Search

Background: Patients with severe haemophilia suffer from bleeding-related joint changes in which the ankle joint is most frequently affected. In the resulting gait changes, the forefoot is involved by reducing the foot pressure. However, it is unclear which changes in foot pressure are present in the individual's foot zones.Research Question: The aim of the study was to determine whether compensation mechanisms are present in the foot zones regarding the peak pressure under dynamic conditions and to identify possible underlying mechanisms for gait changes.Methods: In a controlled cross-sectional study, a pedobarography was performed during gait with a standardized speed (3 km/h) in patients with haemophilia (PwH;n = 40) and healthy controls (Con;n = 40). Pressure pain thresholds (PPT) were detected, and Haemophilia Joint Health Score (HJHS) was performed to determine the current joint status.Results: PwH showed a decreased peak pressure in metatarsals II-IV and heel compared to Con. Patients with major-affected ankle joints (determined with the HJHS) showed a decreased single-step length, stride-length and stride-time. Accordingly, the cadence was increased by 10 ± 11 steps/min in PwH compared to Con. Furthermore, PwH showed decreased ankle range of motion (ROM) in HJHS and an altered pain perception due to reduced PPT.Significance: PwH showed a changed gait pattern in peak pressure compared to Con. A restricted rolling behavior, which might be caused by movement restrictions and pain sensation, leads to reduced pressure in the center forefoot, resulting in a shorter stride-length. Future therapies should focus on maintaining joint mobility for better rolling behavior and improving ankle joints' stability to achieve a balanced load between the midfoot, heel, and forefoot. The use of insoles adapted to our data, based on group differences between PwH and Con, could be supportive in this case. [ABSTRACT FROM AUTHOR]

Patients with hemophilia are at high risk of bleeding following oral surgery. As an X-linked recessive chromosomal bleeding disorder it is very rare in female patients. This is the first described case of management of third molar removal in a female patient suffering from severe hemophilia B. Excellent hemostasis was achieved by following a protocol using defined pre- and postoperative doses of factor IX and local hemostatic measures of collagen fleece, fibrin glue, primary suture, and tranexamic acid solution. Following defined protocols is essential in the management of oral surgery in patients with hemophilia and helps to prevent postoperative hemorrhages. [ABSTRACT FROM AUTHOR]

To conduct a systematic review of the literature reporting efficacy and safety of recombinant factor VIIa (rFVIIa) for the treatment of bleeding in acquired haemophilia and, if data permitted, undertake a meta-analysis of the current evidence. MEDLINE®, Embase®, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for all studies on rFVIIa treatment in acquired haemophilia. Heterogeneity of included studies was measured using the inconsistency index (I2). Of the 2353 publications screened, 290 potentially relevant references were identified: 12 studies published in 32 publications met inclusion criteria. In total, 1244 patients and 1714 bleeds were included (671 patients received rFVIIa treatment for 1063 bleeds). In seven of 12 studies, the initial dose of Recombinant FVIIa was 90 ± 10 μg/kg. Recombinant FVIIa was used as first-line therapy in the majority of cases. Median number of doses administered ranged from 10 to 28. Between 68 and 74% of bleeds were spontaneous, whereas 4-50% were traumatic. Thirty-nine to 90% of bleeds were severe. Haemostatic effectiveness was > 90% in 5/6 studies for both patient and bleed level. Recombinant FVIIa had a favourable safety profile with low risk of general adverse events and thromboembolic-associated events. The heterogeneity of the studies and data precluded a meta-analysis. Recombinant FVIIa demonstrated effectiveness for the treatment of bleeds and had a good safety profile. It is apparent from these data that there is a need for more standardised measures of clinical effectiveness in acquired haemophilia to enable comparison and pooling of results in the future. [ABSTRACT FROM AUTHOR]

Background/Aims: To investigate the dynamic plantar loading characteristics, postural stability and the effectiveness of an exercise programme in children with recurrent ankle haemarthrosis. Methods: In an exploratory study, 56 children with haemophilia (Group A) and 23 typically developing children (Group B) were initially assessed. Group A received a progressive exercise programme twice a week for 6 weeks in succession. Midstance plantar loading and the dynamic limit of stability were measured using Tekscan HR MatTM pressure measurement system and Biodex Balance System respectively. Findings: Heel pressure in Group A was significantly lower than Group B (P<0.05), whereas mid-foot, forefoot, and hallux pressure were significantly higher (P<0.05). Also, Group A showed poorer postural stability (P<0.05). Furthermore, a significant correlation between postural stability and plantar loading measures was indicated in Group A. Following the completion of 6 weeks of exercises, the plantar pressure (except the medial mid-foot) and postural stability (except the mediolateral stability) for Group A were not significantly different in comparison to Group B (P>0.05). Conclusion: Dynamic plantar loading provides a potentially valuable directory for the clinicians to understand variations of postural stability in children with ankle haemarthrosis. Further, adherence to a 6-week exercise rehabilitation programme might be helpful. [ABSTRACT FROM AUTHOR]

Joint bleeding and resultant arthropathy are major determinants of quality of life in haemophilia patients. We previously developed a mesenchymal stromal cell (MSC)-based treatment approach for haemophilic arthropathy in a mouse model of haemophilia A. Here, we evaluated the long-term safety of intra-articular injection of lentivirally transduced autologous MSCs in non-human primates. Autologous bone-marrow-derived MSCs transduced with a lentiviral vector expressing coagulation factor VIII (FVIII) were injected into the left knee joint of cynomolgus monkeys. We first conducted codon optimization to increase FVIII production in the cells. Lentiviral transduction of autologous MSCs resulted in a significant increase of FVIII in the culture supernatant before transplantation. We did not find any tumour generation around the knee structure at 11-16 months after injection by magnetic resonance imaging. The proviral sequence of the simian immunodeficiency virus lentiviral vector was not detected in the heart, lungs, spleen, liver, testis, or bone marrow by real-time quantitative PCR. We confirmed the long-term safety of intra-articular injection of transduced MSCs in a non-human primate. The procedure may be an attractive therapeutic approach for joint diseases in haemophilia patients. [ABSTRACT FROM AUTHOR]

Hemophilia is a severe congenital bleeding disorder associated with both spontaneous and traumatic bleeding episodes that can require emergent medical evaluation. Many persons with hemophilia (PWH) utilize the emergency department for the initial management of acute bleeding events. Prompt administration of factor replacement products is crucial in controlling acute bleeds and minimizing potential associated morbidity. PWH who have inhibitory antibodies can be especially difficult to treat, as they often require by-passing agent therapies to obtain hemostatic control. Although consultation with an experienced hematologist is always warranted, initial management of acute complications in hemophilia is emergent, which necessitates emergency care providers to have a strong understanding of the current treatment principles in this complex condition. [ABSTRACT FROM AUTHOR]

Antibody formation against therapeutic agents, such as tumor necrosis factor inhibitors and Factor VIII, that leads to treatment failure has become a major challenge in the treatment of rheumatoid arthritis and hemophilia. It is well known that anti-CD154 antibodies have the highest potential to inhibit these types of adverse immune responses. Nevertheless, the formation of thromboemboli is the major hurdle in the clinical application of these anti-CD154 blocking antibodies. For this, we attempted to derive an idea as to how this major complication can be eliminated. Consequently, we developed a novel anti-CD154 chimeric antibody, which was made by genetic modification of a portion of human IgG4 Fc. This antibody has an almost comparable antigen binding affinity to a previously developed 5C8 clone and near completely inhibited CD40-CD154 interaction and T cell-dependent B cell activation in vitro . Even under the condition, where we injected immune complexes comprised of RD-05 and CD154 antigen, the formation of thromboembolism was not seen in human FcγRIIA-transgenic mice, whereas the converse was exactly true in the case of 5C8 antibody. Notably, just two injections of RD-05 antibody was sufficient to inhibit the antibody formation against adalimumab during 3–4 months in cynomolgus macaques, in which adalimumab was repeatedly injected for 12 weeks. Based on these findings, we suggest that this RD-05 antibody can be applied to antibody-mediated autoimmune diseases, including systemic lupus erythematosus and immune thrombocytopenic purpura. [ABSTRACT FROM AUTHOR]

Purpose: Total knee arthroplasty (TKA) for patients with end-stage haemophilic arthropathy is considered to be a successful procedure with satisfying mid- to long-term results. It was the purpose of this study to provide clinical and radiological long-term results of TKAs implanted in a consecutive cohort of haemophilic patients.Methods: Primary TKA was performed in 43 consecutive knees in 30 haemophilic patients. After a mean of 18 (SD ± 4) years, 15 patients (21 knees) with a mean age of 58 (SD ± 8) years were available for follow-up. The outcome was assessed using the Knee Society score, WOMAC, SF-36, Kaplan-Meier survivorship analysis as well as radiographic evaluation of radiolucency.Results: In 13 (30%) of the 43 consecutive knees, revision surgery was necessary due to infection or aseptic loosening, among which eight (19%) due to aseptic loosening and five (12%) due to haematogenous infection. The calculated 20-year survival rates with revision for any reason or infection as the end points were 59 and 82%, respectively. All patients with the primary TKA in situ observed progressive radiolucent lines around the implants at the final follow-up. The Knee Society clinical and functional score significantly improved from pre- (36 points; SD ± 16 and 62 points; SD ± 19) to post-operatively (73 points; SD ± 15 and 78 points; SD ± 18; p < 0.001). Eighty-six per cent rated their result as either good or excellent. Whereas flexion did not improve, flexion contracture could be reduced significantly from 18° (SD ± 12) to 6° (SD ± 5; p < 0.001) post-operatively.Conclusion: Total knee arthroplasty in haemophilic patients is associated with high revision, loosening and infection rates after 18 years. However, if revision can be avoided, joint replacement in haemophilic patients helps to relieve pain, achieve higher subjective satisfaction and to restore knee function. Level of evidence IV. [ABSTRACT FROM AUTHOR]

This is an article reviewing the management of pregnant women with factor XI (FXI) deficiency. Retrospective review of the electronic records of 67 pregnancies in 25 women with FXI deficiency over a ten-year period was undertaken. All women received care at St Mary's Tertiary Referral Obstetric/Haematology Clinic for some or all of their pregnancies. Outcome measures included antenatal complications, mode of delivery, anaesthesia provided and postpartum haemorrhage (PPH) and management required. A positive bleeding history was identified in 50% of women prior to pregnancy. Fifteen pregnancies (22%) ended in first trimester miscarriage; there was 1 termination of pregnancy. Two pregnancies were complicated by Antepartum haemorrhage. Of the remaining 51 pregnancies there were 50 live births - 2 preterm and 48 at term. There was one antenatal (34 weeks gestation) stillbirth of a growth restricted baby and one neonatal death secondary to severe prematurity (24 weeks gestation). Twenty -five babies delivered vaginally (20 spontaneous and 5 instrumental). The remaining 26 were delivered by Caesarean section (9 elective and 17 emergency). A sub-analysis of 22 operative deliveries was reviewed; this suggested that regional anaesthesia was safe in selected women with FXI deficiency - a selection that was based on FXI level/range, presence/absence of bleeding history and intended operative intervention.Solvent detergent treated Fresh Frozen Plasma (SD-FFP/Octaplas) and Tranexamic Acid (TXA) were given to those considered vulnerable -an individualised decision made by the multidisciplinary team in accordance with BCSH guidance. Primary PPH complicated 10/51 (15%) deliveries. The commonest cause of PPH was due to atony. Secondary PPH was only seen in only one case. Bleeding in women with FXI deficiency is highly variable and, whilst it does not directly correlate with Factor XI levels, provision of replacement therapy is required if FXI levels are <15 IU/dL as per BCSH guidance. Women with Factor XI levels >40 IU/dL are considered safe for regional anaesthesia following prophylactic FFP as suggested by sub group analysis. Treatment of women with rare bleeding disorders during pregnancy should be by a multidisciplinary team of specialists, to include Haematologist, Anaesthetist and Obstetrician, all of whom have an interest in bleeding disorders in pregnancy. Decisions should then be individualised, based on the presence/absence of a bleeding history and the third trimester FXI levels. Delivery does not have to be by Elective Caesarean. With appropriate care both operative vaginal delivery and regional anaesthesia can be facilitated. [ABSTRACT FROM AUTHOR]

The article focuses on findings of a study on successful management of refractory hematuria with recombinant porcine factor VIII replacement for pediatric congenital hemophilia A with high-titre inhibitor. Topics include the most significant therapeutic complication of hemophilia A, which is development of neutralizing antibodies against factor VIII; treatment of patients with high-titre inhibitors (CHAWI); and ocurrence of Haematuriaamong persons with hemophilia.

