and extension were measured with an ordinary goniometer. The ROM of joints of patients with haemophilia was compared with normal values. Results: 39 of 155 patients had a normal ROM in both elbows; 22 in one elbow; 34 patients had disabilities in ADL with both arms; 14 with one arm; 18 were able to compensate; 89 had no problems; 79 of 155 patients had a near normal ROM of both knees; 38 patients could not ride an ordinary bicycle. Conclusion: only limited data are available concerning the normal ROM needed for individual ADL. Until additional data are available, it is not possible to predict which patients will be disabled in their activities of daily living and individual counselling should be done during the yearly outpatient comprehensive care clinics. Conservative and surgical measures should be taken to ensure elbow flexion of at least 120° and knee flexion of 100° for Western societies. In Asian countries patients with haemophilia need maximum knee flexion and ankle dorsi flexion.     

Long‐term outcomes in haemophilic synovitis after radiosynovectomy using rhenium‐186: a single‐centre experience

Radiosynovectomy has been performed successfully for more than 10 years in our hospital. This study investigated the long‐term outcome in the context of time to progression (TTP) analysis and the factors influencing TTP following radiosynovectomy with Re‐186 in patients with haemophilic synovitis. Radiosynovectomy performed in 165 joints (81 elbows, 74 ankles, 8 shoulder and 2 hip joints) of 106 patients (median age was 18.0 ± 7.5 years; 91 haemophilia A, 13 haemophilia B and 2 von Willebrand's disease between June 2001 and July 2011. The mean follow‐up was 48 months (range: 9–120 months). This study revealed that patients' mean TTP after primary radiosynovectomy was satisfactory for both the ankle and elbow joints. There was no TTP differences between the ankle and elbow joint groups (67 vs. 72 months respectively; P = 0.22). We did not find a relationship between the TTP and the following variables: age, type and severity of haemophilia, the presence or absence of inhibitor, the radiological score, range of motion (ROM) status of joints and the pretreatment bleeding frequency. In this study, 18–20% of the treated joints had improved ROM and 82–79% of the treated joints had unchanged ROM after treatment both the ankle and elbow joints respectively. In this report including TTP analysis in the largest series with long‐term follow‐up, we demonstrated long‐term effectiveness of Re‐186 radiosynovectomy in haemophilic synovitis. In our experience, the main predictor of outcome following radiosynovectomy is the number of joint bleeding within 6 months after therapy.     

Heterotopic bone formation after joint replacement.

Bone formation outside the skeleton, heterotopic ossification (HO), is a common finding on radiographs from patients who have undergone arthroplasty of the hip, knee, shoulder, or elbow. Only a minority (5%-10%) of the patients with HO suffer from any consequence of the condition. However, because of the great number of joint replacements performed, the number of patients with decreased function that can be attributed to HO is significant. The risk for severe HO after total hip arthroplasty is increased in 1) patients who have developed HO after previous surgery, 2) men with hypertrophic osteoarthrosis and, 3) in patients with ankylosing spondylitis or diffuse idiopathic skeletal hyperostosis. The same risk factors are probably valid for other joints as well. Two preventive treatments for HO after hip arthroplasty, nonsteroidal anti-inflammatory drugs and local radiation, are effective and reasonably well documented but are associated with potential side effects. Thus, a treatment protocol to prevent HO must identify the patients at risk for severe HO and recommend them treatment with one of these two modalities. Based on the current literature, we suggest that the patients at risk for severe HO be treated with 1) nonsteroidal anti-inflammatory drugs from the day of surgery for 7-10 days or 2) preoperative (or postoperative) radiation in a single dose.     

Iliopsoas haemorrhage in patients with haemophilia: results from one centre

Iliopsoas haematoma is a well-recognized complication of haemophilia, and is considered as potentially life threatening and significantly associated with morbidity. There are only rare reports on the incidence or outcomes of iliopsoas bleeding since the widespread usage of modern therapies for haemophilia. In this study, we present the experience of Ege University Haemophilia Centre with iliopsoas bleeding and its early and late complications. We reviewed 146 haemophiliacs (106 haemophilia A, 40 haemophilia B). Fourteen iliopsoas bleeding episodes were identified in eight haemophiliacs. Three patients (37%) had one episode, four (50%) had two episodes and one (13%) had three episodes. Two patients had a high titre inhibitor against factor VIII and accounted for three bleeding episodes (21%). We did not observe any episodes in six patients receiving prophylaxis. Iliopsoas haematomas were confirmed by ultrasonography in all patients. In physical examination, the most common symptoms were thigh, hip and groin pain, hip flexion contracture, abdominal tenderness and paraesthesia in the distribution of the femoral nerve. The mean duration of therapy with clotting factor concentrate was 7.8 +/- 1.6 days. The mean duration of hospitalization was 4.8 +/- 2.0 days. All patients started to receive a physical therapy program 6.0 +/- 2.4 days after the initiation of haemostatic therapy which lasted 20.0 +/- 6.0 days. Ultrasonographic findings related to iliopsoas haematoma disappeared in all patients within 3 months from the initial episodes. Only in one patient with mild haemophilia A, heterotopic bone formation (myositis ossificans) developed as a long-term complication. In conclusion, pain around the hip joint, femoral neuropathy and hip flexion contracture in a patient with haemophilia should alert the physician to the possibility of an iliopsoas haematoma. Early and effective factor replacement therapy is essential in the prevention of the complications.     

