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1.
Pediatr Hematol Oncol ; 11(1): 55-62, 1994.
Article in English | MEDLINE | ID: mdl-8155501

ABSTRACT

Detection of hemophilia carriers is an important issue and should be addressed with great care. The allelic frequencies of three intragenic probes (Bcl I for probe p114.12, Xba I for probe p482.6, and Bgl I for probe C) and one linked probe (Bgl II for probe DX 13) are reported, together with their diagnostic yield singly and in combination. In this series, 725 individuals (405 females) in 156 families were analyzed for restriction fragment-length polymorphisms. A total of 255 females (63%) were found to be informative for their carrier state with one or more probes. The most informative intragenic probe was p482.6 (useful in 49% of informative females). The most informative probe was DX 13 (useful in 59% of informative females), but this is a linked probe that carries a 5% risk of cross-over. By the use of probes p114.12, p482.6, and DX 13, almost 98% of all the informative females could be detected. In about 71% of families with a family history and a known carrier, prenatal diagnosis was feasible.


Subject(s)
Alleles , DNA/analysis , Gene Frequency , Genetic Carrier Screening , Hemophilia A/genetics , DNA Probes , Female , Genetic Linkage , Humans , Male , Prenatal Diagnosis/methods
2.
Br J Haematol ; 84(2): 269-72, 1993 Jun.
Article in English | MEDLINE | ID: mdl-8398829

ABSTRACT

Twenty-seven factor VIII deficient patients who had previously not been treated with blood or blood products were studied after infusion of a total of 24 batches of NHS factor VIII (8Y) concentrate produced by Bio-Products Laboratory, Elstree. Follow-up was carried out according to guidelines laid down by the International Society for Thrombosis and Haemostasis. Serial estimations of amino transferase level carried out over a 26-week period revealed no elevation of these enzymes attributable to hepatitis. Studies of various virological markers found no evidence of infection with hepatitis C, hepatitis B or HIV following transfusion. This confirms a previous finding that severe dry heating of factor VIII at 80 degrees C for 72 h seems to reduce the risk of transmitting hepatitis C from approximately 90% to a rate of 0-11%.


Subject(s)
Drug Contamination/prevention & control , Factor VIII/therapeutic use , Hot Temperature , Adult , Aged , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Child , Child, Preschool , Female , Hepatitis C/prevention & control , Hepatitis C/transmission , Humans , Infant , Male , Middle Aged , Time Factors
3.
Br J Haematol ; 83(2): 296-305, 1993 Feb.
Article in English | MEDLINE | ID: mdl-8457478

ABSTRACT

Concern has been expressed that intermediate purity clotting factor concentrates may cause immunological abnormalities in haemophilic patients, distinct from those related to HIV infection. Early reports of lymphocyte dysfunction in anti-HIV seronegative haemophiliacs pointed to activation of their lymphocytes; a potential cause of CD4+ ve lymphocyte decline in anti-HIV seropositive patients. Recent reports have suggested that the use of high purity FVIII concentrates might retard the rate of decline in CD4+ ve lymphocytes in haemophiliacs infected with the HIV virus. Expression of markers of acute and chronic activation of T and B lymphocytes was measured in heavily treated anti-HIV seronegative haemophiliacs using two-colour flow cytometry. No T or B lymphocyte stimulation was observed. Cellular markers of activation were absent and CD4+ ve lymphocyte counts and serum IgG levels were normal. Anti-HIV seropositive haemophiliacs showed T and B cell activation consistent with HIV infection. The extent of lymphocyte activation in individual patients was unrelated to the type, amount or frequency of FVIII received. These findings do not support the hypothesis that lymphocytes of haemophiliacs are affected directly by the regular administration of intermediate purity concentrates so as to accelerate the progression of HIV disease.


Subject(s)
Factor VIII/immunology , Lymphocyte Activation , Adolescent , Adult , Aged , B-Lymphocytes/immunology , CD4 Antigens/analysis , Child , HIV Seropositivity/immunology , Hemophilia A/therapy , Humans , Male , Middle Aged , T-Lymphocytes/immunology
4.
Clin Exp Immunol ; 88(2): 243-52, 1992 May.
Article in English | MEDLINE | ID: mdl-1349272

ABSTRACT

With the advent of standard flow cytometric methods using two-colour fluorescence on samples of whole blood, it is possible to establish the ranges of CD3, CD4 and CD8 T lymphocyte subsets in the routine laboratory, and also to assist the definition of HIV-1-related deviations from these normal values. In 676 HIV-1-seronegative individuals the lymphocyte subset percentages and absolute counts were determined. The samples taken mostly in the morning. The groups included heterosexual controls, people with various clotting disorders but without lymphocyte abnormalities as well as seronegative homosexual men as the appropriate controls for the HIV-1-infected groups. The stability of CD4% and CD8% values was demonstrated throughout life, and in children CD4 values less than 25% could be regarded as abnormal. The absolute counts of all T cell subsets decreased from birth until the age of 10 years. In adolescents and adults the absolute numbers (mean +/- s.d.) of lymphocytes, CD3, CD4 and CD8 cells were 1.90 +/- 0.55, 1.45 +/- 0.46, 0.83 +/- 0.29 and 0.56 +/- 0.23 x 10(9)/l, respectively. In patients with haemophilia A and B the mean values did not differ significantly. In homosexual men higher CD8 levels were seen compared with heterosexual men and 27% had an inverted CD4/CD8 ratio but mostly without CD4 lymphopenia (CD4 less than 0.4 x 10(9)/l). However, some healthy uninfected people were 'physiologically' lymphopenic without having inverted CD4/CD8 ratios. When the variations 'within persons' were studied longitudinally over a 5-year period, the absolute CD4 counts tended to be fixed at different levels. As a marked contrast, over 60% of asymptomatic HIV-1+ patients exhibited low CD4 counts less than 0.4 x 10(9)/l together with inverted CD4/CD8 ratios. Such combined changes among the heterosexual and HIV-1-seronegative homosexual groups were as rare as 1.4% and 3%, respectively. For this reason, when the lymphocyte tests show less than 0.4 x 10(9)/l CD4 count and a CD4/CD8 ratio of less than unity, the individuals need to be investigated further for chronicity of this disorder, the signs of viral infections such as HIV-1 and other causes of immunodeficiency.


Subject(s)
CD4-CD8 Ratio , HIV Infections/diagnosis , HIV-1 , T-Lymphocyte Subsets , Adolescent , Adult , Aged , Aging/immunology , CD4-Positive T-Lymphocytes , Child , Female , HIV Infections/immunology , Hemorrhagic Disorders/immunology , Homosexuality , Humans , Leukocyte Count , Male , Middle Aged , Reference Values
5.
Clin Exp Immunol ; 88(1): 6-9, 1992 Apr.
Article in English | MEDLINE | ID: mdl-1348668

ABSTRACT

After a maximum of 11 years (median 8.3 years) from the time of HIV seroconversion, 25 out of 59 (42%) of CMV-seropositive haemophiliacs had progressed to AIDS, as opposed to eight out of 50 (16%) CMV seronegatives. The age-adjusted relative risk for AIDS among CMV seropositives was 2.4 (P = 0.03). In order to determine how this adverse effect is mediated, the mean rate of decline in serial CD4+ lymphocyte counts was studied. CD4+ lymphocyte counts tended to decline more rapidly in CMV seropositives than in seronegatives (-0.087 x 10(9)/l per annum versus -0.082 x 10(9)/l per annum), but this difference did not reach statistical significance. The average CD4+ lymphocyte count at the time of HIV seroconversion was estimated to be similar in CMV seropositives and negatives, because in HIV-1-negative haemophiliacs the CD4+ counts were virtually identical, after adjustment for age (0.94 x 10(9)/l and 0.97 x 10(9)/l, respectively). The median CD4+ cell count at which AIDS developed was higher in the CMV-seropositive group (0.07 x 10(9)/l) than in the seronegative group (0.04 x 10(9)/l), but this difference did not reach statistical significance. We conclude from these findings that the adverse effect of CMV is not wholly mediated via a more rapid loss of CD4+ cells. We discuss other processes that may be mediated by CMV, such as a functional deficiency of residual CD4+ cells, or dissemination of HIV in other organs, which may be important in determining the earlier onset of AIDS among CMV-seropositive subjects.


