ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00153.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.The advent of AIDS has had such a deep‐reaching effect on the international haemophilia community that one can make a reasonable distinction between a pre‐AIDS and a post‐AIDS era in haemophilia management. In the context of counselling, however, talking about a ‘before’ and an ‘after’ in haemophilia does not (and, in our opinion, should not) necessarily imply a separation of the past from the present. Dealing with the psycho‐social implications of haemophilia and HIV infection does not mean focusing exclusively on HIV‐generated problems at the expense of haemophilia‐related issues.Since the HIV crisis, counselling has posed the multiple challenge of: (a) assessing and alleviating the more immediate emotional effects of HIV infection; (b) paying due attention to the underlying influence of haemophilia on reaction, defence and coping; (c) formulating a flexible approach that is based on close cooperation with the medical staff and effective interpersonal communication with the counsellees.*In practice, the flexibility and effectiveness of the counselling model are promoted by means of: (a) ongoing counselling, (b) multiple counselling sites (i.e. the Haemophilia Centre and other appropriate locations), (c) interdisciplinary team‐work, (d) respect for individual/ ethnic values, (e) maintenance of exo‐empathy (i.e. neutrality), and (f) transfer of coping skills.The above framework can help maximize the effectiveness of counselling sessions through a personalized rapport of mutual trust and confidence between the counselling t

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00002.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.Carrier detection and prenatal diagnosis of haemophilia A, which was based in the last decade mainly on linkage polymorphism analysis, has been greatly facilitated by the recent discovery that two types of inversion disrupting the factor VIII gene are common mutations observed in 42–48% of severe haemophilia A cases. In this study DNA analysis was performed in 64 unrelated severe haemophilia A patients and 173 women belonging to their families, and in four women from a family with a deceased haemophilic relative whose DNA was unavailable (a total of 177 females from 65 unrelated families). Factor VIII gene inversions were found in 32 out of the 65 families (49%), 29 involving recombination with the distal A gene and three with the proximal A gene. Definitive information regarding carriership of haemophilia was provided to all 81 women belonging to the 32 inversion‐positive families, among them one woman previously uninformative for any of the polymorphisms examined, five women who were informative only for extragenic polymorphisms, and four suspected carriers who were relatives of the deceased haemophiliac. In 33 inversion‐negative families, 96 females were examined by analysis of the BclI restriction fragment length polymorphism (RFLP) in intron 18 and of the multiallelic dinucleotide repeats in introns 13 and 22, followed by analysis of other intragenic polymorphisms. This procedure yielded an informativity rate of almost 100%. Of the 96 females examined by linkage polymorphism analysis, 78 belonged to 25 families with more than one haemophiliac and 29 of them were obligate carriers. In 47 of the 49 suspected carriers linkage polymorphism analysis enabled definition of carriership based on intragenic polymorphisms. 18 of the 96 females belonged to eight families with sporadic haemophilia cases and only eight of the 18 suspected carriers could be diagnosed by exclusion.In nine pregnant women carrying factor VIII gene inversions, mRNA extracted from chorionic villus samples (CVS) was analysed for factor VIII gene inversion by reverse transcription/polymerase chain reaction (RT/PCR). This procedure enabled rapid prenatal diagnoses in six male fetuses. Taken together, our data indicate that a high rate of informativity and carrier definition is possible by the strategy of first screening for factor VIII gene inversions, and, if none are found, sequential use of highly informative intragenic polymorphisms, followed by less informative intragenic and extragenic polymorp

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00003.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.Haemophilia A is an X‐linked recessive bleeding disorder of variable severity that is caused by a deficiency of coagulation factor VIII (FVIII). The disease results from mutations in the FVIII gene which are heterogenous both in type and position within the gene. Recently, however, inversion mutations were found to be common to patients with severe disease (Lakichet al., 1993). These mutations result from intrachromosomal recombinations between DNA sequences in the A gene (located in intron 22 of the FVIII gene) and one of two A genes upstream to the FVIII gene. To determine the frequency of these inversions we performed Southern blot analysis on banked DNA from 166 consecutive, unrelated haemophilia A families previously referred for carrier or prenatal testing. In 57/166 (34%) families an inversion or other unique mutation was detected. The distal and proximal A genes lying upstream to the FVIII gene were involved in 79% and 18% of the mutations, respectively, but in 3% of the families the sequences involved in the mutation have not been identified. In 20/38 (53%) families with severe disease a mutation was detected. Interestingly, the relative risk of developing inhibitors in patients with FVIII gene inversions or other 3° mutations detected by this assay, as compared to patients with no detectable mutation by this assay, was 3.8. In families for which a mutation is detected, direct DNA testing is an accurate and inexpensive alternative to linkage analysis for prenatal or haemophilia A carrier testi

