Aspects of current management: orthopaedic surgery in haemophilia

Summary. If continuous prophylaxis is not feasible due to expense or lack of venous access, we must aggressively treat major haemarthroses (including arthrocentesis) to prevent progression to synovitis, recurrent joint bleeds, and ultimately end‐stage osteoarthritis (haemophilic arthropathy). For the treatment of chronic haemophilic synovitis, radiosynovectomy should always be indicated as the first procedure. If, after three procedures with 6‐month interval, radiosynovectomy fails, an arthroscopic synovectomy must be indicated. Between the second and fourth decades, many haemophilic patients develop joint destruction (arthropathy). At this stage possible treatments include alignment osteotomy, arthroscopic joint debridement, arthrodesis (joint fusion) and total joint arthroplasty. For the hip press‐fit uncemented components (hemispherical acetabulum, flanged femoral stem, metal‐to‐polyethylene) are recommended whilst for the knee a posterior‐stabilized (PS) cemented design is advised. Muscular problems must not be underestimated in haemophilia due to their risk of developing compartment syndromes (which will require surgical decompression) and pseudotumours (which will require surgical removal or percutaneous treatment). Regarding patients with inhibitors, the advent of APCCs and rFVIIa has made major orthopaedic surgery possible, leading to an improved quality of life for haemophilia patients. Concerning local fibrin seal, it is not always necessary to achieve haemostasis in all surgical procedures performed in persons with haemophilia. However, it could be a good adjunct therapy, mainly when a surgical field potentially will bleed more than expected (i.e. patients with inhibitors), and also in some orthopaedic procedures (mainly the surgical removal of pseudotumours).     

The role of physiotherapy after total knee arthroplasty in patients with haemophilia

Summary. With the availability of clotting factor concentrates, advances in surgical techniques, better implant design, and improvements in postoperative management, total knee arthroplasty has become the treatment of choice for haemophilia patients suffering from end‐stage haemophilic knee arthropathy. The success of this surgery is also dependent on close collaborations among the orthopaedic surgeon, the haematologist and the physiotherapist. Although haemophilic patients undergoing this surgery would likely benefit from a targeted rehabilitation programme, its specificities, modalities and limitations have thus far not been extensively studied. Employing the published data of rehabilitation after knee prosthesis in patients with osteoarthritis and haemophilic arthropathy along with clinical experience, the authors present a comprehensive and original review of the role of physiotherapy for patients with haemophilia undergoing knee arthroplasty.     

Haemophilic cysts (pseudotumours)

It is very likely that with the advent of widespread maintenance therapy, pseudotumours will be less common in the future. It is important that they are diagnosed early, and prevention of muscular haematomas is the key to reducing their incidence. There are a number of therapeutic alternatives for this dangerous condition: surgical removal, percutaneous management, exeresis and filling of the dead cavity, irradiation, and embolization. The management of a patient with a haemophilic pseudotumour is complex, with a high rate of potential complications. Surgical excision is the treatment of choice but should only be carried out in major haemophilia centres by a multidisciplinary surgical team. The main postoperative complications are death, infection, fistulization, and pathological fractures (even requiring amputations of affected limbs). Pelvic pseudotumours can even become complicated by fistulization to the large bowel and by obstruction of the ureters. Untreated, proximal pseudotumours will ultimately destroy soft tissues, erode bone, and may produce neurovascular complications.     

Clinical features and management of haemophilic pseudotumours: a single US centre experience over a 30‐year period

Given the rarity of haemophilic pseudotumours, consensus on management is lacking. We describe the clinical features and management of haemophilic pseudotumours by retrospectively reviewing the medical records of haemophilia patients with a diagnosis of pseudotumour seen at our Hemophilia Center from 1981 to 2011. We recorded the following data: type and severity of haemophilia, documented aetiological antecedent, localization of the pseudotumour, presenting symptoms, management and outcome. We identified 12 pseudotumours in 11 patients over a 30‐year period. Six patients had known inhibitors or a history of inhibitor. An aetiological antecedent leading to the development of pseudotumour was reported in nine cases. Localization of the pseudotumour was confined to soft tissue (n = 3) and bone (n = 8). Six of the 12 pseudotumours (50%) were not diagnosed at the time of initial presentation, with a delay ranging from 6 weeks to 6 years. In eight cases, surgical intervention (surgical drainage, n = 2; excision, n = 4; limb amputation, n = 2) was the initial treatment choice, with complete resolution in six cases. Conservative management with close monitoring occurred in three cases, with one case subsequently requiring surgical resection. We conclude that haemophilic pseudotumours still occur sporadically, and the diagnosis is frequently delayed. Surgical intervention is generally a safe and effective treatment, although conservative management may be appropriate in selected cases.     