Subject(s)
Acquired Immunodeficiency Syndrome/etiology , CD4-Positive T-Lymphocytes/immunology , Cytomegalovirus Infections/complications , HIV Infections/complications , Hemophilia A/complications , Acquired Immunodeficiency Syndrome/immunology , Cytomegalovirus Infections/immunology , HIV Infections/immunology , Humans , Leukocyte Count
6.
Thromb Haemost ; 67(3): 314-9, 1992 Mar 02.
Article in English | MEDLINE | ID: mdl-1641821

ABSTRACT

Factor XI deficiency is an uncommon bleeding disorder usually manifested by excessive bleeding after surgery or trauma. Until recently the only effective therapy has been fresh-frozen plasma (FFP) infusion. We describe the efficacy and safety of a new factor XI concentrate produced from human donor plasma by a modification of the method used for antithrombin III concentrate. The mean recovery of factor XI in the circulation measured on 62 occasions was approximately 91% of the injected dose, and the mean half-disappearance-time was 52 h. The concentrate was used for 31 invasive procedures in 30 patients, including 16 patients who had a definite bleeding tendency on previous occasions, with normal haemostasis being achieved in all but 1. Only 1 patient (previously experiencing allergy to FFP) experienced adverse effects during infusion. Monitoring of liver function tests and viral antibody status in suitable patients has shown no evidence of transmission of hepatitis viruses, HIV-1 or parvovirus B19. We conclude that this concentrate provides effective treatment for patients with factor XI deficiency. Preliminary results suggest safety from virus transmission, but this needs to be established in further studies of previously untreated patients.


Subject(s)
Factor XI/therapeutic use , Adolescent , Adult , Aged , Child , Child, Preschool , Factor XI/adverse effects , Factor XI/isolation & purification , Hepatitis, Viral, Human/transmission , Humans , Middle Aged
7.
Transfusion ; 32(2): 134-8, 1992 Feb.
Article in English | MEDLINE | ID: mdl-1311876

ABSTRACT

A multicenter prospective study was carried out to evaluate whether a vapor-heated factor VIII concentrate transmitted blood-borne viral infections over a surveillance period of 15 months. Thirty-five patients with hemophilia and von Willebrand disease who had never received any blood components were treated. Twenty-eight were analyzed and found not to have non-A, non-B hepatitis. Sera from 20 of these 28 patients were also tested for the antibody to the hepatitis C virus. None had sero-converted during the follow-up period. None of the patients analyzed developed markers of the hepatitis B virus (n = 17) or the human immunodeficiency virus (n = 31). This vapor-heated factor VIII concentrate carries a low risk of transmitting hepatitis and human immunodeficiency virus infection.


Subject(s)
Factor VIII/therapeutic use , Hemophilia A/therapy , Virus Diseases/prevention & control , von Willebrand Diseases/therapy , Blood Transfusion , Child , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/etiology , Follow-Up Studies , HIV Infections/diagnosis , HIV Infections/etiology , Hepatitis B/diagnosis , Hepatitis B/etiology , Hepatitis C/diagnosis , Hepatitis C/etiology , Hot Temperature , Humans , Prospective Studies , Virus Diseases/diagnosis , Virus Diseases/etiology
9.
Clin Lab Haematol ; 14(2): 109-20, 1992.
Article in English | MEDLINE | ID: mdl-1633680

ABSTRACT

The techniques of Western blotting and the monoclonal antibody specific immobilization of platelet antigen (MAIPA) assay were used to detect antibodies to platelet glycoproteins in 43 samples of serum from 23 anti-HIV positive haemophiliacs (8 with severe thrombocytopenia, 6 with moderate thrombocytopenia, and 9 with a normal platelet count), six anti-HIV negative haemophiliacs and ten controls. Antibodies were present in the majority of anti-HIV positive patients' sera even before the onset of thrombocytopenia. Thrombocytopenia was associated with an increase in the incidence of antibodies to GPIIIa and GPIb, whereas the antigen most frequently recognized in patients without thrombocytopenia was GPIIb. Anti-GPIIb and/or GPIIIa reactivity was also seen in three out of the six anti-HIV negative patients. There was no correlation between the absolute platelet count and the detection of antibodies in either assay. Effective therapy for thrombocytopenia with zidovudine, interferon or splenectomy did not influence the presence of antibody. Eight of nine patients with AIDS were negative in the MAIPA assay, consistent with their depressed immune status. It is concluded that the production of antibodies to platelet membrane glycoprotein in anti-HIV positive haemophiliacs is influenced by factors other than HIV. The presence of such antibodies is independent of the platelet count and is therefore unlikely to play a causative role in HIV-related thrombocytopenia.