Polyarticular heterotopic ossification complicating critical illness.

A patient with generalized heterotopic ossification (HO) complicating critical illness due to necrotizing pancreatitis is described; data on two other cases with HO are briefly presented. The clinical features, prevention and therapy of HO are discussed. The effect of surgical therapy of the HO in our three patients was good.     

Haemophilic arthropathy of the elbow

Patients affected by haemophilia commonly have recurrent intra-articular bleeding which leads to progressive destruction and instability of joints. Severe arthropathy of the elbow is complicated by pain, stiffness and loss of function which can be debilitating. Conservative measures such as analgesics, physiotherapy and orthotics are commonly used in the management of these patients. Surgery is considered when conservative measures fail to control the symptoms. Total elbow replacement is now increasingly performed with the advances made in factor replacement therapy and evolution of better implants and techniques of total elbow arthroplasty. The pathogenesis, clinical features and radiological changes of haemophilic arthropathy of the elbow are described in this review article.     

Heterotopic mesenteric ossification: a rare cause of postoperative occlusion

Intraabdominal heterotopic ossification is a very rare lesion, especially in the mesentery. In all reported series, there was a history of traumatic injury of the abdomen. We report two cases of heterotopic mesenteric ossification occurring after laparotomy in adults.     

What patient,joint and isotope characteristics influence the response to radiosynovectomy in patients with haemophilia?

Summary. The literature describes radiosynovectomy (RS) as a good non‐surgical option for reducing synovial membrane size and thus the number of haemarthrosis episodes. However, there are still many aspects concerning the beneficial effects of RS that have not been quantified. A total of 156 radiosynovectomies (RS) were performed in 104 joints corresponding to 78 haemophiliacs (yttrium‐90, rhenium‐186). The mean patient age was 18 years. In another study involving the same group of patients, the parameters that improved most after RS were pain and haemarthrosis, followed by the World Federation of Hemophilia clinical score, muscle strength and range of movement (ROM). Following RS, improvement was seen to be independent of patient age, haemophilia type and grade, previous haematological treatment, the presence or absence of circulating inhibitor, synovial membrane size, the type of joint (elbow, knee and ankle), previous physical activity or lack of activity, the prior presence or absence of radiographic signs of joint degeneration (arthropathy) or the isotope used. RS is effective in treating haemophilic synovitis and may require 1–3 injections (RS‐1, RS‐2 and RS‐3) spaced 6 months apart. Following RS‐1, the knee had a 3.4‐ and 3.2‐fold greater risk of not improving in terms of pain, compared with the elbow and ankle, respectively. Regarding ROM, lesser improvement was recorded after RS‐1 in cases of severe haemophilia and the ankle. In other words, severe haemophilia implies a 2.1‐fold greater risk of no improvement in ROM compared with mild and moderate haemophilia. In addition, the ankle presented a 6‐fold greater risk of not improving in terms of ROM compared with the elbow and knee. RS affords effective treatment of chronic haemophilic synovitis. RS is effective in all patient groups, independently of the presence of circulating inhibitor antibody, the type of joint involved, the degree of synovial membrane hypertrophy and the presence of radiographic findings of joint degeneration (arthropathy).     

Early fibrodysplasia ossificans progressiva-like lesion formation in nude mice following implantation of lymphoblastoid cells from FOP patients

Fibrodysplasia ossificans progessiva (FOP) is a genetic disease of progressive, heterotopic ossification, resulting in profound decreased mobility. To investigate the pathophysiology of this condition, lymphoblastoid cells (LCLs) derived from patients with FOP or unaffected family members were implanted subcutaneously into athymic (nude) mice. Cells from unaffected individuals persisted as small masses with little evidence of a fibrotic or angiogenic response. In contrast, cells from patients with FOP gave rise to palpable, solid, fibrotic cellular masses in the animals. Histological and immunohistochemical evaluation revealed that FOP cells proliferated in the host and induced a fibrotic and angiogeneic response similar to the early-stage FOP lesions in patients, but did not progress to form ettopic cartilage or bone. These results de monstrate that lymphoblastoid cells from patients with FOP induce early preosseous FOP-like lesions in mice, but are not sufficient to induce heterotopic ossification in immunocompromised host animals. Implantation of FOP-derived cells in nude mice provides a useful model system for examining the earliest stages of the disease.     

