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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Haemophilia 9 (2003), S. 0 
    ISSN: 1365-2516
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Synoviorthesis is the intra-articular injection of chemical or radioactive substances able to produce fibrosis of hypertrophied synovium, which has proved effective in the treatment of chronic haemophilic synovitis. Between September 1999 and October 2001 we treated 28 outpatients (25 with haemophilia A, three with haemophilia B). Our treatment was focused on pain and functional limitation of joints. A schedule was adopted to treat each joint using intra-articular rifamycin once a week, repeated five times. Patients were covered with factor replacement on demand. Oral analgesia was offered as required because of acute but transient painful inflammatory reaction. Their median age was 34 years (range 15–60 years). The indication for synoviorthesis was chronic synovitis characterized by recurrent haemarthroses, persistent pain and limited range of motion (ROM). Thirty-five joints were treated with a total of 169 injections, including six joints (20%) in patients with inhibitors. In five patients two joints were treated in the same session. Thirty procedures were completed: 24 (80%) were considered effective (as excellent or good), while six were considered insufficient (20%). Pain was reduced in 96% of cases and in 70% the ROM was improved. In our experience intra-articular infiltration with rifamycin appears to be effective in reducing joint pain and in improving the ROM. The procedure presents a low risk of bleeding, can be used for patients with inhibitors and multiple joints can be treated without any additional cost.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-2516
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary.  The introduction of activated recombinant factor VIIa (rFVIIa) has allowed elective surgery to be safely performed in haemophiliacs with inhibitors. The main problems associated with its use are the short half-life, necessitating frequent intravenous injections, and its very high cost. Here we describe, for the first time, the performance of total hip and knee replacements in a haemophiliac with inhibitors at the same operation. The amount of rFVIIa concentrate used (8.57 mg) was similar to that normally used for a single joint replacement. The use of continuous infusion allowed for easier administration and further contributed to the reduction in cost as it avoids the peak levels associated with bolus injections.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Haemophilia 10 (2004), S. 0 
    ISSN: 1365-2516
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1365-2516
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Haemophilia A displays a broad heterogeneity of genetic defects and of clinical severity. Inhibitor development is the main complication of replacement therapy in severe cases and most patients with inhibitors have gross gene rearrangement or point mutations, which hamper the production of normal circulating factor VIII (FVIII). We have investigated three related severe haemophilia A patients, all of whom have high titre inhibitors. By using long-range polymerase chain reaction (PCR) for FVIII gene inversion, we observed an unusual pattern in these patients. We therefore decided to screen the whole FVIII gene by conformation-sensitive gel electrophoresis. A large FVIII gene deletion spanning exon 2 to exon 25 was identified and we were able to obtain a 18.5 kb PCR product, which is specific for this mutation and useful for determining the carrier state in this family. All three haemophiliacs carrying this very large gene deletion show similar clinical history and very high-titre inhibitors, supporting the observation that inhibitor development seems to be an inherited characteristic. On the basis of our observations we think that this subgroup of patients at very high risk of inhibitor development should be identified by mutation analysis whenever possible, before the beginning of replacement therapy.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford UK : Blackwell Science Ltd
    Haemophilia 7 (2001), S. 0 
    ISSN: 1365-2516
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1365-2516
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Haemophilia B patients with factor IX (FIX) activity 〈 1% are usually characterized by severe bleeding episodes early in life. We report a case of sporadic severe haemophilia B, clinically characterized by mild bleeding diathesis. The presence of anamnestic thrombophlebitis in the patient’s mother prompted us to investigate a possible associated hypercoagulable condition. Resistance to activated protein C due to factor V R506Q mutation was present in the mother and in the propositus, in the homozygous and heterozygous form, respectively. Molecular analysis of the FIX gene led to the identification of a nonsense mutation resulting in a stop codon at position 50, previously described and usually responsible for a severe pattern of haemophilia B. The implications of this unusual association are discussed.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Haemophilia 10 (2004), S. 0 
    ISSN: 1365-2516
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary.  We present 11 cases of surgery in haemophilia patients with inhibitors (high responders). They were: one haemorroidectomy, one vesical surgery in a high responder, one adenoidectomy, seven orthopaedic procedures (one bone fixation of a femoral neck fracture, four total knee arthroplasties, two total knee arthroplasties), and one retroperitoneal haematoma that required emergency surgery. We conclude that surgery in haemophilia patients with inhibitor can be considered feasible but nevertheless remains difficult. When applied to high-responding patients the treatment must take into account both the haemorrhagic risk and the risk of anamnestic response. Use of activated fractions as first-line therapy makes it possible (if the titre of the antibody allows it) to resort to conventional replacement therapy with FVIII or FIX concentrates. NovoSeven® or FEIBA® can be equally used as first-line therapy including therapy for major surgeries. It can be useful to alternate one with the other in case of occurrence of haemorrhagic complications.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1365-2516
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary.  Participants in an international workshop on surgery in haemophilia patients with inhibitors developed a consensus summary of the findings and conclusions of the meeting. In the consensus, participants agreed upon revised definitions for minor and major surgery, including an intermediate degree of surgery. An evaluation system of intraoperative and postoperative bleeding was developed. Recommended doses of FEIBA® and rFVIIa (both in bolus injections and in continuous infusion) for surgery were agreed. Participants also agreed on the main blood tests to be performed peri-operatively. They also suggested the need of a prospective evaluation in the future. Finally, the approximate number of surgical procedures and costs performed on haemophilia patients with inhibitors were analysed.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1365-2516
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary.  Patients with haemophilia show high prevalence of hepatitis C infection but low rate of progressive liver disease when they are not co-infected with HIV. The balance between host immune system and hepatitis C virus (HCV) variability seems to play a major role in the evolution of the HCV-related disease. To address this point we have studied, in a group of selected patients with haemophilia, the composition and in some cases the evolution, of the highest variable envelope gene within the hypervariable region 1 (HVR1) of the HCV, which is the region more directly exposed to the host immune response. Five of 12 patients show a very high homogeneity of the HVR1 and four of those had severe progressive liver disease. These results seem to confirm the major role of the immunity in driving the variability of the HCV rather than the high degree of different HCV strains to which haemophiliacs have been in touch with, during their long-term replacement therapy. Our results seem in keeping with other studies on different type of patients, where a low degree of quasispecies variability has been demonstrated in relationship with the progression and the severity of their liver disease.
    Type of Medium: Electronic Resource
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