Subject(s)
HIV Antibodies/blood , HIV Infections/immunology , Hemophilia A/immunology , Platelet Membrane Glycoproteins/immunology , Thrombocytopenia/immunology , Transfusion Reaction , Antibodies, Monoclonal , Antibody Specificity/immunology , Blotting, Western , Enzyme-Linked Immunosorbent Assay , HIV Infections/blood , HIV Infections/etiology , Hemophilia A/blood , Hemophilia A/complications , Humans , Thrombocytopenia/blood , Thrombocytopenia/complications
10.
Article in English | MEDLINE | ID: mdl-1346274

ABSTRACT

A method is proposed for assessing the cumulative risk of various AIDS-defining conditions as the CD4 lymphocyte count declines in HIV-infected individuals. The method is analogous to survival analysis but is based on the CD4 lymphocyte count rather than on time. Thus, the level to which the CD4 lymphocyte count has declined, rather than the length of time since seroconversion, is considered as an individual's survival interval. The survival interval may be censored (due to lack of follow-up) or treated as an interval to failure (if the individual develops AIDS). The Kaplan-Meier (product-limit) estimates, of the proportion of individuals developing AIDS before reaching a given low CD4 lymphocyte count, may be useful for determining when prophylactic treatment should begin.


Subject(s)
Acquired Immunodeficiency Syndrome/immunology , CD4-Positive T-Lymphocytes/immunology , Leukocyte Count , Acquired Immunodeficiency Syndrome/blood , Acquired Immunodeficiency Syndrome/complications , Adolescent , Adult , Aged , Child , Child, Preschool , Cohort Studies , Follow-Up Studies , Hemophilia A/complications , Humans , Infant , Middle Aged , Risk Factors
11.
Am J Med ; 91(5A): 20S-22S, 1991 Nov 04.
Article in English | MEDLINE | ID: mdl-1746591

ABSTRACT

Highly purified porcine factor VIII:C (FVIII:C) concentrate prepared by polyelectrolyte fractionation has been available for therapeutic use since 1980. Over the last decade substantial international experience has confirmed the value of porcine FVIII:C in management of hemophilia with inhibitors, and recent studies have underlined its particular effectiveness in treating patients with the acquired form of the disease. The rationale for use of porcine FVIII:C is based on a twofold premise. First, most inhibitors interact less strongly with porcine FVIII:C than they do with the human factor; cross-reactivity is especially low, and often negligible, among patients with acquired disease. Second, when measurable levels of circulating FVIII:C can be achieved, the likelihood of clinical hemostasis is maximized. In a variable proportion of patients with the congenital disease, anamnestic rises in titers of the inhibitor against human FVIII:C may follow treatment with the porcine factor, and this phenomenon may constrain therapy. These events seem to occur rarely in persons with acquired inhibitors, however, thus broadening therapeutic application of porcine FVIII:C to these patients. Although anamnesis often is perceived as a limitation, significant untoward transfusion reactions are highly unusual after porcine FVIII:C therapy. Although early experience with this form of treatment centered on management of major bleeding episodes and hemostatic crises, use of porcine FVIII:C has more recently been extended to more routine bleeding problems, immune tolerance induction regimens, prophylaxis, and home therapy. These and other advances are discussed.


Subject(s)
Autoantibodies/analysis , Factor VIII/therapeutic use , Hemorrhage/therapy , Animals , Autoantibodies/immunology , Cross Reactions , Factor VIII/immunology , Hemophilia A/therapy , Hemorrhage/etiology , Hemorrhage/immunology , Humans , Swine
12.
AIDS ; 5(10): 1217-22, 1991 Oct.
Article in English | MEDLINE | ID: mdl-1686179

ABSTRACT

A cohort of 111 HIV-infected haemophiliacs has been followed for up to 11 years, during which time 33 patients have been diagnosed with AIDS. Twenty-seven of the cohort developed detectable p24 antigenaemia while remaining free of AIDS. These patients experienced an increased risk of progression to AIDS compared with those patients who were persistently p24-negative (relative risk 7.24; P less than 0.0001, Cox proportional hazards model). The relative risk was reduced to 5.42 (P less than 0.0001) after adjustment for age and cytomegalovirus seropositivity. After adjustment for the patients' declining CD4 lymphocyte count during follow-up, the relative risk fell dramatically to 1.97 and became non-significant (P = 0.2). p24-antigenaemic patients tended to develop AIDS at levels of similar CD4 lymphocyte counts to those who were persistently p24-antigen-negative (median CD4 lymphocyte counts, 70 and 50 x 10(6)/l, respectively). These results suggests that the association between p24 antigenaemia and the rate of progression to AIDS can be explained largely by a more rapid decline in CD4 lymphocyte count among patients with p24 antigenaemia than in those without. The major pathological effects of increased plasma viral load, as detected by the presence or absence of p24 antigenaemia, appear to act via progressive CD4 lymphocyte depletion.


Subject(s)
HIV Core Protein p24/blood , Acquired Immunodeficiency Syndrome/diagnosis , Acquired Immunodeficiency Syndrome/immunology , CD4-Positive T-Lymphocytes , Cohort Studies , HIV Seropositivity , Hemophilia A/complications , Humans , Lymphocyte Depletion , Predictive Value of Tests , Prognosis , Risk Factors
13.
Br J Haematol ; 78(3): 398-402, 1991 Jul.
Article in English | MEDLINE | ID: mdl-1651756

ABSTRACT

Stored sera from 28 patients with inherited coagulation disorders who had developed non-A non-B hepatitis (NANBH) following a first exposure to clotting factor concentrates and 15 similar, but unmatched, patients who had received blood products but had normal transaminases on sequential testing were tested using the Ortho enzyme-linked immunosorbent assay (ELISA) anti-HCV assay. Twenty-seven of the 28 patients with NANBH were anti-HCV positive after exposure. In 10 of those in whom dates of first exposure and seroconversion were well-defined, the median time interval to NANBH was 4 weeks (range 1-7) and to anti-HCV seroconversion was 11 weeks (range 7.5-14.5). None of the 15 patients without NANBH developed anti-HCV. This first generation Ortho ELISA anti-HCV assay showed 96% sensitivity and 100% specificity and has potential use as an adjunct in the surveillance of new clotting factor products.


Subject(s)
Hepacivirus/immunology , Hepatitis Antibodies/analysis , Hepatitis C/diagnosis , Adolescent , Adult , Aged , Blood Coagulation Factors/therapeutic use , Child , Child, Preschool , Enzyme-Linked Immunosorbent Assay , Hemophilia A/therapy , Hepatitis C/blood , Hepatitis C/etiology , Humans , Infant , Longitudinal Studies , Middle Aged , Transfusion Reaction
14.
Blood ; 77(9): 1942-8, 1991 May 01.
Article in English | MEDLINE | ID: mdl-2018835

ABSTRACT

Factor XI deficiency is a rare bleeding diathesis found predominantly in Ashkenazi Jewish kindreds. A recent study of six Jewish patients identified three distinct mutations (Types I, II, and III) in the factor XI gene that were sufficient to fully define the genotypes of the patients. We have investigated 63 patients with factor XI deficiency and find overall allele frequencies of 44% for the type II mutation, 31% for the type III mutation, and 0% for the type I mutation. Therefore, 25% of the mutant factor XI alleles in our sample remain undefined. However, the distribution of mutant alleles is significantly different between Jewish and non-Jewish populations with hitherto undefined mutations accounting for 84% of the disease alleles in non-Jewish patients. Plasma factor XI:C levels were found to differ significantly between different homozygous and compound heterozygous genotypes and the inheritance of the II/III genotype was found to carry an increased risk of the most severe bleeding tendency.


Subject(s)
Factor XI Deficiency/genetics , Alleles , Exons , Factor XI Deficiency/metabolism , Gene Frequency , Genotype , Hemorrhage/etiology , Humans , Jews , Mutation , Pedigree , Polymerase Chain Reaction , Restriction Mapping
15.
Aliment Pharmacol Ther ; 5(2): 199-205, 1991 Apr.
Article in English | MEDLINE | ID: mdl-1888820

ABSTRACT

Candidiasis of the oropharynx and oesophagus is one of the most common problems encountered in patients with HIV disease. Fluconazole is a bis-triazole antifungal agent with a long serum half-life. Sixteen anti-HIV positive patients (15 haemophiliacs and one blood transfusion recipient) with a clinical diagnosis of oropharyngeal candidiasis were treated with 50 mg fluconazole daily for 14-28 days and then either 150 mg fluconazole or placebo weekly for 6 months in a prophylactic phase. Clinical cure occurred in all patients, and mycological cure occurred in 13/16 (81%) patients. In the prophylactic phase, there were 2/5 (40%) relapses in the placebo arm compared with 1/8 (12.5%) in the fluconazole arm, but this was not statistically significant by Fisher's one-sided exact test (P = 0.31). It is concluded that fluconazole is an effective treatment of oropharyngeal candidiasis and has potential for prophylactic use.


Subject(s)
Candidiasis, Oral/drug therapy , Candidiasis/drug therapy , Fluconazole/therapeutic use , HIV Infections/complications , Hemophilia A/complications , Pharyngeal Diseases/drug therapy , Adolescent , Adult , Aged , Candidiasis/complications , Candidiasis/microbiology , Candidiasis, Oral/complications , Candidiasis, Oral/microbiology , Child , Double-Blind Method , Female , Fluconazole/adverse effects , Humans , Male , Middle Aged , Pharyngeal Diseases/complications , Pharyngeal Diseases/microbiology , Recurrence
16.
Lancet ; 337(8738): 389-92, 1991 Feb 16.
Article in English | MEDLINE | ID: mdl-1671424

ABSTRACT

Low CD4 lymphocyte counts are associated with increased risk of progression to AIDS in human immunodeficiency virus (HIV) infection. We investigated the extent to which the timing of progression to AIDS can be explained solely in terms of decline of the CD4 lymphocyte count in 111 haemophiliacs followed for up to 11 years since infection with HIV. A median of 10 CD4 lymphocyte counts were made per patient. By applying a simple linear model for the decline in CD4 lymphocyte counts over time, we estimated the date of development of AIDS in 96 patients who had at least 5 determinations. 84% (81 of 96) of patients were correctly classified as to development of AIDS before Jan 1, 1990 (p less than 0.0001), with this model. The results suggest that differences in the time at which patients with HIV will progress to AIDS can largely be explained by differences in rates of decline of CD4 lymphocyte counts.


Subject(s)
Acquired Immunodeficiency Syndrome/blood , CD4 Antigens/analysis , Hemophilia A/blood , Lymphocyte Subsets/pathology , Acquired Immunodeficiency Syndrome/immunology , Adolescent , Adult , Aged , Child , Child, Preschool , Follow-Up Studies , HIV Antibodies/analysis , Hemophilia A/immunology , Humans , Leukocyte Count , Lymphocyte Subsets/immunology , Middle Aged , Regression Analysis
17.
Article in English | MEDLINE | ID: mdl-1679845

ABSTRACT

The tendency for older people with HIV infection to progress more rapidly to AIDS than younger people was studied in a group of 111 anti-HIV-positive haemophiliacs followed for up to 10 years from seroconversion. After 7 years of seropositivity, those aged over 30 years at the time of the first positive anti-HIV test had a cumulative progression rate to AIDS of 50%, compared with only 12% for those aged 10-19 years (Kaplan-Meier estimates). Overall, the relative risk of developing AIDS by any given time after seroconversion was 1.45 for each 10 year increase in age (p = 0.002; 95% confidence limits of 1.15, 1.85; Cox proportional hazards model). After adjustment for the CD4+ T-cell count (median of 10 count measurements per patient, fitted as a time-dependent covariate), the relative risk fell to 1.31 but remained statistically significant (p less than 0.05; 95% confidence limits of 1.03, 1.67). This implies that older people may be at higher risk of progression than their younger counterparts, even if their CD4+ T-cell counts are the same. Hence, prophylaxis against opportunistic infections may be indicated at higher CD4+ T-cell counts in older people than in younger people.


Subject(s)
Acquired Immunodeficiency Syndrome/physiopathology , Aging , CD4-Positive T-Lymphocytes/pathology , HIV Infections/physiopathology , Leukocyte Count , Acquired Immunodeficiency Syndrome/blood , Acquired Immunodeficiency Syndrome/etiology , Adolescent , Adult , Aged , Child , Child, Preschool , Follow-Up Studies , HIV Infections/blood , HIV Infections/etiology , Hemophilia A/complications , Hemophilia A/drug therapy , Hemophilia A/physiopathology , Humans , Middle Aged , Proportional Hazards Models
19.
J Med Virol ; 33(1): 19-25, 1991 Jan.
Article in English | MEDLINE | ID: mdl-1826737

ABSTRACT

Haemophilic patients are at increased risk from hepatitis B virus infection because of their need for blood product therapy. They are potentially poor responders to hepatitis B vaccine due to immunological abnormalities resulting from two causes: infection with the human immunodeficiency virus and treatment with clotting factor concentrates. The protective antibody response to hepatitis B virus in vaccinated haemophiliacs was investigated using a competitive enzyme-linked immunosorbent assay which employs a monoclonal antibody, RF-HBs-1, that recognises a virus-neutralising epitope on HBsAg. Serum samples from 55 haemophilic patients were studied at 7, 12, and 24 months after the first injection with HB vaccine. Twenty-four vaccinated normal subjects were used as controls. The level of neutralising antibody was found to correlate with the polyclonal anti-HBs response in the majority of subjects in both the control and patient groups. There was a small but statistically significant reduction in both antibody responses in the patients compared with the normal controls. Treatment with FVIII or FIX concentrate did not influence the antibody response in the patients. Eleven of the haemophilic patients were anti-HIV seropositive. This group had a significantly lower antibody response than anti-HIV negative patients, and this correlated with the duration of anti-HIV seropositivity, rather than with their T4 counts. We conclude that, following vaccination, the majority of haemophiliacs are able to mount a protective antibody response to hepatitis B virus. HIV infection was found to be the sole cause of immunological suppression of this response.


Subject(s)
Hemophilia A/immunology , Hepatitis B Antibodies/biosynthesis , Hepatitis B virus/immunology , Hepatitis B/immunology , Adolescent , Adult , Aged , Binding, Competitive , Blood Coagulation Factors/therapeutic use , Child , Enzyme-Linked Immunosorbent Assay , Female , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/immunology , Hemophilia A/drug therapy , Hemophilia A/microbiology , Hepatitis B/complications , Hepatitis B/drug therapy , Hepatitis B Surface Antigens/immunology , Hepatitis B Vaccines , Humans , Infant , Male , Middle Aged , Neutralization Tests , Radiometry , Viral Hepatitis Vaccines
20.
Blood ; 76(5): 882-6, 1990 Sep 01.
Article in English | MEDLINE | ID: mdl-2118396

ABSTRACT

Home therapy with porcine factor VIIIC was safe and effective when administered to five hemophilic patients over periods of 8 1/2, 6, 4, 3 1/2, and 2 years. No significant transfusion reactions occurred. Before treatment with porcine factor VIIIC, all five had high-level, high-responding anti-human VIIIC inhibitors initially lacking anti-porcine factor VIIIC activity. Although specific anti-porcine VIIIC inhibitors arose in all patients, these were generally transient, and only one patient became refractory to treatment. We believe that porcine factor VIIIC is the treatment of choice in patients whose inhibitors do not cross-react. All five patients lost their original anti-human VIIIC inhibitors after starting treatment with porcine VIIIC, permitting the reintroduction of human VIIIC in three of them. There has been no recurrence of anti-human VIIIC inhibitor activity during 2 to 3 years of regular treatment with human VIIIC in these patients. This suggests that tolerance to human VIIIC has arisen as a result of treatment with porcine VIIIC. Porcine VIIIC may have a role in the desensitization of some factor VIIIC inhibitor patients.


Subject(s)
Factor VIII/therapeutic use , Hemophilia A/immunology , Immune Tolerance , Adolescent , Adult , Animals , Factor VIII/immunology , Follow-Up Studies , HIV Seropositivity , Hemophilia A/therapy , Humans , Male , Swine , T-Lymphocytes/immunology
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