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00004.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.Haemophilia B (Christmas disease) is an X‐linked bleeding disorder resulting from an inherited deficiency of coagulation factor IX activity. Due to the heterogeneity of mutations within the factor IX gene there is a marked clinical variability in disease severity. By applying techniques of mutational analysis and direct sequencing of PCR products it is now potentially possible to determine the pathogenic gene defect in entire haemophilia B populations. We report here characterization of the factor IX gene defect in all the haemophilia B patients in New Zealand as part of a nationwide approach towards providing efficient and cost‐effective haemophilia B genetic counselling services for these families. Twenty‐six different mutations were identified in 32 unrelated haemophilia B families. Three defects at nucleotide positions +8,6659 and 17696 are novel mutations which have not been reported by other laboratories. A PCR‐based diagnostic screening test for direct mutational analysis could be performed in most cases; 17 of the 26 mutations altered a restriction enzyme recognition sequence and, with the exception of the total gene deletion, base changes not affecting a restriction enzyme site could be detected by allele‐spe

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00005.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.This survey provides new information on the severity of factor IX deficiencies among patients being treated for haemophilia B and on the prevalence of factor IX inhibitors in this population. A questionnaire was sent to 150 haemophilia treatment centres in the United States and Canada. 82 centres responded and provided data on 1967 patients with haemophilia B. 37% of these patients had severe haemophilia B (10 BU in 17 patients. Factor IX inhibitors are much less common in patients with haemophilia B than in patients with haemop

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00006.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.The identification of infrequent side‐effects of clotting factor concentrates, undetected by clinical trials, is facilitated by post‐marketing surveillance. We present a post‐marketing surveillance study in which 97 patients with haemophilia A, attending three haemophilia centres, were treated over a median follow‐up period of 284 days (range 1–1074), and a total follow‐up period of 30,080 days, with a pasteurized immunoaffinity purified factor VIII concentrate (Monoclate‐P, Armour, Collegeville, USA). 5216 infusions, using 10,527,000 units of Monoclate‐P, were carried out, mostly for routine haemarthroses or prophylaxis.No new inhibitors were observed during the study. At the start of the study 60/97 were HIV seropositive, 67/97 HBs antibody positive, 12 HbsAb negative and the remainder HBsAb positive before the study period. 13/14 tested were HAV seropositive at the beginning of the study. One patient became HAV seropositive during the study period, an infection thought to be community acquired. No other seroconversions were observed. Only one mild transfusion reaction was observed. This study confirms the safety and efficacy of Monoclate‐P. Post‐marketing surveillance or nationally organized pharmaco‐vigilance should be practiced more widely to enable identification of low‐frequency si

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00007.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.As a consequence of recent outbreaks of HAV infection by blood products, 91 patients, haemophiliacs and subjects with bleeding disorders (10 of whom were also anti‐HIV positive) susceptible to HAV infection received a formalin‐inactivated hepatitis A vaccine (HAVRIX 720 Elisa Units, SmithKline Beecham). Subcutaneous injections were given in the deltoid region at 0, 1 and 6 months. The seroconversion rates and litres, expressed in GMT IU/1, were determined at 1, 2, 6, 7, 12, 18 and 24 months. No adverse reactions to the vaccine were observed. The highest percentage of responders observed was 98.7% in anti‐HIV negative and 71.4% in anti‐HIV positive patients. The anti‐HAV GMT titres were higher in anti‐HIV negative than in anti‐HIV positive patients. The inactivated hepatitis A vaccine is safe, clinically well tolerated, and provides long‐term protection agains

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00008.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.A World Federation of Hemophilia External Quality Assessment Scheme has been established to promote high standards of laboratory performance in haemophilia centres worldwide. Twenty‐two International Haemophilia Training Centres (IHTCs) participated in a pilot study designed to assess between‐laboratory agreement and to establish target values for the prothrombin time, activated partial thromboplastin time, factor VIII:C, IX:C and von Willebrand factor assays. Although variations in results and clinical interpretations were observed between the centres, median results and assay precision were comparable to that seen in the United Kingdom National External Quality Assessment Scheme. IHTC‐generated median results were therefore considered appropriate target values against which to compare the performance of haemophilia centres in developing coun

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00009.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.Knee haemarthroses are very common in the haemophiliac and often, despite infusion of the missing coagulation factor, synovitis develops. The warm swollen joint is maintained in the most comfortable position for the haemophiliac: flexion. Ambulation is achieved by planterflexion of the ankle joint and toewalking. As the chronic synovitis persists, the range of movement of the knee is affected, with loss of full extension. Development of radiological degenerative signs develop. The quadriceps muscle usually weaken due to disuse, but the hamstrings are active in maintaining the flexion of the joint. As the process continues, the tibia subluxes posteriorly on the condyles of the femur. The posterior capsule of the knee joint soon contracts, permanently limiting knee extension. A case is described on whom an Ilizarov device was used to gradually return the limb to a function position. This will allow the patient to complete his growth prior to a definitive orthopaedic procedure.

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00010.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY