ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00134.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.Non‐Hodgkin's lymphoma is the most common malignancy in individuals with haemophilia and human immunodeficiency virus (HIV) infection. Among individuals with haemophilia, lymphoma accounts for 5% of primary AIDS diagnoses, and it is the sixth most common primary AID‐defining diagnosis in this group. At the time of AIDS‐lymphoma diagnosis, the median age in haemophiliacs is 32 years, the mean CD4 count is 116 μL−1, and the mean time from seroconversion to development of AIDS‐lymphoma is 8 years. The most common primary site of AIDS‐lymphomas in haemophiliacs is the gastrointestinal tract, and the most common histological type is large cell lymphoma. EBV has been detected at a molecular level in half of all haemophilia AIDS‐lymphomas and its presence is predictive of shorter survival than in those without detectable EBV. The median survival after diagnosis is 6 months, with or without treatment. An increasing proportion of these tumours are occurring as secondary AIDS diagnoses, associated with the longer duration of immunosuppression afforded by antiviral therapy. This paper reviews the natural history, immunological and viral features, clinical characteristics, and risk factors associated with AIDS‐lymphoma in the haemop

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00135.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.Approximately one‐third of haemophilia B cases are described as isolated due to their occurrence in families with no prior history of the disorder. In this report, two families with isolated haemophilia B were studied by the standard method of restriction fragment length polymorphism (RFLP) analysis coupled with factor IX activity and antigen levels with the aim of achieving carrier diagnoses. The limitations of using this approach in the determination of carrier status were highlighted by diagnostic problems arising in both families. The problems included difficulty in interpreting bioassay results, homozygosity for the RFLP marker in a key family member and the possibility of germline mosaicism. Unequivocal carrier diagnosis in the two families was ultimately achieved by direct mutation analysi

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00136.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.To describe the patterns of bleeding and clotting factor concentrate use in boys with haemophilia over a 6‐month period, daily diary records of bleeding, factor use, levels of physical activity, chore performance and school attendance were collected from parents of 96 males between 4 and 17 years of age with haemophilia A or B followed at six comprehensive haemophilia treatment centres in Massachusetts, Rhode Island and Tennessee. 14 243 person days were available for analysis. The sample cohort averaged approximately nine bleeding episodes (1.5 per months), almost two‐thirds of which were haemarthroses. 44% of bleeds were associated with injury and the average duration was 1.4 days. New bleeding episodes were significantly more likely to begin on weekdays (Monday–Thursday) than on weekends (Friday–Sunday). Boys with more severe disease had significantly more bleeding episodes and a higher frequency of haemarthroses. Boys with the most severe disease were also more likely to have joints involved when they bled and to have more spontaneous bleedings without apparent preceding trauma. Bleeding was associated with increased school absence, decreased levels of physical activity and decreased rates of household task performance. Relatively high rates of bleeding associated with trauma suggest the need for preventive interv

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00137.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.Administration of factor VIII (F VIII) concentrates by continuous infusion is now routinely used at several haemophilia centers but almost exclusively for hospitalized patients. We evaluated various aspects of home therapy with continuous infusion of an immunoaffinity purified F VIII concentrate (Monoclate P®, Armour) in patients who would normally have been treated with high doses in bolus injections or with continuous infusion as in‐patients. Twenty haemophilia A patients, eight after minor surgery and 12 for serious haemorrhage, received continuous infusion with undiluted F VIII by a minipump for a mean of 0.9 days in the hospital, followed by 3.3 days at home. Infusion bags were exchanged every 2.5 days. No haemorrhagic complications occurred, and five haemorrhages that had been resistant to treatment with bolus injections responded promptly to the continuous infusion. There were no technical problems and patient compliance and acceptance was good. We find this mode of therapy safe, efficacious and convenient for the patients as well as for the sta

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00138.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.Fifty consecutive haemophiliacs were entered into a pilot study of socioeconomic impact of haemophilia treatment. The Short Form 36 was used as an instrument for the assessment of quality of life. Direct and indirect costs were analysed. Incremental cost‐effectiveness was expressed as additional costs per joint bleed avoided by prophylactic treatment over on‐demand treatment. Thirtynine patients (mean age 35.14 years) were substituting factor VIII according to an on‐demand and 11 patients according to a modified prophylactic regimen. There were an average of 9.84 joint bleeds per patient across all patients during the 6‐month observation period: on‐demand group 10.74 bleeds, prophylactic group 6.64 bleeds. This difference was not statistically different. Significant differences between haemophiliac patients and healthy men were seen in the assessment of their limitations of physical activities, limiting pain and general health. The total cost per patient during the 6 months was DM 24 601 in all patients, DM 17 253 in those on an on‐demand base and DM 28 245 in the modified prophylactic group. Patients experienced an average 4.71 days off work: on demand 5.81 days, prophylactic regimen 0 days. The total indirect cost per patient was DM 683; therapy cost per patient was DM 25 284; cost per avoided bleed DM 1680 for on‐demand therapy and DM 4228 on prophylaxis. The incremental cost‐effectiveness, i.e. the additional costs to avoid one additional joint bleed by prophylactic treatment, was DM 2536. In conclusion, patients receiving prophylactic clotting factor therapy require less additional health care resources, mainly due to the reduction in the number