Objective: Bleeding complications either spontaneously or post-operatively are very common in patients with haemophilia. Sometimes these bleeding complications remain unresponsive despite being on high dose of clotting factor replacement. The aim was to assess the role of endovascular embolization in patients with haemophilia in (a) treating haemorrhagic complications due to local causes refractory to clotting factors substitution and (b) reducing intraoperative blood loss in elective pseudotumour surgery. Methods: 10 patients seen between January 2000 and April 2015 with severe haemophilia A or B who had unexplained profuse persistent bleeding or required large pseudotumour excision and were taken up for digital subtraction angiography and embolization were included in the study. Data of all these patients were reviewed using the computerized hospital information system and picture archiving and communication system. Details including indications for the procedure, patient preparation for the procedure, imaging findings, details of angiography with intervention, if any, and outcome as well as follow-up data were analyzed. Results: In 6 of these 10 cases, bleeding was spontaneous, in 2 cases due to trivial fall and in 2 cases due to post-operative bleeding. Angiography in these patients revealed vascular blush, abnormal hypervascularity or active extravasation. In all 10 patients, an embolization procedure was performed, with bleeding controlled in 8 patients. There were no procedure-related complications during the procedure, post-procedure bleeding or haematoma at the site of arterial access. One patient had recurrence of bleeding for whom surgical exploration was required, and one patient had significant bleeding intraoperatively which was controlled with high-dose clotting factors, blood transfusion and fresh frozen plasma intraoperatively. Conclusion: Endovascular embolization is a safe, effective and cost-saving procedure in arresting bleeding in selected patients with severe haemophilia who are unresponsive to adequate clotting factor replacement and where local vascular causes could be contributing to the bleeding. Pre-operative embolization is also a good procedure to reduce intraoperative blood loss in patients with large pseudotumours. [ABSTRACT FROM AUTHOR]

Primary prophylaxis is a method of haemostatic management to prevent bleeding and arthropathy in patients with severe haemophilia. The aim of this study was to evaluate the usefulness of primary prophylaxis in patients with severe haemophilia A. This study included 15 patients with haemophilia A who received primary prophylaxis at our institution for a minimum of 5 years. We evaluated the annualized bleeding ratio of joints or other sites, current joint function, and X-ray images and MRI scans taken when patients were 6 years old. The range of patients' ages at the end of the study was 6.2-16.8 years, and at the start of primary prophylaxis it was 0.8-2.4 years. Factor VIII concentrates (25-40 units kg(-1) dose(-1)) were administered 3 times/week or every other day, according to the Swedish protocol. Mean joint and non-joint annualized bleeding ratios were 0.49 ± 0.5 and 1.54 ± 1.69, respectively. At the final evaluation, all patients displayed a normal range of motion for both elbows, knees, and ankles. The radiography and MRI findings at the age of 6 were unremarkable in all patients. Overall, primary prophylaxis for patients with severe haemophilia A was performed safely, reduced the number of bleeding events, and prevented progression to arthropathy. [ABSTRACT FROM AUTHOR]

The introduction of clotting factor concentrates has transformed the lives of persons with inherited bleeding disorders. With the use of prophylactic treatment, it is now possible to prevent bleeding in these individuals. The early concentrates were contaminated with the HIV and hepatitis C viruses (HCV) and resulted in major morbidity and mortality in the recipients. Current products are much safer, especially in terms of infectious agents, but other adverse events such as alloantibodies (inhibitors), allergic reactions and thrombotic risks remain of concern. Approximately 30% of previously untreated patients with severe haemophilia A develop inhibitors, making this the most important issue in haemophilia care today. Recently, it was suggested that one of the most commonly used concentrates was associated with a higher inhibitor risk, but this was not supported by the evidence from all studies. Good safety surveillance systems are essential for all diseases and products but are particularly so in the group of individuals with inherited bleeding disorders treated with clotting factor concentrates who have suffered disproportionately from the adverse effects of their treatment. National and multinational systems are now in place to allow reporting of adverse events in patients with inherited bleeding disorders. All clinicians treating individuals with inherited bleeding disorders should prospectively report adverse events to treatment even if they are believed to be common and well recognized. [ABSTRACT FROM AUTHOR]

Haemophilia is a congenital disorder with bleeding episodes as its primary symptom. These episodes can result in negative outcomes including joint damage, loss of active days due to hospitalization and reduced quality of life. Effective treatment, however, can improve the outcome. Registries have been used as a valuable source of information regarding the monitoring of treatment and outcome. The two main aims of this exploratory study were to establish which haemophilia registries publish peer-reviewed outcome assessment research and then to extract, classify and report the treatment outcomes and their extent of use in the retrieved registries. Using relevant keywords, we searched PubMed and Web of Science databases for publications during the period 1990-2015. Retrieved references were screened in a stepwise process. Eligible papers were original full articles on haemophilia outcomes that used data from a computerized patient database. Descriptive results were summarized. Of 2352 references reviewed, 25 full texts were eligible for inclusion in the study. These papers were published by 11 registries ranging from local to international in coverage. It is still relatively rare for registries to produce peer-reviewed publications about outcomes, and most that currently do produce such papers are located in Europe and North America. More information is available on traditional outcomes such as comorbidities and arthropathy than on health-related quality of life or the social and developmental impact of haemophilia on patients. Inhibitors, HIV and viral hepatitis are amongst the most commonly reported comorbidities. Research has focused more on factor consumption and less on hospitalization or time lost at school or work due to haemophilia. Haemophilia registries, especially those at the national level, are valuable resources for the delivery of effective health care to patients. Validated outcome measurement instruments are essential for the production of reliable and accurate evidence. Finally, such evidence should be communicated to physicians, patients, the public and health policymakers. [ABSTRACT FROM AUTHOR]