Viscosupplementation in haemophilic arthropathy: a long-term follow-up study

Haemophilic arthropathy is the most common clinical manifestation of haemophilia, secondary to recurrent haemarthroses and chronic synovitis. Modern bleeding-preventing drugs have limited significantly the incidence of severe arthropathy, and primary approach is usually conservative. Use of intra-articular injections of hyaluronan acid is considered one of the most efficient treatments for early stages of articular degenerative diseases. Assessment of long-term effectiveness of intra-articular administration of hyaluronic acid (HA) in knees, ankles and elbows of patients affected by haemophilic arthropathy was done for 46 patients (10 elbows, 24 knees and 25 ankles) affected by haemophilic arthropathy. They received injections of HA and were evaluated with Visual Analogue Scale, Short Form-36, World Federation of Haemophilia score and Petterson score with a 6-year mean follow-up. Most of the patients showed improvement in pain relief and functional recovery without any complications: only a limited number of patients (8.6%) found poor results, undergoing surgery or other further treatments in the follow-up period for persistent pain or limitation. Viscosupplementation is an effective therapeutic strategy in early stages of haemophilic arthropathy, with no complications and long-term good clinical results.     

Is joint effusion on MRI specific for haemophilia?

Magnetic resonance imaging (MRI) scores for haemophilic arthropathy are useful for evaluation of early and moderate arthropathy. The most recent additive International Prophylaxis Study Group (IPSG) MRI scale for haemophilic arthropathy includes joint effusion. However, it is unknown whether joint effusion is haemophilia specific. Correct interpretation of joint effusion is needed for outcome assessment of prophylactic therapies in haemophilia care. The aim of this study was to compare joint effusion on MRI between young adults with haemophilia and healthy controls. MRI's of both knees and ankles of 26 haemophilic patients (104 joints) and 30 healthy active men (120 joints) were assessed. Scans in both groups were performed in 2009/2010 and 2012 respectively. Joint effusion was measured and scored according to the MRI atlas referred by the IPSG MRI scale for haemophilic arthropathy. Median age of haemophilic patients and healthy controls was 21 and 24 years respectively. In haemophilic patients 23% of knees and 22% of ankles showed joint effusion. Healthy controls had significantly more positive scores for knee effusion (67%, P < 0.01) and a comparable scores for effusion in the ankle (17%). Joint effusion according to criteria of the IPSG MRI scale was observed significantly more often in knees of healthy controls, while findings in ankles were similar. These data suggest that joint effusion in knees and ankles is not haemophilia specific. Inclusion of joint effusion in the MRI scale is expected to reduce its specificity for haemophilic arthropathy.     

The haemophilic pseudotumour

The management of the patient with a haemophilic pseudotumour is complex and carries a high rate of potential complications. There are a number of therapeutic alternatives for this dangerous condition: embolization, radiation, percutaneous management, surgical removal and exeresis, and filling of the dead cavity. It is hoped that with the advent of widespread maintenance therapy, pseudotumours will be less common in the future. It is important that they are diagnosed early, and prevention of muscular haematomas is key to reducing their incidence. Untreated, proximal pseudotumours will ultimately destroy soft tissues, erode bone and may produce neurovascular complications. Surgical excision is the treatment of choice but should only be carried out in major haemophilia centres by a multidisciplinary surgical team.     

Orthopaedic surgery of haemophilia in the 21st century: an overview

Close co-operation between haematologists, orthopaedic surgeons, rehabilitation physicians and physiotherapists is essential for obtaining satisfactory results after orthopaedic procedures that are performed on haemophilic patients. Although continuous prophylaxis could avoid the development of the orthopaedic complications of haemophilia that we still see in the 21st century, such a goal has not been achieved so far, not even in developed countries. Therefore, orthopaedic surgeons are still required to carry out many different surgical procedures, such as arthrocentesis, synoviorthesis, synovectomies, tendon lengthening, articular debridements, alignment osteotomies, joint arthroplasties, nerve releases, opening of compartment syndromes, removal of pseudotumours and osteosynthesis of fractures. Furthermore, the emergence of human immunodeficiency virus has meant that immunosuppressed patients in developed countries sometimes require an arthrotomy for the treatment of spontaneous septic arthritis, or the surgical drainage of a spontaneously infected haematoma (abscess). In addition, they have a high risk of postoperative infection after any surgical procedure, particularly a joint arthroplasty.     

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.     

Management of haemophilic pseudotumours with special emphasis on radiotherapy and arterial embolization

Summary.  The haemophilic pseudotumour is an expanding destructive haematoma, which is associated with a considerable amount of morbidity in haemophilic patients. Its prevention is paramount. In fact, this goal can be achieved by primary prophylaxis to avoid muscle haematomas and by adequate and long-term haematological treatment of muscle haematomas in case they appear. At the moment, surgical excision of pseudotumour is the preferred treatment by many authors. However, there are instances that surgical extraction of the lesion is not feasible. In such situations, radiotherapy and arterial embolization should be considered either alone or as an adjunct to surgery. Conservative management using a combination of radiotherapy and replacement therapy should be considered for treating haemophilic bone pseudotumours, which are located in the skull or in the distal parts of the limbs, especially in conditions where some impediments to surgical excision exist. In fact, the radiation should be delivered to the lesion site in small fragments of 2 Gy or less to a total dosage of 6–23.5 Gy, which is the most recommended radiation dosage, at the moment. Therapeutic arterial embolization of haemophilic pseudotumours should be considered in lesions of large size, especially in pseudotumours of pelvic region, as it may effectively reduce its size and decrease the risk of bleeding complications during surgery. Nevertheless, in view of its temporary effect, embolization may better be performed, as a preparatory procedure, at best about 2 weeks prior to surgery. This time lapse will allow for mass shrinkage but is insufficient for vessel restoration.     

Outcome of surgical concepts in haemophilic arthropathy of the hindfoot

The ankle is one of the most frequent joint affected by haemophilia, in the second decade of life it can be considered as the most common site for haemophilic arthropathy. The aim of this study is to evaluate the results of 15 surgical interventions of the hindfoot performed on 11 patients. Twenty-seven of 70 male patients suffering from haemophilia were treated for haemophilic arthropathy of the hindfoot. We performed 15 operations on 11 patients with a mean age of 33.5 (range: 10-53) years. The surgical treatment consisted of 15 operations, 12 of which concerned the talocrural joint (six synovectomies, three radiosynoviorthesis, four arthrodeses, one achilles tendon lengthening) and one the talocalcaneonavicular joint (one triplearthrodesis). The arthrodeses of the talocrural joint were undertaken by screw, the triplearthrodesis by clamp fixation. The synovectomies were all late synovectomies and performed by open means. The mean follow-up period was 32.0 (range: 12-84) months. The mean age at surgery was 29.6 (range: 8-51) years. No perioperative complications were registered when adequate replacement therapy was carried out. The consolidation of the arthrodeses was accomplished within 8-12 weeks. All synovectomies stopped or reduced significantly recurrent joint bleeding. With both procedures we achieved pain relief and walking ability improvement. The aim of synovectomy is to reduce bleeding episodes. If synovectomy can halt the progression of the haemophilic arthropathy is controversially discussed, especially when surgery was carried out in the presence of an established arthropathy. If synovectomy fails, the arthrodesis proves to be a good treatment option.     

Knee flexion contracture in haemophilia: treatment with circular external fixator

Haemophilia, a bleeding disorder, causes recurrent intra‐articular bleeding of the joints result‐ing in chronic haemophilic arthropathy with fixed knee flexion deformity. Mid‐long‐term results (between 2002 and 2006) of deformity correction in haemophilic patients with Ilizarov type circular external fixators were retrospectively evaluated. There were six patients (five haemophilia A and one haemophilia B). The mean age was 14.7 years (range, 8–22 years) at the time of initial surgery. The mean knee flexion contracture was 45 degrees (range, 30–75 degrees). The mean arc of motion was 58.3 degrees (range, 40–100) before the surgery. The mean duration of follow‐up was 8 years (range, 5.5–10 years). The mean duration of external fixation was 4.4 months (range, 2.5–10.5 months). Full extension of the knee joint was obtained in all patients in the early postoperative period. No bleeding, neurological or vascular complications were encountered. The mean amount of recurrence in knee flexion contracture was 10 degrees (range, 0–15 degrees). The amount of the correction was significant (P = 0.0012) and the mean arc of motion was 51.6 degrees (range, 25–90 degrees) that show a decrease of 6.7 degrees (P = 0.04) at the end of follow‐up. The circular external fixator is an important, safe and less invasive alternative surgical treatment modality with low recurrence rate. Using the external hinges and distraction during the correction has a protective effect on the joint. It requires a team‐work consisting of a haematologist, an orthopaedic surgeon and a physical therapist.     

External fixators for open fractures of tibia and fibula in patients with haemophilia A

To evaluate the efficacy of external fixators(EFs) for management of open fractures of tibia and fibula in patients with haemophilia A. EFs are commonly used in the clinical management of infec‐ted or open fractures when internal fixation is contraindicated and plaster immobilization is inadequate. However, EFs have not been frequently used for these indications in haemophilic patients for fear of pin tract infection and bleeding. This is a retrospective therapeutic study. We describe the use of EF (Orthofix uniplanar fixators) in five patients (mean age: 31.4 years; range: 10–52) with haemophilia A suffering from open fracture of tibia and fibula (Gustilo classification ranging from II to IIIA). The average time to union was 23 weeks (range: 18–30 weeks). Much lower levels were subsequently maintained till wound healing. The average total factor consumption was 358.30 IU kg^?1 (range: 272–421 IU kg^?1), administered over a period of 14.2 days (range 9–21). There were no major complications related to EF. In summary, EFs can be used safely and effectively in management of open fractures of tibia and fibula in patients with haemophilia A.     

Registry of inherited bleeding disorders in Poland – current status and potential role of the HemoRec database

Summary. We present data collected in HemoRec, an Internet‐based platform implemented in 2006 in 15 haemophilia treatment centres in Poland and compare them with the national registry of inherited bleeding disorders established since 1991 at the Institute of Haematology and Blood Transfusion in Warsaw. We also analyse the current status of haemophilia treatment in Poland as well as future perspectives. Data on 1102 patients registered in HemoRec were analysed and compared with 4294 patients in the national registry (status as at 17.08.2009). The number of patients with severe haemophilia, mild/moderate haemophilia and von Willebrand in HemoRec is 530, 328 and 54 (respectively), compared with 1199, 1167 and 1128 in the national registry. The mean age of all haemophilic patients registered in HemoRec is 26.2 years, compared with 37.3 years in the general Polish male population in 2008. The number of haemophilic patients with inhibitor registered in HemoRec is 102 compared with 155 in the national registry (resulting in a prevalence of 14.9% of all severe haemophilia A and 1.6% of all severe haemophilia B patients). HemoRec includes data on a representative group of Polish haemophilic patients, mostly with haemophilia and haemophilia with inhibitor. von Willebrand’s disease is largely under‐registered in Poland. The survival of Polish haemophilic patients is shorter than that in the general population. The number of inhibitor patients in Poland is relatively large and should be decreased by wider availability of immunotolerance induction in 2010.     

Synovectomy for haemophilic arthropathy: 6–21 years of follow-up in 16 patients

Abstract. Objectives . To assess the efficacy of synovectomy in reducing recurrent haemarthroses and joint pain in patients suffering from haemophilic arthropathy. Moreover, to study whether synovectomy could improve joint mobility or postpone progression of joint destruction. Design . A retrospective study was conducted addressing joint-related symptoms and findings, and the need of orthopaedic surgery during follow-up. Setting . Oslo Sanitetsforenings Rheumatism Hospital/The National Hospital, the National Centre for Orthopaedic Surgery for approximately 180 Norwegians suffering from severe congenital coagulation deficiencies. Subjects . Twelve patients with haemophilia A, two patients with von Willebrand's disease and two patients with factor VII deficiency in which 21 synovectomies (nine knees. six ankles and six elbows) were performed. Main outcome measures . Joint pain, joint mobility, frequency of haemarthroses and radiographic joint scores at follow-up were compared to preoperative figures, and the number of joints in need of total joint replacement or arthrodesis was evaluated. Results . Synovectomy proved efficacious in reducing recurrent haemarthroses and joint pain in all patients. The total range of motion was not improved, but correction of extension deficiency of the knee was accomplished. The progression of arthropathy was not arrested by synovectomy as judged by the radiographic assessment; and in four patients arthroplasty of the knee, and in two patients arthrodesis of the ankle, had been performed. A major wound haemorrhage and subsequent wound rupture was seen in one patient who developed high-titred neutralizing antibodies to factor VIII. Conclusions . Synovectomy for haemophilic arthropathy is safe and efficacious in reducing recurrent haemarthroses and joint pain. Synovectomy should not be performed to improve joint mobility. The progression of the arthropathy is not arrested, and subsequently many patients will be candidates for arthroplasty or arthrodesis.     

The effectiveness of radioisotope synovectomy for chronic synovitis in Turkish paediatric haemophiliacs: Ankara experience

Summary. Between January 2006 and December 2009, 37 radioisotope synovectomy (RS) in 18 severe haemophilic patients (factor 8 < 1%) have been performed at our centre. The distribution of joint injected was as follows: rhenium‐186 [Re186], 19 joints (ankles, 8 and elbows, 11) and yttrium‐90 [Y90] 18 joints (knees, 18). Their mean age was 12 years (range: 8–20 years). Mean follow‐up period after procedure was 22.6 months. We preferred to use Y90 for all large joints and Re186 for small joints. Haemophilic patients with grade‐II or III synovitis were selected for RS in our study. Radioisotope synovectomy was performed in eight ankles for seven patients, 11 elbows for seven patients and 18 knees for 13 patients. Mean bleeding counts before the procedure and after the procedure were as follows: Ankles, 3.43 vs. 0.62 (P = 0.002); elbows, 3.12 vs. 0.55 (P = 0.000); and 3.83 vs. 0.62 (P = 0.011). No major complications requiring secondary treatments were observed. In summary, an early RS is the best way to halt the evolution of chronic haemophilia synovitis to devastating haemophilic arthropathy. Radioisotope synovectomy is very effective and safe in the treatment of chronic synovitis of children with haemophilia. Our data confirm the efficacy of RS for the treatment of chronic haemophilic synovitis, which has been previously published by many authors around the world. We highly recommend this procedure for developing countries to prevent joint disabilities. For a better and a healthier generation, RS has to be introduced in all the developing countries.     

Haemophilic magnetic resonance imaging score in healthy controls playing sports

Magnetic resonance imaging (MRI) is the most sensitive imaging modality to assess joint lesions, but the clinical relevance of subtle joint changes in haemophilic patients playing sports is unknown. A haemophilia specific MRI score is available, but was never evaluated in physically active healthy controls. It is not known if unexpected MRI changes in young active haemophilic patients are due to sports participation. The aim of this study was to evaluate knees and ankles in a cohort of young active healthy men using a haemophilia specific MRI score to provide context for joint evaluation by MRI in young haemophilic patients. Three Tesla MRI of knees and ankles were performed in 30 healthy men aged 18–26 years, regularly active in sports. MR images were scored by a single independent radiologist, using the International Prophylaxis Study Group additive MRI score. One physiotherapist assessed clinical function using the Haemophilia joint health scores (HJHS). History of complaints or injuries affecting knees and/or ankles, very intensive sports and current sports activities were documented. Median age was 24.3 years (range 19.0–26.4) and median number of sports activities per week was 3 (range 1–4). Six joints (five knees, one ankle) had a history of a sports‐related injury. The median HJHS per joint was 0 out of 20 (range 0–1). All joints had a MRI score of 0. These results suggest that regular sports participation or very low HJHS scores are not associated with haemophilia specific MRI changes in knees and ankles.     

Orthopaedic surgery in haemophilic patients with inhibitors: an overview

Our experience and a review of the literature on inhibitors have shown that, with the availability of recombinant factor VIIa (rFVIIa), haemophilic patients with high inhibitor titres requiring elective orthopaedic surgery can undergo such surgery with a high expectation of success. The advent of rFVIIa has made major elective orthopaedic surgery possible in haemophilic patients with high-titre inhibitors, resulting in an improved quality of life. Recombinant FVIIa appears to be an efficient haemostatic product for surgery in patients suffering from haemophilia A and B with inhibitors. The series of major elective orthopaedic surgical procedures using rFVIIa (n=53) is the largest ever reported in haemophilic patients with inhibitors, despite the long-standing presence of other treatment modalities, such as high-dose human factor VIII (FVIII), porcine FVIII (n=8), and prothrombin complex concentrates/activated prothrombin complex concentrates (n=9). Thorough analysis of each case as part of a multidisciplinary team will allow us to perform elective orthopaedic procedures in patients with inhibitors.     

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.     

Total joint arthroplasty in haemophilia

In severely affected haemophilic patients arthropathy is a common problem which can lead to considerable pain and functional deficit. Surgical management, including total joint arthroplasty, can be undertaken if conservative management fails. A search of the literature showed that a number of studies describing the use of total knee arthroplasty (TKA) and total hip arthroplasty (THA) in haemophilia have been published, whereas shoulder, elbow and ankle arthroplasties are confined to case reports. This paper reviews the functional outcome of arthroplasty in the different joints, the postoperative and long-term complications, and the impact of HIV. Although complications are commonly described and the surgery is technically demanding, the results suggest that arthroplasty, particularly of the hip and knee, can be a valuable option in the management of severe haemophilic arthropathy.