The natural history of mild haemophilia: a 30‐year single centre experience

Summary. Although up to 50% of all haemophilic patients followed at haemophilia treatment centres (HTCs) are affected by a mild factor VIII (FVIII) or factor IX (FIX) defect, published data regarding the natural history of these disorders are scarce. To fill this lack of information, a retrospective single centre study was conducted. All cases with mild haemophilia (75 A and 7 B) followed at the regional reference HTC of Parma were evaluated. The patients’ median age at diagnosis was 11.5 years and their median age at first bleeding was 5.5 years; 95% of patients had a history of haemorrhagic problems during their life. Twenty‐three percent of patients were infected by HCV, and none by HIV. Genetic analysis was performed in 80 patients (97% haemophilia A and 100% haemophilia B) and 21 different mutations were characterized. Eleven percent of patients had never received treatment, whereas 67% were treated with plasma‐derived or recombinant FVIII/FIX concentrates (4% developed inhibitors). desmopressin (DDAVP) was used in 80% of the haemophilia A patients. The response to DDAVP was closely related to the patients’ genetic profile, as 60% of non‐responders had a mutation in the F8 promoter region. Patients with mild haemophilia may experience a variety of medical problems, sometimes challenging for the physicians, during their lifetime. The HTCs play an important role in the management of these patients, whose diagnosis is often delayed. The HTCs should improve patients’ knowledge and consideration of their disease and encourage them to maintain regular contact with their haemophilia care provider.     

Orthoses in haemophilia

In haemophilia patients, orthoses are used for the prevention and management of bleeds and their effects on the musculoskeletal system. The characteristics of these devices vary according to the joint to which they are applied, although two basic types are distinguished: static and functional. The upper limbs make up a functional unit that is adapted to prehension, or the action of grasping or seizing objects. The most affected joints of this unit in haemophilia are the elbow and shoulder, which require immobilization, followed by stabilization and protection and in the case of disability, assistance in the performance of function. The lower limbs, on the other hand, are adapted to the action of ambulation. The knee, ankle and hip joints frequently sustain damage in haemophilia, and in the acute phase they should be immobilized and the patient discouraged from walking. Once bleeding has ceased, and motion and muscle balance improved, a gradual return to normal activity may commence. The principle aim of orthotics in these cases is to immobilize and unburden the affected body segment, and to provide stability and assistance for ambulation. Shoe insoles cushion and modify stance, and therefore may help prevent lesions. Crutches and walking frames are used for restoring normal gait. Orthotic devices improve the quality of life of haemophilia patients with musculoskeletal lesions and are useful for preventing lesions resulting from strenuous activities, whether performed in the course of daily living or in the pursuit of games and sports.     

Knowledge of disease and adherence in adult patients with haemophilia

Summary. Patients with moderate and severe haemophilia are evaluated on a regular basis at their haemophilia centres but patients with mild haemophilia are seen less often because of fewer problems related to their disease. The needs of patients with milder forms of haemophilia, however, are often underestimated, both by the patient and staff at healthcare facilities. This study evaluated the knowledge of disease and adherence to treatment among patients with severe, moderate and mild haemophilia. This was a prospective multicentre study performed in Haemophilia Centres in Scandinavia. A total of 413 (67%) of 612 patients aged >25 years with mild, moderate and severe haemophilia completed a self‐administered questionnaire. The mean age of the respondents was 49.7 years (range 25–87 years). Of the 413 respondents, 150 had a mild, 86 had a moderate and 177 had a severe form of haemophilia. A total of 22 (5%) patients did not know the severity of their disease, and 230 (56%) patients knew the effect of factor concentrate in the blood. Of the 413 respondents, 53 (13%) of the cohort never treated a haemorrhage. Patients with mild haemophilia, P ≤ 0.001, were the least likely to treat a haemorrhage. The relative number of patients who were afraid of virus transmission by factor concentrate was about similar in the three groups, 27% of those with severe haemophilia, 26% with moderate and 24% with mild haemophilia. This study shows that the amount of knowledge among haemophilia patients about their disease and treatment is somewhat limited, and demonstrates the importance of continually providing information about haemophilia and treatment, especially to patients with a mild form of the disease.     

Ipsilateral total shoulder and elbow prosthetic replacement in a patient with severe haemophilia B

Since factor replacement concentrates became widely available in the 1970s, total prosthetic replacement of joints in haemophilic patients has become increasingly common, with success particularly in the knee and hip. However, there has been no published series of elbow or shoulder replacements large enough to draw conclusions about the advisability of these procedures in this group of patients.
We report a case of prosthetic replacement of the shoulder in a 58-year-old man with haemophilia B, and replacement of the elbow joint of the same limb 21 months later. The results are initially very encouraging, with no pain in either joint since the early post-operative period. There have been no bleeds into either joint since surgery. Ranges of movement are satisfactory. Follow-up is now 37 months for the shoulder and 16 months for the elbow.     

Changing patterns of bleeding in patients with severe haemophilia A

Summary.  Previous studies on the pattern of joint bleeding in patients with haemophilia have reported that the knee joint is most frequently affected. Home treatment data reporting bleeding frequency and location collected from 100 patients registered at six haemophilia centres in the UK have been analysed to determine current patterns of bleeding. Bleeding frequency has markedly decreased although bleeding into joints remains the main characteristic of haemophilia. However, the ankle joint has replaced the knee joint as the most common joint affected. Furthermore, it seems that the frequency of knee joint bleeding is also less than the elbow joint suggesting that the traditional pattern of joint bleeding in haemophilia has now changed significantly.