Background: The development of neutralizing anti-factor VIII alloantibodies (inhibitors) in patients with severe hemophilia A may depend on the concentrate used for replacement therapy.Methods: We conducted a randomized trial to assess the incidence of factor VIII inhibitors among patients treated with plasma-derived factor VIII containing von Willebrand factor or recombinant factor VIII. Patients who met the eligibility criteria (male sex, age <6 years, severe hemophilia A, and no previous treatment with any factor VIII concentrate or only minimal treatment with blood components) were included from 42 sites.Results: Of 303 patients screened, 264 underwent randomization and 251 were analyzed. Inhibitors developed in 76 patients, 50 of whom had high-titer inhibitors (≥5 Bethesda units). Inhibitors developed in 29 of the 125 patients treated with plasma-derived factor VIII (20 patients had high-titer inhibitors) and in 47 of the 126 patients treated with recombinant factor VIII (30 patients had high-titer inhibitors). The cumulative incidence of all inhibitors was 26.8% (95% confidence interval [CI], 18.4 to 35.2) with plasma-derived factor VIII and 44.5% (95% CI, 34.7 to 54.3) with recombinant factor VIII; the cumulative incidence of high-titer inhibitors was 18.6% (95% CI, 11.2 to 26.0) and 28.4% (95% CI, 19.6 to 37.2), respectively. In Cox regression models for the primary end point of all inhibitors, recombinant factor VIII was associated with an 87% higher incidence than plasma-derived factor VIII (hazard ratio, 1.87; 95% CI, 1.17 to 2.96). This association did not change in multivariable analysis. For high-titer inhibitors, the hazard ratio was 1.69 (95% CI, 0.96 to 2.98). When the analysis was restricted to recombinant factor VIII products other than second-generation full-length recombinant factor VIII, effect estimates remained similar for all inhibitors (hazard ratio, 1.98; 95% CI, 0.99 to 3.97) and high-titer inhibitors (hazard ratio, 2.59; 95% CI, 1.11 to 6.00).Conclusions: Patients treated with plasma-derived factor VIII containing von Willebrand factor had a lower incidence of inhibitors than those treated with recombinant factor VIII. (Funded by the Angelo Bianchi Bonomi Foundation and others; ClinicalTrials.gov number, NCT01064284; EudraCT number, 2009-011186-88.). [ABSTRACT FROM AUTHOR]

Background: In patients with severe hemophilia A, standard treatment is regular prophylactic and episodic intravenous infusions of factor VIII. However, these treatments are burdensome, especially for children, and may lead to the formation of anti-factor VIII alloantibodies (factor VIII inhibitors). Emicizumab (ACE910), a humanized bispecific antibody mimicking the cofactor function of factor VIII, was developed to abate these problems.Methods: We enrolled 18 Japanese patients with severe hemophilia A (with or without factor VIII inhibitors) in an open-label, nonrandomized, interindividual dose-escalation study of emicizumab. The patients received subcutaneous emicizumab weekly for 12 weeks at a dose of 0.3, 1.0, or 3.0 mg per kilogram of body weight (cohorts 1, 2, and 3, respectively). The end points were safety and pharmacokinetic and pharmacodynamic profiles. An additional, exploratory end point was the annualized bleeding rate, calculated as 365.25 times the number of bleeding episodes, divided by the number of days in the treatment period as compared with the 6 months before enrollment.Results: Emicizumab was associated with neither serious adverse events nor clinically relevant coagulation abnormalities. Plasma concentrations of emicizumab increased in a dose-dependent manner. Activated partial-thromboplastin times remained short throughout the study. The median annualized bleeding rates in cohorts 1, 2, and 3 decreased from 32.5 to 4.4, 18.3 to 0.0, and 15.2 to 0.0, respectively. There was no bleeding in 8 of 11 patients with factor VIII inhibitors (73%) and in 5 of 7 patients without factor VIII inhibitors (71%). Episodic use of clotting factors to control bleeding was reduced. Antibodies to emicizumab did not develop.Conclusions: Once-weekly subcutaneous administration of emicizumab markedly decreased the bleeding rate in patients who had hemophilia A with or without factor VIII inhibitors. (Funded by Chugai Pharmaceutical; JapicCTI number, 121934.). [ABSTRACT FROM AUTHOR]

Background: Myelofibrosis and acquired hemophilia A is a rare association. To the best of our knowledge only one case of myelofibrosis and acquired hemophilia A has been previously described.Case Presentation: A 66-year-old Caucasian man diagnosed with myelofibrosis evolving in acute myeloid leukemia was referred to us for postoperative bleeding. Hemostatic studies showed prolonged activated partial thromboplastin time, decreased factor VIII coagulation, and a high factor VIII inhibitor titer; these findings led to a diagnosis of acquired hemophilia A for which he was treated with methylprednisolone and recombinant activated factor VII on admission. Due to a lack of response he was subsequently treated with rituximab combined with activated prothrombin complex concentrates. Furthermore, he received azacytidine to treat the underlying hematological malignancies. Immunosuppressive rituximab therapy resolved acquired hemophilia A with marked efficacy.Conclusions: Rapid and accurate diagnosis, effective hemostatic therapy, and timely treatment for underlying disease are important in the management of acquired hemophilia A secondary to hematological malignancy. [ABSTRACT FROM AUTHOR]

Next-generation sequencing has critical applications in virus discovery, diagnostics, and environmental surveillance. We used metagenomic sequence libraries for retrospective screening of plasma samples for the recently discovered human hepegivirus 1 (HHpgV-1). From a cohort of 150 hepatitis C virus (HCV)-positive case-patients, we identified 2 persons with HHpgV-1 viremia and a high frequency of human pegivirus (HPgV) viremia (14%). Detection of HHpgV-1 and HPgV was concordant with parallel PCR-based screening using conserved primers matching groups 1 (HPgV) and 2 (HHPgV-1) nonstructural 3 region sequences. PCR identified 1 HHPgV-1-positive person with viremia from a group of 195 persons with hemophilia who had been exposed to nonvirally inactivated factor VII/IX; 18 (9%) were HPgV-positive. Relative to HCV and HPgV, active infections with HHpgV-1 were infrequently detected in blood, even in groups that had substantial parenteral exposure. Our findings are consistent with lower transmissibility or higher rates of virus clearance for HHpgV-1 than for other bloodborne human flaviviruses. [ABSTRACT FROM AUTHOR]

The article offers information on a study which discusses gastrointestinal (GI) bleeding in children with hemophilia A. It mentions information on importance of early referral to a pediatric gastroenterology unit, timely oesophago- gastro-duodenoscopy (OGD), and collaborative multidisciplinary management. It states that GI bleeding is most commonly caused by genuine GI pathology, especially duodenal ulcers, bleeding from unknown site, and gastritis.

Haemophilia is hereditary bleeding disorder due to absence or deficiency of clotting factors in the blood. Haemophilia is characterized by intra-articular bleeding, often requiring immobilization, which may result in muscle atrophy and impaired proprioception. Patients with haemophilia are at risk of haemarthrosis, soft-tissue haematomas, bruising, retroperitoneal bleeding, intra-cerebral haemorrhage, and post-surgical bleeding. Knee, ankle and elbow joints are more commonly affected by haemophilic bleeding. People with haemophilia who have had many bleeds tend to develop a distinctive posture that may include: flexion deformities of the elbows, knees, and hips; an exaggerated arch in the back plantar-flexed ankles; pelvic asymmetry due to leg length differences; and varying amounts of muscle wasting. Physiotherapy is integral in the management of people with haemophilia. A key goal is to help maintain mobility, muscle strength, and balance. An individualized physiotherapy can raise the quality of life of a patient with haemophilia through increase of the physical function, pain reduction and prevention of bleeding. The 80% of haemophilia patients have no access to pharmacological therapy and part of remaining 20% only receive treatment after a bleeding episode. In both cases, patients develop physical consequences before reaching adulthood require physiotherapy treatment to improve quality of life. [ABSTRACT FROM AUTHOR]

Hemophilic pseudotumor (PT) is a very rare complication of hemophilia consisting of a chronic, encapsulated, hemorrhagic fluid collection occurring both in the soft tissues and/or bone. Radiological features of osseous hemophilic PT are nonspecific and mimic several other benign or malignant bone tumors or infectious processes. Although the diagnosis is usually made on the location of the lesion and by the knowledge of the underlying disease, the radiologist should be aware of the imaging characteristics, in order to avoid misinterpretation as a malignant tumor, as biopsy of these lesions is contraindicated. [ABSTRACT FROM AUTHOR]

Children with hemophilia usually have recurrent joint bleeding that leads to joint damage, loss of range of motion, and restriction of mobility, therefore affecting the quality of life in these children. The purpose of this study was to compare the effects of low-level laser therapy (LLLT) to that of pulsed electromagnetic field (PEMF) in treatment of hemarthrosis in children with hemophilia. Thirty boys with hemophilia A with ages ranging from 9 to 13 years were selected and assigned randomly, using sealed envelopes, into two equal intervention groups. The study group I received the traditional physical therapy program in addition to LLLT, whereas the study group II received the same physical therapy program given to the study group I in addition to PEMF. Both groups received the treatment sessions three times per week for three successive months. Pain, laboratory investigations, swelling, and range of motion (ROM) of the affected knee joint, in addition to physical fitness were evaluated before, at the end of the sixth week and at 12 weeks of the treatment program. Laser group showed significant improvement in all measured variables after the sixth week of treatment when compared with PEMF. By 12 weeks of treatment, there was a significant improvement in pain, ROM, ESR and leucocytes levels in laser group compared with PEMF, while there was no significant difference in knee circumferences and the 6-min walk test (6MWT) between both groups. Both groups showed significant improvement at 12 weeks of treatment compared with that at 6 weeks. Both LLLT and PEMF are effective modalities in reducing pain, swelling, increasing ROM and improving physical fitness. Twelve weeks of treatment of both modalities demonstrated significant improvement than 6 weeks of treatment. Laser therapy induced significant improvement than electromagnetic therapy in treatment of hemarthrosis-related problems in children with hemophilia. [ABSTRACT FROM AUTHOR]

Background: Prerequisite for management of a chronic disease involves knowledge about its complications and their prevention. Hemophilia in adolescents influences all the aspects of their lives and thier performance. Objectives: The present study aimed to determine the performance of Iranian hemophilic adolescents in prevention of disease complications. Patients and Methods: In this descriptive‑analytical study, 108 adolescents with hemophilia were selected through convenience sampling. Their performance in preventing the complications of hemophilia was evaluated by sending a semi-structured questionnaire to their addresses throughout Iran. Then, the data was analysed using the Statistical Package for Social Sciences (SPSS) software (v. 13) and descriptive and interferential statistics were used. Results: Overall, 32.1% of the participants controlled bleeding during the 1st hour. Inaccessibility of coagulation products was mainly responsible for inhibiting timely and proper bleeding control. In order to relieve bleeding associated pain, only 39.0% of the adolescents used analgesics. On the other hand, 19.8% of the subjects used nonpharmacological methods to relieve pain. The majority of the adolescents did not participate in sport activities (65.4%) others allocated less than 5 hours a week to physical activities (70.5%). In addition, the participants did not have favorable dietary patterns, exercise habits, and dental care. The results showed a significant relationship between the adolescents' preventive practice with coagulation disorders and utilization of pharmacological pain relief methods. Also, significant relationships were found between severity of the disease; participating in physical activities, number of hours of physical activities; and disease complications. Conclusions: Iranian adolescents did not exhibit favorable practices towards complication prevention. [ABSTRACT FROM AUTHOR]

The greatest barrier to successful haemophilia A care in resource-rich countries is the development of inhibitors to therapeutic factor VIII. Children with inhibitors suffer through increased bleeding and joint damage as well as frequent venepuncture. Costs associated with inhibitors are beyond many healthcare systems. Over the last two decades, there has been no improvement in our ability to reduce inhibitor development. Current strategies based on early prophylaxis and avoidance of immunological danger signals have given rise to conflicting results. Registry data suggest an increasing problem. Our understanding of the immunological systems involved in inhibitor formation should inform efforts to prevent inhibitors. Great efforts with mouse models are being undertaken in this field. However, there is no guarantee of the availability of any new agents arising from experimental work in the near future. Global immunomodulatory agents may be one solution. Compounds with a long history of use in inflammatory conditions have demonstrated efficacy in preventing antibodies to protein therapeutics both in animal models and in humans. As these compounds have a long history of use in humans, including babies, it may be that these agents offer an option for reducing inhibitor formation in previously untreated patients. [ABSTRACT FROM AUTHOR]

The use of pulsed ultrasound (PUS) and low level laser therapy (LLLT) in patients with haemophilia has been recommended for supportive treatment of acute and chronic phases of haemarthrosis but its role has not been supported by experimental evidence. The purpose of the present study was to evaluate the effect of these modalities on joint swelling, friction and biomechanical parameters of articular cartilage. An experimental rabbit knee haemarthrosis model was used to test the hypothesis that LLLT and PUS favourably impacted on the biotribological and biomechanical properties of cartilage after joint bleeding. To test this, 35 male albino rabbits weighing 1.5-2 kg were used. The left knee of 30 rabbits was injected with 1 mL of fresh autologous blood two times per week for four consecutive weeks to simulate recurrent haemarthrosis; five rabbits served as non-bleeding controls. Ten rabbits were treated with PUS and 10 with LLLT and the remaining 10 were not treated. The treatments were started after 2 days and the treatment duration was planned for 5 days (sessions) in ultrasound and laser groups. A low level Ga-Al-As laser was applied with an 810 nm wavelength, 25 mW power, and 1 J cm−2 dosage for 200 s duration. The PUS treatment was applied with a duty cycle of 1/9, frequency of 1 MHz, and power of 0.4 W cm−2 for 150 s. Joint perimeter was measured before the procedure at the beginning of therapies and after cessation of the procedure. Friction and biomechanical parameters were measured immediately after the killing of the animals. The results demonstrate that PUS was more effective in reducing knee joint swelling than LLLT. Moreover, PUS had the unique ability of reducing the joint friction below normal values. However, it was not successful in returning the articular cartilage force and stiffness to normal state. LLLT was more effective in increasing equilibrium force of the articular cartilage than PUS, however, neither therapy normalized this parameter. From these data, we conclude that PUS is more effective than LLLT in reducing joint swelling and articular joint friction after experimental haemarthrosis. [ABSTRACT FROM AUTHOR]

Objective: To assess the hemostatic efficacy of a new local hemostatic agent, Ankaferd Blood Stopper (ABS), for the control of bleeding following tooth extraction in hemophiliacs. Materials and Methods: Simple tooth extractions were performed in 27 hemophilia A patients. In the treatment group (n=17) local hemostasis was achieved via application of ABS to the extraction sockets, whereas in the control group (n=10) local hemostasis was achieved via direct packing with gauze. Results: In all, 57 (21 primary and 36 permanent) teeth extractions were performed in 27 hemophilia A patients. There were no significant differences in age or factor VIII level distribution between the 2 groups (p>0.05). The most significant clinical difference between the groups was associated with the use of ABS; those in the treatment group had significantly shorter duration of bleeding (p=0.002). Conclusion: This is the first study to evaluate the efficacy of ABS for the control of bleeding following tooth extraction in hemophiliacs. ABS can be considered an alternative local hemostatic agent for reducing clotting factor concentrates in hemophilia patients. [ABSTRACT FROM AUTHOR]

Haemophilic arthropathy of the ankle causes pain and deterioration in gait, causing disability. Although some physiotherapy modalities are effective in the management of acute bleeding, the results are unknown in chronic arthropathy. Our objective was to determine the most effective physiotherapy procedures for treating the haemophilic arthropathy of the ankle and to assess the methodological quality of the studies. A systematic review was carried out in the CochraneDatabase, PubMed,MEDLINE, ISIWeb of Knowledge, PEDro, TESEO, and specialized journals (Haemophilia and Haematologica). It included articles with at least one group undergoing any kind of physiotherapy treatment and with pretest and posttest evaluation, published before April 2013. An analysis of variables was performed and assessed the methodological quality of studies. Five studies met the criteria for inclusion. Hydrotherapy treatments, strength training and balance strength, balance training, and sports therapy, have improved range of movement, pain, balance, and subjective physical performance.The proposed methodological analysis was not possible due to the low quality of the studies. Although the results are positive, they lack rigorous evidence on the effects of treatments. Studies are needed to establish the efficacy of the various forms of physiotherapy in the haemophilic arthropathy of the ankle. [ABSTRACT FROM AUTHOR]

. Haemophilic arthropathy (HA) is one of the main complications of recurrent bleeding episodes in patients with severe haemophilia. However, the precise reasons making joints the predilected site of bleeding in patients with haemophilia are not fully understood. The objective of this project was to study the potential effect of synovium-derived thrombomodulin (TM) on the pathophysiology of haemarthroses. The concentration of TM and tissue factor pathway inhibitor (TFPI) was measured in knee synovial fluid of patients with haemophilia and controls. We used these concentrations of TM and TFPI in a thrombin generation (TG) model to analyse their in vitro effects on coagulation in plasma of six male controls and six severe haemophiliacs. The expression of TM in synovial tissue was also studied in controls and haemophiliacs. Patients with HA had significantly higher synovial fluid TFPI and TM levels, with a mean of 47 ± 27 ng/mL ( P = 0.033) and 56 ± 25 ng/mL ( P = 0.031), respectively, compared to the control group which presented lower levels of synovial fluid TFPI (26 ± 9 ng/mL) and TM concentrations (39 ± 21 ng/mL). TG capacity was significantly reduced in the presence of TM 56 ng/mL ( P = 0.02), concentration observed in the synovial fluid of patients with HA. The concomitant addition of TM 56 ng/mL and TFPI 47 ng/mL induced a highly significant inhibition of TG in the same samples ( P = 0.008).No significant inhibition of TG capacity was observed in the presence of control synovial concentration of TM ( P > 0.05). Our results showed increased TM levels in synovial fluid and dramatically impaired expression of TM on synovial cells, suggesting a massive release of TM into the synovial fluid induced by a concerted action of neutrophils and cytokines on synovial cells as previously described in patients with rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

The article focuses on the causes, treatment and complications of hemophilia. Hemophilia is caused by a deficiency of clotting factors. Prompt treatment of bleeding episodes is necessary to prevent the complications of joint or muscle damage. Treatment involves the replacement of the deficient factor through agents such as desmopressin. The use of antifibrinolytics is discussed.