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00139.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.The laboratory assessment of von Willebrand factor (VWF) is typically performed at specialist laboratory sites, particularly when performed as a battery of laboratory tests in a thorough workup for the diagnosis of von Willebrand's disease (VWD). In these cases, specimens could derive from a variety of off‐site sources, including smaller laboratories, and general clinical practitioners. Because of the potential for lack of control by the specialist laboratory over the method of specimen handling and transport from these sources, and recent VWF methodological advances, we investigated the effect of prolonged ambient temperature specimen storage on laboratory assay results. Thus, specimens were collected from 10 separate individuals, and each variably processed to provide an ideal (‘control') plasma specimen, and additional specimens that were then stored at ambient temperature for up to 7 days. Specifically, specimens were stored either as whole blood, or as separated plasma, and VWF tested in isolated plasma, post 24 h, post 48 h and post 7 days storage. Three separate laboratory assays for VWF were performed; (i) a standard ‘antigen’ (antisera‐ELISA‐based) assay (VWF:Ag), (ii) a standard ristocetin‐dependent‐platelet‐agglutination procedure (VWF:RCof) and (iii) a more recently described ELISA‐based functional collagen‐VWF binding assay (VWF:CBA). Results can be summarized as follows, (i) Plasma storage: there was no (statistically significant) change in VWF:Ag or VWF:RCof assay results over the 7‐day storage period; however, there was a small but statistically significant fall (P= 0.009) in VWF:CBA assay results after 7 days storage of plasma. (ii) Whole blood storage: there was no (statistically significant) change in VWF:Ag, VWF:CBA or VWF:RCof assay results over the 7‐day storage period, although the data suggested a trend towards increasing VWF:Ag over time. As a result of the change in assayed VWF:CBA following prolonged plasma storage, a similar small but statistically significant (P= 0.009) change (increase) in the VWF:Ag to VWF:CBA ratio was observed. This ratio has previously been determined to be useful in the differential diagnosis of VWD subtypes, with high VWF:Ag to VWF:CBA ratios potentially indicative of Type 2 VWD. Fortunately, the absolute magnitude of the altered ratio following prolonged plasma storage is unlikely in practice to affect the diagnosis of VWD in most testing cases. Nevertheless, there will be occasional borderline normal cases in whom the change in VWF:CBA, or in the calculated VWF:Ag to VWF:CBA ratio, may otherwise influence a clinical diagnosis of VWD. Caution is therefore suggested in the interpretation of laboratory‐derived VWF data, particularly if the specimen is deri

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00140.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.In 1993–94, 15 high responders were treated in our centre according to the Malmo protocol which was modified as follows: serial plasmapheresis was performed instead of extracorporeal adsorbtion to protein A for reducing inhibitor levels and, after the bolus dose to neutralize the inhibitor, factor VIII concentrate was administered by a continuous infusion. Thus, this regimen included continuous infusion of factor VIII(FVIII) for 1–4 weeks, iv cyclophosphamide for 2 days and orally for 8–10 days, and intravenous immunoglobulin (IVIG) from the fourth day for 5 days. All patients had been qualified for the treatment when the antibody level was<15 BU mL−1. Tolerance was induced in 10 patients (66.6% very good and good results). The treatment failed in five cases in which, due to a high inhibitor level, it was not possible to maintain a measurable factor VIII:C concentration throughout the whole period of infusion. We compared these results with results of our low‐dose regimen: 25 IU FVIII kg−1b.w. twice a week (1985–89, 11 high responders). The modified Malmo Protocol is much shorter than the low‐dose programme and this is a method of first choice in patients undergoing surgery in

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00141.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.To assess the effect of HIV infection and the introduction of virus‐inactivated concentrates, we conducted a retrospective 20‐year longitudinal study of hepatitis B virus (HBV) serology and look for HBV DNA in recent serum samples of 63 multiply transfused haemophiliacs.Of 63 haemophiliacs, 51 had evidence of previous HBV infection and 12 vaccinees had anti‐HBs only. Of 40 HIV‐negative, two had persistent HBsAg but all were HBV DNA negative. All 23 HIV‐positive were HBsAg‐negative. Loss of anti‐HBc(46% vs. 17.5%) and anti‐HBs (32% vs. 14%) was more commonly seen in HIV‐infected compared with noninfected individuals. One HIV‐positive individual had HBV DNA detectable by PCR. Restrospective testing demonstrated that re‐emergence was associated with loss of anti‐HBs and advanced HIV infection (CD4<50 × 106–1L CDC II), although eight other with CDC IV disease were HBV DNA negative.Forty‐three batches of concentrates produced between 1965 and 1992 from both commercial and volunteer donors and subjected to different donor screening and virus inactivation methods were negative for HBV DNA. Some of these may have been infectious for HBV and therefore being negative for HBV may not equate with noninfectivity.We conclude that both HIV‐positive and ‐negative haemophiliacs have lost protective antibodies against HBV since 1984 and that virus replication may re‐emerge at least in the HIV‐positive group. These observations may have implications for the management of their chronic liver disease and the risk of infection of se

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00142.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.The objective was to compare the immunogenicity, reactogenicity and safety of an inactivated hepatitis A vaccine administered subcutaneously to patients with congenital coagulation disorders. Subjects, 97 patients with congenital coagulation disorders (67 men aged>16 and 30 children aged ≤ 16 years), received hepatitis A vaccine administered at 1440 ELISA (enzyme linked immunosorbent assay) units (ELU) to the adult group and at 720 ELU to the child group at 0 and 6 months by the subcutaneous route. The vaccine was well tolerated, with the incidence of adverse events decreasing with subsequent administration of vaccine. Overall, 90% of subjects seroconverted 1 month after the booster (95% confidence interval 76–97%), with 100% seroconversion occurring in the child group compared with 85% in the adult group. There was a corresponding progressive rise in geometric mean titres in each group and no significant difference in the geometric mean titres was found between the two groups. Of the subjects, 29% were HIV positive, 3% of children compared with 40% of adults. A lower rate of seroconversion was observed in subjects with low CD4 counts. Administration of two doses of an inactivated hepatitis A vaccine at 1440 ELU in adults and 720 ELU in children is safe and highly immunogenic when given by the subcutaneous ro

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00143.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY