Hemostatic Management in an Infant With Neuroblastoma and Severe Hemophilia B With Extended Half-life Recombinant Factor IX Fusion Protein.

In the rare co-occurrence of childhood cancer and severe hemophilia, hemostatic management is of paramount therapeutic importance. We present the case of an 11-month-old boy with severe congenital hemophilia B, who was diagnosed with metastatic high-risk neuroblastoma. He consequently developed paraneoplastic coagulopathy with life-threatening tumor hemorrhage and intracranial hemorrhage, showing central nervous system relapse. Management consisted of factor IX replacement with extended half-life factor IX fusion protein, adjusted to bleeding risk. Additional interventions included factor XIII, fibrinogen, fresh frozen plasma, tranexamic acid, and platelet transfusions. The half-life of factor IX products was markedly reduced requiring close factor IX monitoring and adequate replacement. This intensified treatment allowed chemotherapy, autologous stem cell transplantation, and GD2 antibody immune therapy without bleeding or thrombosis.

Imaging features of atypical bleeds in young patients with hemophilia.

Hemarthroses and muscle bleeds are well-known and well-documented complications in pediatric and young adult hemophilia patients. In contrast, deep bleeds in atypical locations can be a diagnostic challenge, since clinicians and radiologists are often unfamiliar with their clinical and radiological features. Some atypical bleeds, however, can be life-threatening or severely disabling, highlighting the need for prompt, accurate diagnosis. Rare bleeds include central nervous system bleeds (including intracranial and spinal hematomas), urogenital bleeds, intra-abdominal bleeds (mesenteric and gastrointestinal wall hematomas) and pseudo tumors in unusual locations like the sinonasal cavities. Because clinical assessment can be difficult, clinicians and radiologists should be aware of the possibility of these rare complications in their hemophilia patients, so that they can avoid unnecessary invasive diagnostic and surgical procedures and institute prompt, appropriate treatment. The purpose of this review is to illustrate the imaging features of bleeds that occur in rare locations in young (i.e., children and young adults) patients with hemophilia to make the reader more familiar with these conditions.

Manual therapy in the treatment of patients with hemophilia B and inhibitor.

BACKGROUND: The main clinical manifestations of hemophilia are muscle and joint bleeding. Recurrent bleeding leads to a degenerative process known as hemophilic arthropathy. The development of inhibitors (antibodies against FVIII/FIX concentrates) is the main complication in the treatment of hemophilia. The objective was to assess the safety and efficacy of manual therapy treatment in a patient with hemophilia and inhibitor. CASE PRESENTATION: A 26-year-old patient with hemophilia B and inhibitor received physiotherapy treatment based on manual therapy for 3 months, with a frequency of 2 sessions per week. The joint status was evaluated using the Hemophilia Joint Health Score; pain was assessed with the Visual Analog Scale; and the range of movement was evaluated using a universal goniometer. The patient developed no joint bleeding in the knees or ankles as a result of the physiotherapy treatment. Following treatment, improvements were noted in the range of movement of knees and ankles, the perception of pain in both knees, and ankle functionality. CONCLUSIONS: Until now, manual therapy using joint traction was contraindicated in patients with hemophilia and inhibitor, as it was feared to cause possible joint bleeding. This is the first case study to address the safety and efficacy of manual therapy in a patient with hemophilia and an inhibitor. The results of this study may help to establish which manual therapy treatments are indicated in patients with hemophilic arthropathy and inhibitors. Thus, a physiotherapy program based on manual therapy may be safe in patients with hemophilia and inhibitor and such therapy may improve joint condition, pain, and joint range of motion in patients with hemophilia and inhibitor. Randomized clinical trials are needed to confirm the results of this case study.

Hemophilic pseudotumor of the mandible in a patient with hemophilia B.

INTRODUCTION: Hemophilic pseudotumor is a rare complication occurring in patients with hemophilia, frequently seen in the femur, tibia, pelvic bones, iliac bones, or rarely in the maxillofacial region. CASE REPORT: A 7-year-old male reported with a spontaneous extra-oral swelling that was managed with pre-operative transfusion of factor IX along with curettage of the lesion. Our report presents only the fourth case in literature wherein this tumor presented in a patient with hemophilia B. FINDING: Hemophilic pseudotumor is a rare entity in the maxillofacial region. High degree of suspicion is required for diagnosis, and close coordination between the medical and surgical teams aids in management.

Haemophilic pseudotumour in two parts of the maxilla: case report.

Haemophilic pseudotumour is a rare disease that occurs most often in femur, tibia, ilium or pelvic bone of a patient with haemophilia. Thus far, there have been only 31 reported cases in jaw bones and paranasal sinuses. Among them, the mandible is a more common site than the maxilla or paranasal sinuses. Here, we report a case of haemophilic pseudotumour in two parts of the maxilla. Contrast-enhanced CT showed an expansive and thinly corticated lesion with fluid attenuation at the left anterior maxilla which seemed like a post-operative maxillary cyst, ameloblastoma or odontogenic cyst. In addition, the thickened left palatal process of the maxilla seemed like fibrous dysplasia or intraosseous vascular malformation. Since haemophilic pseudotumour is not pathognomonic in radiological findings, when a patient who suffered from haemophilia or had taken anticoagulating agents has jaw lesion, haemophilic pseudotumour should be included in a differential diagnosis.

Clinical, instrumental, serological and histological findings suggest that hemophilia B may be less severe than hemophilia A.

Recent evidence suggests that patients with severe hemophilia B may have a less severe disease compared to severe hemophilia A. To investigate clinical, radiological, laboratory and histological differences in the arthropathy of severe hemophilia A and hemophilia B, 70 patients with hemophilia A and 35 with hemophilia B with at least one joint bleeding were consecutively enrolled. Joint bleedings (<10, 10-50, >50), regimen of treatment (prophylaxis/on demand), World Federation of Hemophilia, Pettersson and ultrasound scores, serum soluble RANK ligand and osteoprotegerin were assessed in all patients. RANK, RANK ligand and osteoprotegerin expression was evaluated in synovial tissue from 18 hemophilia A and 4 hemophilia B patients. The percentage of patients with either 10-50 or more than 50 hemarthrosis was greater in hemophilia A than in hemophilia B (P<0.001 and P=0.03, respectively), while that with less than 10 hemarthrosis was higher in hemophilia B (P<0.0001). World Federation of Hemophilia (36.6 vs. 20.2; P<0.0001) and ultrasound (10.9 vs. 4.3; P<0.0001) score mean values were significantly higher in hemophilia A patients. Serum osteoprotegerin and soluble RANK ligand were decreased in hemophilia A versus hemophilia B (P<0.0001 and P=0.006, respectively). Osteoprotegerin expression was markedly reduced in synovial tissue from hemophilia A patients. In conclusion, the reduced number of hemarthrosis, the lower World Federation of Hemophilia and ultrasound scores, and higher osteoprotegerin expression in serum and synovial tissue in hemophilia B suggest that hemophilia B is a less severe disease than hemophilia A. Osteoprotegerin reduction seems to play a pivotal role in the progression of arthropathy in hemophilia A.

A comparison between MRI, sonography and Functional Independence Score in Haemophilia methods in diagnosis, evaluation and classification of arthropathy in severe haemophilia A and B.

Evaluation of joints in children with haemophilia is important in detecting abnormalities, staging their severity and following the effects of treatment. The aim of this study is to evaluate the correlation of FISH score (Functional Independence Score in Haemophilia) with the scores obtained by MRI and sonography for the diagnosis, evaluation and classification of arthropathy in severe haemophilia. In this cross-sectional study on 25 severe haemophilia patients, FISH, MRI and sonography procedures were performed in the elbow or knee joint. All patients' information, including age, type of haemophilia, affected joint, scores of MRI, sonography and FISH, dose of factor consumed, weight and prophylaxis protocol were collected and analysed. Among the 25 patients (age range of 11-70 years), 22 patients were haemophilia A and three patients were haemophilia B. Affected joints were right knee in 12 patients, left knee in nine and right elbow in four. There was only a statistically significant negative correlation between FISH and MRI Additive (A) scale (rs = -0.537, P = 0.006). Considering cartilage loss domain (related MRI A scale: 13-20), 20 patients (80%) were classified in this group with FISH scores ranged from 17 to 22. On the basis of our results, FISH scores in severe haemophilia patients were negatively correlated with MRI A scale. Also, it seems that a FISH score less than 22 could be considered as loss of cartilage; however, due to the small number of our patients, it needs further assessment in different populations.

Rapid musculoskeletal ultrasound for painful episodes in adult haemophilia patients.

Little objective information exists about musculoskeletal bleeding patterns in haemophilic arthropathy. Bleeding is assumed to be the cause of painful joints or muscles. Clotting factor treatment is provided empirically, but often does not alleviate pain. We hypothesized that perception of pain aetiology is unreliable, and introduced point-of-care high-resolution musculoskeletal ultrasound (MSKUS) to differentiate intra-articular bleeds vs. joint inflammation, and intra-muscle bleeds vs. other regional pain syndromes. To assess painful musculoskeletal episodes in adult haemophiliacs, we used rapid MSKUS, employing grey scale and power Doppler examination. Forty episodes in 30 adult haemophiliacs were evaluated. Thirty three of the 40 episodes were patient-reported as 'bleeding', five as 'arthritis-type' pain and two as 'undecided'. Of the 33 bleeding reports, only 12 were confirmed by MSKUS; the other episodes revealed other pathology. In contrast, three of five perceived arthritis flares were reclassified as bleeds. Similarly, physician assessment was incorrect in 18 of 40 instances. Swelling and warmth were present in approximately half of confirmed bleeding and non-bleeding episodes, and therefore not useful clinically. Few of the painful episodes were symptom controlled at the time of MSKUS. Management changed based on objective imaging findings in >70% of episodes, which resulted in symptom improvement >60% of the time. Significant discrepancies exist between MSKUS findings and patient/physician-perceived pain classification as bleeding or other musculoskeletal symptoms. Current practice of prescribing clotting factor or conservative measures based on pain perception seems inadequate and suggests that point-of-care imaging should be included into modern haemophilia care.

An MRI scale for assessment of haemophilic arthropathy from the International Prophylaxis Study Group.

Evaluation of prophylactic treatment of haemophilia requires sensitive methods. To design and test a new magnetic resonance imaging (MRI) scale for haemophilic arthropathy, two scales of a combined MRI scoring scheme were merged into a single scale which includes soft tissue and osteochondral subscores. Sixty-one joint MRI's of 46 patients with haemophilia were evaluated by four radiologists using the new and older scales. Forty-six of the joints were evaluated using two X-ray scales. For all MRI scores, interreader agreement and correlations with X-ray scores and lifetime number of haemarthroses were analysed. The interreader agreement intraclass correlation coefficient was 0.82, 0.89 and 0.88 for the soft tissue and osteochondral subscores and the total score, as evaluated according to the new MRI scale, compared to 0.80 and 0.89 as for the older scales. The total score and osteochondral subscore according to the new scale, as well as scores according to the older scales were correlated (P < 0.01) with number of haemarthroses (Spearman correlation 0.35-0.68) and with the X-ray scores (Spearman correlation 0.40-0.76), but no correlation (P > 0.05) was found between the soft tissue subscore of the new MRI scale and the X-ray scores. The new MRI scale is simpler to apply than the older and has similar reader reliability and correlation with lifetime number of haemarthroses, and by separating soft tissue and osteochondral changes it gives additional information. The new scale is useful for analyses of early and moderate stages of arthropathy, and may help to evaluate prophylactic haemophilia treatment.

Peripheral quantitative computed tomography (pQCT) reveals alterations in the three-dimensional bone structure in children with haemophilia.

Children with haemophilia are at risk of suboptimal bone mass accrual and low bone mineral density (BMD). We recently demonstrated that although BMD in Finnish children with haemophilia was within the normal range, their whole body BMD was significantly lower and hypercalciuria more prevalent than in controls. This study sought to determine the bone structure and strength in physically active children with haemophilia. To investigate the underlying mechanisms in this group, we conducted a case-control study to assess bone structure and strength by peripheral quantitative computed tomography (pQCT) at the radius. The study group comprised 29 patients (mean age 12.2 years) and 46 age-matched controls. Children with haemophilia had decreased total BMD Z-score at the distal radius (P ≤ 0.001), but increased cortical bone density at the proximal radius (P ≤ 0.001). Total bone area at the proximal radius was significantly lower in children with haemophilia (P = 0.002), whereas there were no differences in cortical bone area or in polar Strength-Strain Index, a parameter of bone strength, between the patients and controls. Patients with mild to moderate haemophilia and on-demand treatment had inferior bone strength compared to those with moderate to severe haemophilia and prophylaxis. Our findings suggest altered skeletal development in patients with haemophilia in the radius, resulting in smaller bone size and higher cortical bone density. Importantly, bone strength at the radius appears equal to healthy children. Prophylactic treatment seems to have a beneficial effect on bone health.

Medical radiation exposure in children with bleeding disorders: an institutional experience.

Patients with bleeding disorders may be exposed to ionizing radiation during medical care. We hypothesized that children with severe haemophilia may have higher radiation exposure than those with mild bleeding disorders (MBDs). To compare medical radiation exposure rates between children with severe haemophilia and MBDs. Charts of 35 pediatric patients with severe haemophilia were randomly selected from a database of active male patients followed in our bleeding disorders clinic from 2000 to 2010. Case patients were age and sex matched with two control patients with MBDs [Type 1 von Willebrand disease (VWD) or mild platelet function defect (PFD)]. By retrospective review, data on radiation exposure in millisieverts (mSv) was collected from radiological studies performed within Emory/CHOA. The rates of exposure between cohorts were compared using the Mann-Whitney Test. Case patients had a mean of 11.3 (median 8, IQR = 29) radiographic studies compared with 1.8 (median 1, IQR = 11) for controls (P < 0.001). The mean effective dose of radiation per patient per year of study was two mSv for case patients (median 0.4, IQR = 3) and 0.4 mSv for control patients (median 0.01, IQR = 0.3) (P < 0.001). Overall, 1.4% of controls and 31.4% of cases accumulated high to very high levels of exposure ( > 20 mSv). Case patients with severe hemophilia accumulated significantly more medical radiation exposure than controls. While the use of ionizing radiation is often necessary for management of these patients, avoidance of unnecessary exposure along with exploration of alternative imaging techniques and low dose protocols should be considered whenever possible.

Outcome of long-term prophylaxis after cerebral hemorrhage in a patient with severe hemophilia B.

Reports of intracerebral hemorrhage (ICH) in patients with hemophilia B are relatively rare. We describe the first clinical results of the use of a monoclonal antibody purified factor IX (FIX) concentrate (Mononine) after an ICH and the long-term outcome of prophylaxis with this product to prevent recurrences. A 44-year-old male with severe hemophilia B was referred to our department because of nausea, vomiting, left lower limb hemiplegia, and left arm paresis. Computed tomography (CT) revealed a right frontal intraparenchymal bleed. The patient was treated with replacement therapy with FIX for 40 days. Computed tomography scans performed on day 40 after the event showed complete disappearance of the cerebral hematoma from the parenchymal tissue. Subsequently, the patient received 25.6 IU/kg(-1) of FIX twice a week. At the 48-month follow-up visit, no more major or minor bleeding events had occurred. Long-term prophylaxis after ICH is recommended.

Ultrasound detects joint damage and bleeding in haemophilic arthropathy: a proposal of a score.

Haemarthrosis triggers haemophilic arthropathy (HA) because bleeding starts synovitis immediately, damages cartilage and leads to loss of function and disability. The aim of our study was to investigate the capacity of ultrasonography (US) in detecting bleeding and joint damage in HA. The joints of 62 patients (pts) with haemophilia A or haemophilia B were consecutively evaluated and scored (score ranging from 0 to 21) for effusion (E), bone remodelling (BR), cartilage damage (CD), synovial hypertrophy (SH), haemosiderin (H), osteophytes (O), haemarthrosis (Hae), erosion (Er) and fibrotic septa (FS) with US. X-rays [Pettersson Score (PXS)] were performed in 61 patients and clinical evaluation [World Federation Haemophiliac orthopaedic score (WFHO)] was performed in all patients. A total of 20 healthy subjects and 20 patients affected by Rheumatoid Arthritis (RA) were used as controls. Power Doppler US (PDUS) was performed in all patients on the knee, ankle and elbow joints. A total of 83 joints were studied (50 knees; 12 elbows and 21 ankles). US showed effusion in 57 joint, bone remodelling in 62, cartilage damage in 64, synovial hypertrophy in 45, haemosiderin in 39, osteophytes in 30, haemarthrosis in 24, erosion in 5 and fibrotic septa in 3. The X-rays score showed remodelling in 47 joints, narrowing joint space in 44, displacement/angulation in 39, osteoporosis in 42, subchondral irregularity in 44, subchondral cyst formation in 37, osteophytes in 36 and erosions in 25. The US score in healthy subjects was always ≤ 5 (range 0 to 4). In haemophiliacs, 34 of 83 joints showed US score ≤ 5, and 49 US score > 5. Joints with US score ≤ 5 had a low PXS (SRCC = 0.375, P < 0.01) and joints with US score > 5 showed a high PXS (SRCC = 0.440, P < 0.01). A significant correlation between US score and PXS for bone remodelling [Spearman's rho Correlation Coefficient (SRCC) = 0.429, P < 0.01] and for osteophytes (SRCC = 0.308, P < 0.05) was found. The correlation between the US score and number of bleedings in 83 joints was very significant (SRCC = 0.375, P < 0.01). A total of 24 bleeding joints were identified and verified with aspiration of haematic fluid. US may detect bone and cartilage alterations and synovitis. Indeed, PDUS identified bleeding also in asymptomatic joints and was able to show different entity of haemarthrosis. US may be a feasible and reliable tool to evaluate joint modifications in HA.

[Hemorrhagic parapneumonic effusion in a 64 year-old patient as the first symptom of hemophilia B]. / Krwisty wysiek parapneumoniczny jako pierwszy objaw hemofilii B u 64-letniego mezczyzny.

Hemophilia B is an inherited, X chromosome-linked disease. It is usually diagnosed in childhood, sometimes in adolescence. The commonest symptoms include spontaneous or post-traumatic bleeding into the joints and/or muscles, as well as mucosal bleeding. Respiratory symptoms are rarely reported. We present the case of a 64 year-old man in whom bloody parapneumonic effusion (hemothorax) was the first symptom of hemophilia B. The reason for prolonged activated partial thromboplastin time (APTT) found on admission has not been elucidated. Since antibiotic therapy and pleural tube thoracostomy with intrapleural streptokinase were found to be ineffective, video-assisted thoracic surgery was performed with the right lung decortication. Post-operative treatment was complicated by massive pleural bleeding requiring two subsequent thoracotomies. Additional blood tests revealed factor IX deficiency and resulted in hemophilia B being diagnosed. The presented case proves that hereditary bleeding disorders may be diagnosed even in late adulthood. Intrapleural bleeding related to pneumonia and pleural inflammation might be the first presenting symptom. Hemophilia should be considered as a potential cause of APTT prolongation, even in an elderly patient with atypical presentation. Explaining the reason for APTT prolongation before the surgical procedure could have allowed to avoid severe bleeding in the described patient.

An attempt to improve the clinical scale for assessment of haemophilic arthropathy in children.

Of the methods used to evaluate haemophilic arthropathy, clinical joint score can only detect advanced and not minor changes, which usually occur in younger patients. In addition, the currently used clinical scores are poorly correlated with the MRI and X-rays scales. In an attempt to address these shortcomings, a modification of Stockholm clinical scale was designed in which elements of clinical information were included. This new scale was applied in 165 joints of 40 patients with haemophilia A and B and the results were statistically analyzed for its capacity to detect early joints alterations. Furthermore, the adjusted score was compared with Pettersson's radiological score and Denver's MRI score, which can detect early signs of arthropathy. The adjusted scale (a) revealed the earliest abnormalities of haemophilic arthropathy and its correlation with the Pettersson and Denver scores is better than those of Stockholm's scale, (b) provided prediction of the Denver score and (c) was simple and safe to be performed and it could easily be repeated.

Prevalence and risk factors associated with decreased bone mineral density in patients with haemophilia.

Osteoporosis in adult males is an under-recognized problem. Patients with haemophilia have several predisposing factors for developing decreased bone mineral density (BMD) including prolonged periods of immobility, reduced weight bearing and co-morbidities associated with bone loss. To establish prevalence and risk factors associated with decreased BMD in patients with haemophilia. Adults with moderate or severe haemophilia A or B underwent dual-energy X-ray absorptiometry (DXA). BMD was correlated to laboratory values, joint mobility measurements and physical activity questionnaires. Thirty patients completed evaluations. The median age was 41.5 years (range 18-61). Median lowest T-score by DXA was -1.7 (range: -5.8 to +0.6), with the femoral neck being the site of the lowest T-scores. Based on World Health Organization criteria, 70% of patients had decreased BMD. Twenty-seven per cent of the participants (n = 8) had osteoporosis and 43% (n = 13) had osteopenia. Variables associated with increased bone loss included lower serum 25-hydroxyvitamin D levels (P = 0.03), lower body mass index (P = 0.047), lower activity scores (P = 0.02), decreased joint range of motion (P = 0.046), HIV (P = 0.03), HCV (P = 0.02), history of inhibitor (P = 0.01) and age (P = 0.03). Adults with haemophilia are at increased risk for developing osteoporosis. A history of HCV and HIV infections, decreased joint range-of-motion, decreased activity levels, history of an inhibitor and low body weight predict bone loss and suggest a population to target for screening. A high prevalence of vitamin D insufficiency was observed. Future studies should investigate interventions, including vitamin D supplementation, to prevent bone loss and fractures for this at-risk population.

Endothelial dysfunction in haemophilia patients.

Haemophilia patients may develop cardiovascular diseases, suggesting that their clotting defect does not protect them completely from atherosclerosis and its complications. We aimed to evaluate cardiovascular risk factors and, for the first time, the presence of endothelial dysfunction in middle-aged haemophilia patients. We studied 40 patients with haemophilia A and B (24 with moderate-severe disease and 16 with mild disease), and 40 healthy controls. Flow-mediated dilation (FMD), carotid ultrasound (US) intima media thickness (IMT), arterial blood pressure, body mass index (BMI), cholesterol, triglycerides, glucose, insulin, lipoprotein(a) and homocysteine levels were measured, and PAI-1 and t-PA levels before and after venous occlusion (VO), and antibodies to HIV, HBV and HCV were assayed. At least one cardiovascular risk factor was detected in 87.5% of patients, and 2 or more in 47.5% of cases. At US exam, none of the patients had significant carotid stenosis or significant differences in IMT compared to controls. In contrast, all the patients had a significant FMD impairment, associated with a reduced t-PA release after VO in 70% of cases. PAI-1 levels significantly correlated with BMI, triglycerides and insulin values. Fifteen haemophilia patients with chronic viral hepatitis and/or HIV infection showed a significantly lower FMD than patients without active infection. We found an endothelial dysfunction with impaired FMD and t-PA release in our haemophilia patients, usually associated with cardiovascular risk factors. Other pathogenic mechanisms, such as chronic viral infections, are likely to be involved in this endothelial damage, however.

Reliability and construct validity of the compatible MRI scoring system for evaluation of elbows in haemophilic children.

We assessed the reliability and construct validity of the Compatible MRI scale for evaluation of elbows, and compared the diagnostic performance of MRI and radiographs for assessment of these joints. Twenty-nine MR examinations of elbows from 27 boys with haemophilia A and B [age range, 5-17 years (mean, 11.5)] were independently read by four blinded radiologists on two occasions. Three centres participated in the study: (Toronto, n = 24 examinations; Atlanta, n = 3; Cuiaba, n = 2). The number of previous joint bleeds and severity of haemophilia were reference standard measures. The inter-reader reliability of MRI scores was substantial (ICC = 0.73) for the additive (A)-scale and excellent (ICC = 0.83) for the progressive (P)-scale. The intrareader reliability was excellent for both P-scores (ICC = 0.91) and A-scores (ICC = 0.93). The total P- and A-scores correlated poorly (r = 0.36) or moderately (r = 0.54), but positively, with clinical-laboratory measurements. The total MRI scores demonstrated high accuracy for discrimination of presence or absence of arthropathy [P-scale, area-under-the-curve (AUC) = 0.94 +/- 0.05; A-scale, AUC = 0.89 +/- 0.06], as did the soft tissue scores of both scales (P-scale, AUC = 0.90 +/- 0.06; A-scale, AUC = 0.86 +/- 0.06). Areas-under-the-curve used to discriminate severe disease demonstrated high accuracy for both P-MRI scores (AUC = 0.83 +/- 0.09) and A-MRI scores (AUC = 0.87 +/- 0.09), but non-diagnostic ability to discriminate mild disease. Similar results were noted for radiographic scales. In conclusion, both MRI scales demonstrated substantial to excellent reliability and accuracy for discrimination of presence/absence of arthropathy, and severe/non-severe disease, but poor to moderate convergent validity for total scores and non-diagnostic discriminant validity for mild/non-mild disease. Compared with radiographic scores, MRI scales did not perform better for discrimination of severity of arthropathy.

Osteoporosis in young haemophiliacs from western India.

Arthropathies and joint deformities in patients with severe hemophilia result in prolonged immobilization, reduced physical activity, and predispose them for osteoporosis. This can lead to an increasing tendency of bone fragility and fractures in patients after trivial trauma. The aim of this study was to find out (i) the prevalence of osteoporosis in hemophilia patients and (ii) the association of osteoporosis with hemophilic arthropathy and related restricted physical activity. In this case-control study, 50 consecutive severe hemophilia patients aged between 20 and 50 years were evaluated for osteoporosis with measurement of bone mass density (BMD) by a DEXA scan and values were compared with that of 50 sex matched normal healthy controls. Major joints of the limbs were evaluated to determine the extent of joint damage and related disability. Forty-two patients had severe hemophilia A and 8 patients severe hemophilia B (efficient factor activity < 0.01 U/ml). BMD values (gms/cm(2)) of lumbar spine and left hip of the patients were significantly lower than that of controls (0.825 vs. 0.939; P < 0.0001 and 0.725 vs. 0.938; P < 0.0001, respectively). The incidence of osteoporosis (T score: -2.5 or more) was significantly higher in hemophiliacs. Incidence of fractures in adult life was also significantly higher in hemophiliacs compared to controls (12% vs. 0%). There was statistically significant correlation between joint evaluation scores and BMD of hip, but not with that of the lumbar spine. There was no correlation between Hepatitis-C virus status and BMD of any site. This shows that development of osteoporosis is a significant problem in patients with severe hemophilia in this country. Hence appropriate preventive measures such as early treatment and adequate mobilization, exercises, encouragement to participate in sporting activities, early assessment of bone density, and administration of anti-osteoporotic therapy is recommended.