Background. People with bleeding disorders may develop severe arthritis due to joint hemorrhages. Exercise is recommended for people with bleeding disorders, but guidelines are vague and few studies document efficacy. In this study, 65% of people with bleeding disorders surveyed reported participating in minimal exercise, and 50% indicated a fear of exercise-induced bleeding, pain, or physical impairment. Objective. The purpose of this study was to examine the feasibility, safety, and efficacy of a professionally designed, individualized, supervised exercise program for people with bleeding disorders. Design. A single-group, pretest-posttest clinical design was used. Methods. Thirty-three patients (3 female, 30 male; 7--57 years of age) with mild to severe bleeding disorders were enrolled in the study. Twelve patients had coexisting illnesses, including HIV/AIDS, hepatitis, diabetes, fibromyalgia, neurofibromatosis, osteopenia, osteogenesis imperfecta, or cancer. Pre- and post-program measures included upper- and lower-extremity strength (force-generating capacity), joint range of motion, joint and extremity circumference, and distance walked in 6 minutes. Each patient was prescribed a 6-week, twice-weekly, individualized, supervised exercise program. Twenty participants (61%) completed the program. Results. Pre- and post-program data were analyzed by paired t tests for all participants who completed the program. No exercise-induced injuries, pain, edema, or bleeding episodes were reported. Significant improvements occurred in joint motion, strength, and distance walked in 6 minutes, with no change in joint circumference. The greatest gains were among the individuals with the most severe joint damage and coexisting illness. Limitations. Limitations included a small sample size with concomitant disease, which is common to the population, and a nonblinded examiner. Conclusions. A professionally designed and supervised, individualized exercise program is feasible, safe, and beneficial for people with bleeding disorders, even in the presence of concomitant disease. A longitudinal study with a larger sample size, a blinded examiner, and a control group is needed to confirm the results. [ABSTRACT FROM AUTHOR]

Hemophilic pseudotumor (HP) is rare, seen in 1-2% of patients with hemophilia, and is extremely uncommon in the mandible. A 6-year-old boy with moderate hemophilia A presented to our hospital with left mandibular swelling. Based on clinical and radiological findings, a tentative diagnosis of HP was made. After factor VIII administration, the lesion was curetted and HP was confirmed on histopathology. The patient was treated with twice-weekly factor VIII until the lesion had completely resolved and bone had regenerated at 1 year. The best treatment for HP is not established; however, appropriate initial treatment and postoperative prophylaxis are effective. [ABSTRACT FROM AUTHOR]

The ankle joint is well known to show early involvement in severe haemophilia. We describe a novel operative technique developed by the senior author. This combines a medial approach to the ankle, medial malleolar osteotomy, bone graft and compression with staples. All patients had excellent pain relief and improvement in function with 100% achieving bony union. There was a significant improvement in Mazur ankle scores following ankle fusion ( P < 0.01). This surgical technique gives good results which are reproducible in this patient population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The optimal on-demand treatment of joint bleeds in haemophilia patients with inhibitors is a source of debate, with studies reporting various efficacy levels for different drugs and dosage regimens. To analyse, in a unified Bayesian meta-regression model, the published efficacy of recombinant activated factor VII (rFVIIa) and/or activated prothrombin complex concentrate (aPCC) as on-demand treatments for joint bleeds in haemophilia patients with inhibitors. A systematic search was carried out to identify studies reporting on dosage and efficacy of rFVIIa and aPCC in the treatment of joint bleeds in the target patient population. Data were abstracted and included in the model and adjusted for potential sources of heterogeneity. Pooled efficacy levels for typical rFVIIa and aPCC regimens were estimated. Seventeen studies, collectively reporting on >2000 joint bleeds, were included. Medication type combined with dosage was the only significant explanatory parameter. The model predicts that a typical regimen of 90 μg kg−1 rFVII repeated every 3 h if needed results in cumulative joint bleed resolution of 66%, 88% and 95% after 12, 24 and 36 h, respectively. In comparison, a typical regimen of 75 IU kg−1 aPCC repeated every 12 h if needed results in cumulative joint bleed resolution of 39%, 62% and 76%, respectively. These differences were statistically significant and were also robust in sensitivity analyses. This analysis suggests that a typical rFVIIa regimen will resolve joint bleeds more effectively than a typical aPCC regimen after 12, 24 and 36 h. [ABSTRACT FROM AUTHOR]

Recombinant factor VIIa (rFVIIa) is a pro-haemostatic agent that is effective in the treatment of bleeding in haemophilia complicated by inhibitors and some other haemorrhagic disorders. The rFVIIa product promotes haemostasis in these settings by enabling the rapid generation of thrombin on the surface of activated platelets which increases fibrin deposition. rFVIIa also has therapeutic activity in bleeding in platelet function disorders such as Glanzmann's thrombasthenia and thrombocytopenia. This suggests that rFVIIa also has a pro-haemostatic effect on platelets and this may contribute to the overall therapeutic action of this agent. The effects of high-concentration FVIIa on platelets have been studied in detail in experiments using ex vivo model systems of haemostasis under static and flow conditions. These experiments show that FVIIa potentiates multiple functional markers of platelet activation and this effect requires direct binding of FVIIa to the activated platelet membrane and the generation of thrombin. The mechanism of this potentiating effect of FVIIa on platelet activation is complex and is likely to require multiple platelet activation receptors and signalling pathways. These include the GPIb-IX-V glycoprotein complex and the thrombin protease activated receptors. The proposed mechanism of action of high-concentration FVIIa has important implications for the therapeutic activity of rFVIIa in vivo. This review summarizes the clinical and experimental evidence supporting a potentiating effect of FVIIa on platelet activation and discusses the likely mechanism of action. [ABSTRACT FROM AUTHOR]

BACKGROUND: Chronic hemophilic synovitis of the elbow usually leads to enlargement and erosion of the radial head, resulting in mechanical blockage of forearm rotation, synovial impingement, recurrent hemarthrosis, and pain. The purpose of the present study was to evaluate the intermediate-term results of radial head excision and synovectomy in a large group of patients with hemophilia who had been managed at a single institution. METHODS: Information on forty radial head excision and synovectomy procedures that had been performed at our institution from 1969 to 2004 was retrospectively collected. All but one of the operations had been performed in patients with severe hemophilia. The mean age of the patients at the time of the procedure was thirty-three years. Pain, limited range of motion, and bleeding were the indications for surgery. The mean duration of follow-up was 7.7 years. RESULTS: Only one postoperative complication was observed: a posterior interosseous nerve palsy that fully resolved by six months. No additional surgical intervention for bleeding was required in sixteen of the nineteen elbows in which bleeding was one of the indications for surgery. Of the forty elbows, seven required a secondary surgical procedure at a mean of five years after the excision of the radial head. Examination of the mean range of motion at the time of the latest follow-up demonstrated a 63° increase in the pronation-supination arc (p < 0.00001) but only a 2° increase in the flexion arc. CONCLUSIONS: Radial head excision in patients with hemophilia is an effective procedure for improving forearm rotation and reducing pain and bleeding frequency, with a low risk of complications. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Lysosomal storage diseases are characterized by deficiencies in lysosomal enzymes, allowing accumulation of target substrate in cells and eventually causing cell death. Enzyme replacement therapy is the principal treatment for most of these diseases. However, these therapies are often complicated by immune responses to the enzymes, blocking efficacy and causing severe adverse outcomes by neutralizing product activity. It is thus crucial to understand the relationships between genetic mutations, endogenous residual enzyme proteins (cross-reactive immunologic material), development of neutralizing antibodies and their impact on clinical outcomes of lysosomal storage diseases. For patients in whom neutralizing antibodies may cause severe adverse clinical outcomes, it is paramount to develop tolerance inducing protocols to preclude, where predictable, or treat such life-threatening responses. [ABSTRACT FROM AUTHOR]

The development of inhibitory alloantibodies to factor VIII (FVIII) is a major complication of clotting factor replacement therapy for hemophilia A. Inhibitor development compromises effective hemostasis management in affected individuals and results in higher morbidity and costs of care compared with hemophilic individuals without anti-FVIII antibodies. The therapeutic approach to the management of bleeding in the presence of low- and high-titer inhibitors is founded on the principles of either saturating antibody with excess FVIII or bypassing the FVIII requirement altogether. Although spontaneous antibody disappearance does occur, immune tolerance is often required for antibody eradication. Studies aimed at optimizing this treatment approach and developing newer strategies for inhibitor prevention are ongoing. [ABSTRACT FROM AUTHOR]

Objective: To report the use of extracorporeal membrane oxygenation (ECMO) as a bridge to cardiac transplantation in a patient with hemophilia A and dilated cardiomyopathy.Design: Case report.Interventions and Results: During ECMO factor VIII concentrate was administered to maintain a factor VIII level close to 50% of normal control both to decrease the risk of bleeding and to allow standard anticoagulation with heparin. The patient developed an inhibitor to exogenous factor VIII during hospitalization, which was successfully managed with a high-dose continuous infusion of factor VIII during ECMO, the transplant operation, and the postoperative period.Conclusions: We report the successful use of ECMO as a bridge to cardiac transplantation in a patient with hemophilia A and low-level factor VIII inhibitors. [ABSTRACT FROM AUTHOR]

Summary. Chronic proliferative synovitis secondary to haemathroses is a major complication in patients with severe haemophilia. Current management strategies include prophylactic infusions of the missing coagulation factor, corticosteroids, synoviorthesis and/or synovectomy with variable degrees of benefit. In addition, patients with coagulation factor inhibitors are not amenable to the invasive therapeutic modalities. The gross and microscopic findings of the synovitis in haemophilic arthritis are remarkably similar to those seen in patients with rheumatoid arthritis, although the pathophysiology of these two conditions are quite different. Haemophilic arthropathy, in the later stages, resembles degenerative rather than inflammatory joint disease. Oral d-penicillamine, a drug effective in the proliferative synovitis of rheumatoid arthritis, was evaluated in 16 patients. Ten patients had an unequivocal response, while three had a reduction in palpable synovium and three had no response. Thus 81% of the patients had a beneficial response. Minor reversible drug side-effects occurred in two patients (proteinuria in one and a rash in the second). The results of this study suggest that d-penicillamine is an effective and safe drug for the treatment of haemophilic chronic synovitis. [ABSTRACT FROM AUTHOR]

The development of arthropathy is a serious complication of severe haemophilia. With the use of prophylaxis, bleeds can be prevented and arthropathy delayed. We investigated whether an individually tailored prophylactic regimen can prevent arthropathy and whether it had a similar effect on orthopaedic outcome compared with that of a high-dose regimen. Efficacy was determined clinically and by radiographs of six major joints. Prophylaxis was started in 70 patients at a mean age of 4·1 years. Mean follow-up was 15·6 years (range 8–24·5 years). The mean factor VIII consumption was 2319 IU/kg/year. The mean number of joint bleeds was 3·5/year and the mean clinical score (maximum score 90) was 1·0, with a mean Pettersson joint score (maximum score 78) of 3·0 at a mean age of 13·5 years. In conclusion, long-term, early-onset, individualized prophylaxis in haemophilia is feasible and prevents arthropathy. [ABSTRACT FROM AUTHOR]

Examines the progression of HIV diseases in a hemophilic cohort and the effect of treatment. Treatment with zidovudine or placebo; Symptoms of HIV infection, AIDS and death; Estimation of the rate of progression.

A haeophilic pseudotumour is a rare complication of Haemophilia occurring in 1–2% of patients with a factor VIII or IX deficiency. This report presents three surgical cases of pseudotumours involved in a pathological fracture in the extremities. All cases showed a favourable post-operative course. If the preoperative management is appropriately designed, a limb salvage operation for a pathological fracture due to a pseudotumour could be carried out successfully. Before choosing amputation of a limb, the surgeon should consider the possibility of limb salvage. [ABSTRACT FROM AUTHOR]

Copyright of International Orthopaedics is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A 27-year-old previously healthy man with hemophilia presented with Pneumocystis carinii pneumonia. The patient had several episodes of oral candidiasis followed by disseminated infection with Mycobacterium avium-intracellulare. He was not homosexual nor did he take illicit drugs, but he had been self-administering two to four monthly infusions of factor VIII concentrate for 7 years. In-vitro lymphocyte studies showed findings consistent with the acquired immunodeficiency syndrome that had previously been reported only in homosexual men, drug addicts, and Haitian refugees. The cause of this syndrome is unknown, but the possibility that it is associated with a transmissible agent acquired through the use of blood products such as factor VIII concentrate must be considered. [ABSTRACT FROM AUTHOR]

Provides information on a study that documented urinary loss of factor IX as a potential cause for factor IX deficiency in a patient with the nephrotic syndrome. Methodology of the study; Results and discussion on the study.

The combination of interferon (IFN) and ribavirin is the current gold standard for treatment of chronic hepatitis C virus (HCV) infection with sustained remission rates of 35–40% being achieved in haemophilic patients. A similar beneficial effect of this combined therapy has been suggested even for patients with compensated liver cirrhosis and some authors have reported a possible role for IFN and ribavirin in the prevention or delay in the development of hepatocellular carcinoma (HCC), a well known complication of HCV infection in haemophiliacs. The absence, due to design difficulties, of definite randomized controlled clinical trials remains a handicap for the routine use of specific therapy of HCV infected patients with the aim of preventing HCC. A discussion of these important issues has been performed in this paper. [ABSTRACT FROM AUTHOR]