摘要:

Summary.In HIV‐seronegative haemophiliac patients abnormal immune parameters have been demonstrated. In this review data on these abnormalities, their aetiology and clinical consequences are summarized and discussed. The data reviewed show abnormalities at different levels of the adaptive immune system. Most of the reported abnormalities regard lymphocyte subsets and their function, bothin vivoandin vitrotesting. Strong evidence has not been found for a causal relation between abnormalities and the consumption of factor VIII concentrates nor the purity of the concentrates. It seems likely that certain contaminants in the factor VIII concentrates have an inhibiting effect on lymphocytes and monocytes. Two clinical consequences of the abnormalities have been suggested: a higher susceptibility for infections and a greater risk to develop malignancies. Data on these consequences, however, are contradicting and not in agreement with the good results of long‐term treatment of HIV‐seronegative haemophiliac patients with factor VIII concentrates. The studies reviewed give no convincing evidence that more pure concentrates are advantageous in HIV‐negative haemop

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00017.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.Type II B von Willebrand disease (vWD) is a rare subtype of vWD characterized by the presence of an abnormal von Willebrand factor (vWF) with enhanced affinity for the platelet membrane receptor glycoprotein Ib. The phenotypic hallmarks of the disease are represented by heightened ristocetin‐induced platelet aggregation, occurring at very low ristocetin concentration, and the lack of high‐molecular‐weight vWF multimers in plasma. When infused with desmopressin, a variable degree of thrombocytopenia usually occurs in these patients, resulting fromin vivoplatelet aggregation caused by the release of abnormal vWF multimers from endogenous stores. We have reviewed the available literature data concerning the biological and clinical effects of desmopressin in the few cases so far reported. Despite the fear of thrombotic or haemorrhagic events, no significant side‐effects have been reported also in the cases (70%) with severe thrombocytopenia. Moreover, the few clinical reports with the use of desmopressin in type II B patients showed a favourable effect in the prevention of bleeding during surgery or dental extraction. Thus, it appears that desmopressin could be safely used in selected clinical situations in patients with type I

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00018.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.On the basis of evidence from the immune systems of patients with haemophilia infected with HIV, patients in the UK have been switched to high‐purity clotting factor concentrates. However, there is very little information currently available on the effect of intermediate‐purity clotting factor concentrates on progression of HIV disease. Among 99 HIV‐positive men with severe factor VIII deficiency registered at The Royal Free Hospital Haemophilia Centre, a 100 IU kg‐1increase in the yearly amount of concentrate received did not appear to be associated with more rapid progression to AIDS, death or to a low CD4 count. However, the use of total concentrate usage may mask a more subtle effect of specific concentrate contaminants on the progression of HIV

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00019.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.Randomized and cohort studies have provided evidence confirming the hypothesis, based onin‐vitroobservations, that the use of very high‐purity factor VIII (FVIII) concentrates, either immuoaffinity chromatography purified or produced by recombinant DNA technology, may slow immunological deterioration in human immunodeficiency virus (HIV)‐infected haemophiliacs, while high‐purity concentrates, produced by ion‐exchange chromatography, did not produce a benefit. Even though these data clearly indicate that very high‐purity concentrates should be preferred for the replacement therapy of HIV‐positive haemophiliacs, there are little data, based on direct comparison, supporting the use of very high‐purity concentrates rather than high‐purity preparations, which are less expensive. In an attempt to address this issue, we prospectively compared CD4 cell counts and changes of clinical status in 18 HIV‐positive haemophiliacs, randomly assigned either to receive the treatment with a very high‐purity FVIII concentrate, purified by immunoaffinity chromatography, or a high‐purity product, produced by ion‐exchange chromatography. All patients had CD4 lymphocyte counts below 300 μL‐1, were negative for the hepatitis B surface antigen and the HIV p24 antigen, and were receiving antiretroviral treatment with Zidovudine for at least 6 months. There were no significant changes of CD4 cell counts over the 96‐week follow‐up period or between the two groups. No signficant differences between the two groups were detected in the occurrence of AIDS‐defining diagnoses (one in each group). On the whole, no striking benefit is conferred to the immune status of asymptomatic HIV‐positive haemophiliacs by using either of these high‐purity and very high‐purity FVIII concentrates for 96 weeks. Larger prospective randomized trials are needed to establish definitely whether it is necessary to resort to very high‐purity concentrates or it is sufficient to use high‐purity concentrates to slow the fall of CD4 cell counts that occurs in HIV‐positive haemophiliacs. Randomized trials, based on clinical end‐points, are also needed to demonstrate whether slowing the fall in CD4 cells results in cl

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00020.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.Using a binding assay to immobilized factor VIII (F VIII) (ELISA) we measured the amount of IgG with binding capacity to FVIII, in the plasma of patients with an inhibitor to F VIII, in multitransfused haemophiliacs without inhibitor and in a control group of blood donors. It was shown that the amount of IgG bound to VIII was elevated in patients with an inhibitor although a weak correlation could be established between the inhibitor titre (BU) and the amount of bound IgG. In all haemophiliacs without inhibitor, IgG bound to F VIII were present. Although the mean value of IgG bound to F VIII was significantly lower than the amount detected in patients with F VIII inhibitors, a group of patients developed an equal amount of IgG recognizing the F VIII molecules to the amount of IgG measured in inhibitor patients. These results indicate that the presence of an inhibitor is not related to the amount of specific IgG bound to F VIII but more likely to the position of epitopes recognized by specific IgG. The presence of IgG bound to F VIII was detected in 92% of control blood donors and an inhibitor to F VIII ranging from 0.5 to 1.3 BU mL‐1in 17% of them. The isotypes of bound immunoglobins were identified in patients and controls: IgG4 subclass was predominant only in patients with an inhibitor and usually associated with antibodies of one or more of the other subclasses. In noninhibitor patients, very few had antibodies of IgG4 subclass with binding capacity to F VIII. These results raised the question of the clinical significance of these antibodies in multitransfused patients. The study indicates that binding assay is a complementary test to be used in multitransfused patients but cannot be used instead of the coagulation tests for detection of inhibitor

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00021.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.During treatment of a haemophilia A patient with a high‐responding inhibitor against factor VIII coagulant activity (VIII:C), we observed a difference in recovery of VIII:C depending upon which factor concentrate was infused. Inhibitor plasma samples or IgG fraction from seven patients were tested against a panel of seven different commercially available factor VIII concentrates of which five were plasma‐derived and two recombinant. In two of the plasma samples, inhibitor titres manifested a wide range of values depending upon which concentrate was used in the test system. Thus, inhibitor neutralization was less and VIII:C recovery greater when factor VIII concentrates containing large amounts of von Willebrand factor were used than when highly purified concentrates containing no von Willebrand factor or only trace amounts were used. In both of these two patients the inhibitor was directed against the light chain of factor VIII, and it is possible that the epitope of the light chain with which the inhibitor reacts is partly blocked by the von Willebrand factor.We conclude that inhibitors may differ in their reactivity with factor VIII molecules contained in clotting factor concentrates, and that there is factor VIII epitope variation between different concentrates. These findings have implications for the selection of concentrates for the treatment of inhibitor patients and the haemostatic effect may be improved if a concentrate giving the lowest inhibitor titre is chosen. Thus,in vitrotesting of inhibitor reactivity with a panel of concentrates is recommended when treatment of inhibitor patients with factor VIII concentrates is conside

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00022.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.With the advent of new viral inactivation and purification methods for factor concentrates in the 1980s, transmission of both HIV‐1 and hepatitis viruses has been significantly decreased. However, on routine annual testing of the paediatric population at the New England Hemophilia Center (NEHC), several children were noted to be hepatitis C (HCV) seropositive. Thus, a retrospective review of children with severe haemophilia was undertaken. Twenty‐six children (median age: 7.5 years) under the age of 12 were identified. All were HIV‐1 seronegative and had received hepatitis B immunization. Of these, 22 had received factor concentrate. Four children had no documented HCV serostatus, and seven were HCV seropositive using a second‐generation ELISA. Transfusion products were reviewed and stored serum samples were evaluated using a second‐generation ELISA to identify the approximate date of seroconversion with positive tests confirmed by RIBA analysis. Three children became seropositive before 1989 using factor concentrates with early viral attenuation procedures. Two children who seroconverted after 1991 received only monoclonal affinity purified factor concentrate that was either pasteurized or solvent/detergent treated. There was no evidence of horizontal or nosocomial viral transmission. We are unable to prove causality with the factor concentrates used by these children. Continued surveillance with sensitive measures for detection of HCV in persons with haemophilia using plasma‐derived factor concentrate i

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00023.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.Beta interferon therapy was given to seven chronic hepatitis C patients with haemophilia or other haemorrhagic disorders who had received clotting factor replacement therapy. Serum alanine aminotransferase (ALT) levels ranged from 82 to 275 UL‐1and hepatitis C virus (HCV)‐RNA ranged from 106to 109copies mL‐1. HCV‐genotypes were I+II in one patient, II in one, II+III in four and IV in one. Patients received 6 mega units (MU) daily of natural type beta interferon by intravenous infusion for 6 weeks. In three of seven patients, the protocol was modified to intermittent administration because neutrocytopenia (under 500 × 106L‐1) developed in two patients and thrombocytopenia (under 50 × 109L‐1) was observed in one during treatment. No modification was necessary with regard to daily and total dose. All patients received administration without any haemorrhagic complications. Six of seven patients showed improvement in serum ALT levels, and one of the patients showed normalization of ALT levels for 6 months after treatment. HCV‐RNA disappeared in four patients by the end of treatment, although no one remained negative 6 months after treatment. The results of our study were similar to those reported in previous papers which described the use of alpha interferon in haemophiliacs. The reason none of the patients showed sustained loss of HCV‐RNA after therapy might be associated with high HCV‐RNA levels, characteristics of the HCV‐genotype and prolonged du

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00024.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.This paper describes the current status of counselling for HIV‐positive haemophiliacs at a haemophilia centre in Japan. Clinical experience with 23 HIV‐infected haemophiliacs (all male, age range 16–56, mean 29.9 years), 22 family members (eight couples of parents, one grandmother, five siblings) and nine sexual partners (five wives and four girlfriends) between April 1990 and February 1994 is detailed. Methods of counselling consisted of individual counselling in 32, couple counselling in eight and family counselling in three cases. Indications for counselling consisted of fear of or shame of HIV infection in 37, concern for the family in 21, risk of transmitting HIV to sexual partners in 12, fear of death and dying in 12, future career and family life in seven, interest in treatment options in five, daily life style in 10, parents' feeling of guilt over the infection in five cases, lack of knowledge of haemophilia, HIV infection and AIDS in seven, and bereavement in two cases. A total of 200 counselling hours were provided. Consequently, pending disclosure of HIV infection was successfully completed in five, disclosure of HIV infection to the sexual partner by the patient was facilitated in two, the patient‐family relationship improved in nine, and smooth transition of care to the adult in‐hospital unit was achieved in two patients. Our experience in Japan clearly verifies the importance of psychoeducational counselling for HIV‐positive haemophiliacs and their family as well as sexu

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00025.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.Prior to the availability of test for hepatitis ‘C’ in 1989, any elevated AST in a pooled blood product recipient was presumed to be from non‐A–non‐B hepatitis. We report a patient who received pooled factor VIII in 1984 and had persistently elevated AST which proved to be of nonhepat

ISSN:1351-8216    

DOI:10.1111/j.1365-2516.1996.tb00026.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY