Factor VIII inhibitor. Gruppo Italiano Coagulopatie Congenite.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
A Ghirardini
Publications and source records attributed to A Ghirardini.
Testing practices and spread of HIV among sexual partners of HIV-positive haemophiliacs in Italy. Gruppo Italiano Coagulopatie Congenite.
OBJECTIVES: To evaluate rates and predictors of testing and HIV positivity among the sexual partners of Italian HIV-positive haemophiliacs. METHODS: Our index cases were 602 sexually active HIV-positive haemophiliacs (aged 18 years or more) enrolled in the Italian Registry of Haemophilia. Data on the demographic and clinical status of the haemophiliacs, whether their partners had undergone HIV testing, and the results of these tests were collected. RESULTS: To date, 205 (34.1%) partners of HIV-positive haemophiliacs have been tested for HIV, of whom 27 (13.2%) were seropositive. On univariate analysis, haemophiliacs who were unmarried, younger, and asymptomatic were less likely to have partners who had been tested for HIV (P << 0.001). On multivariate analysis, unmarried status [odds ratio (OR), 8.4; 95% confidence interval (CI), 5.4-13.1; P << 0.001] and younger age (OR, 1.9; 95% CI, 1.1-3.2) again predicted a higher rate of non-tested partners. There was no association between the demographic and medical characteristics of HIV-seropositive haemophiliacs and the risk of HIV positivity among their sexual partners. CONCLUSION: This study demonstrates that a high proportion of sexual partners of HIV-positive haemophiliacs have not yet been tested for HIV. The single most important predictor of not being tested was the marital status of the index case. These results emphasize the need to strengthen prevention programmes aimed at minimizing the risk of heterosexual HIV transmission, particularly among younger unmarried haemophiliacs.
AIDS Serodiagnosis↗
Low risk of transmission of the human immunodeficiency virus by a solvent-detergent-treated commercial factor VIII concentrate.
A study evaluating the risk of a commercial factor VIII (FVIII) concentrate's transmitting the human immunodeficiency virus (HIV) was carried out on hemophiliacs, by using multiple serological markers and the polymerase chain reaction (PCR). Twenty-nine hemophiliacs, negative for HIV antibodies, were treated for 18 months with a concentrate that had been inactivated by solvent-detergent. HIV-1 antibodies and antigen were assayed during the follow-up period. At the end of the study, all patients were also tested by the HIV 1 + 2 combined antibody assay; Western blot (WB) antibody analysis; and in eight cases, by an HIV-1 PCR technique. Patients received a yearly median FVIII dose of 35,330 IU (range 3,300-306,000); the median number of lots given to each patient was 6 (1-45). During the follow-up period and at the end of the study, HIV-1 antibodies and antigen were not detected in any of the subjects. The HIV 1 + 2 combined assay and WB analysis carried out only at the end of the study were negative. HIV-1 PCR was negative in all the tested patients. This study has shown that this solvent-detergent-treated FVIII concentrate did not transmit HIV.
Detergents↗
Effects of different parametric estimates of seroconversion time on analysis of progression to AIDS among Italian HIV-positive haemophiliacs.
The purpose of this study was to estimate seroconversion time using different parametric methods and to assess their influence on the estimation of the incubation time between HIV infection and onset of AIDS. Study subjects were 712 HIV-positive haemophiliacs enrolled in the Italian National Registry of patients with congenital coagulation disorders. Seroconversion time was estimated using the mid-point of each seroconversion interval (MID), the median of each interval under an estimated uniform distribution with cutpoints at December 1981 and December 1985 (MUU), the median of each interval under an estimated Weibull distribution (MUW), and the median of three random values drawn from each interval under the Weibull distribution (RUW). Kaplan-Meier survival analysis showed that the cumulative incidence of AIDS over a 7-year period was 11.6 per cent (SE 1.3 per cent) when using the MID estimate of seroconversion time, 10.8 per cent (1.2 per cent) with the MUU estimate, and 13.4 per cent (1.3 per cent) and 12.3 per cent (1.3 per cent) when using MUW and RUW estimates, respectively. This study demonstrates that the estimate of seroconversion time does not seem to be a major factor affecting estimates of AIDS incidence since the different techniques for estimating HIV seroconversion time yielded very similar results.
Acquired Immunodeficiency Syndrome↗
Progression to AIDS among Italian HIV-seropositive haemophiliacs. Italian Group.
To investigate the interval between HIV-1 infection and the development of clinical AIDS among Italian patients with congenital coagulation disorders, a national cohort study was undertaken in 1988. Information was collected both retrospectively and prospectively on 499 HIV-1-positive patients enrolled in an ongoing national registry of patients with congenital coagulation disorders. Two methods were used to estimate each patient's seroconversion date: the mid-point between the last negative (either known or estimated) and the first positive test, and the median under a Weibull distribution, which was assumed to fit seroconversion data. The two methods of estimating the seroconversion time yielded similar results. The actuarial incidence of AIDS was estimated using the Kaplan-Meier survival analysis at 12.8% (95% confidence interval = 9.7-15.9) over 7 years for Italian haemophiliacs. Progression appears to be slow in the first 5 years after the infection, and to rise steadily thereafter. A strong association between faster progression and older age at seroconversion was found. Zidovudine-treated individuals seem to have a slower progression than untreated individuals, after controlling for CD4, but there was no association between progression and type and severity of the congenital disorder.
Acquired Immunodeficiency Syndrome↗
Induction of immunotolerance in hemophilia for high titre inhibitor eradication: a long-term follow-up.
Three hemophiliacs with high titre inhibitor were treated with a medium-high FVIII dose schedule (100 IU/kg bw daily) with the aim of inducing the immunotolerance. These patients were followed-up extensively concerning their immunological status and HIV serology. In all of them the inhibitor disappeared and normal FVIII kinetics were obtained after 22, 15 and 29 months. After eradication of the inhibitor, no recurrence took place in any of the patients. All the patients were HIV Ab positive before the beginning of the treatment. In one of them CD4+ cells fell progressively 32 months after the treatment was started, a full-blown AIDS showed up, and the patient died 5 1/2 years after the beginning of the treatment. In the second and third patient the CD4+ cells varied widely but remained greater than 400/microliter during the whole immunotolerance treatment. The latter two patients are AIDS and ARC free so far, but patient No. 2 developed a mild-to-severe thrombocytopenia. Considering the high cost of the treatment and the possibility that such an intensive administration of FVIII concentrates might worsen the immunological status of patients, this therapeutic procedure should only be applied with caution.
Adult↗
HIV antigen and virus-safety studies.
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Acquired Immunodeficiency Syndrome↗
Clinical evaluation of subcutaneously administered DDAVP.
1-deamino-8D-arginine vasopressin was given subcutaneously at the dosage of 0.3 micrograms/Kg. b.w. to 24 mild factor VIII deficient patients (16 mild, 2 moderate hemophiliacs and 6 patients with von Willebrand's Disease), to treat bleedings (10 episodes) or to prevent bleeding during and after dental extractions (6 extractions) and surgery (11 interventions). None of the patients who underwent surgery bled. The vasopressin analogue was effective in the early treatment of muscle hematomas and promptly stopped all mucosal hemorrhages. Most of the patients treated for "spontaneous" bleedings performed self-injections at home. The drug was administered in two pharmaceutical forms (4 and 40 micrograms/ml): no differences in the clinical outcome were found. No significant side effects were recorded. The subcutaneous route of DDAVP administration thus seems to be particularly useful (mainly in the concentrated pharmaceutical form) in treating mild factor VIII deficiencies even on self- and home-treatment basis.
Deamino Arginine Vasopressin↗
Concentrated DDAVP: further improvement in the management of mild factor VIII deficiencies.
This study was carried out to evaluate the pharmacological efficacy of a new concentrated 1 Deamino - (8-D-arginine)-vasopressin (DDAVP) preparation. Concentrated DDAVP (C-DDAVP), (40 micrograms/mL) was given subcutaneously (s.c.) in hemophilia and von Willebrand Disease (vWD), and the response was evaluated in terms of factor VIII/vWF (VIII/von Willebrand Factor) complex response. This response was also compared to that obtained using the currently available commercial preparation (4 micrograms/mL) given either s.c. or intravenously (i.v.). The maximal f. VIII response after s.c. C-DDAVP was reached one hour after the injection (means:3.5 times the resting values) with an average decline of 15% at two hours. The response to s.c. C-DDAVP in patients with hemophilia was slightly better than that obtained with the diluted brand, but the difference did not reach any statistical significance even when the schedules were compared in the same patients. In type I (platelet normal subtype) vWD, a higher response in terms of factor VIII:C increase in comparison with hemophiliacs was obtained. Both Ristocetin co-factor activity (RiCof) and bleeding time responded to this vasopressin analogue, when administered subcutaneously.
Deamino Arginine Vasopressin↗
Evaluation of the nature of mildly prolonged prothrombin times.
Twenty-one asymptomatic individuals with a mildly prolonged prothrombin time (greater than 2 SD from the prothrombin time of the reference plasma) were found to have a mild isolated factor VII (F VII) defect (mean 38.8 U/dl; SD 13.2). Factor VII antigen levels were also found to be reduced (mean 45.5 U/dl; SD 7.8) in 13 of them. These figures were compared with those of 50 normals and 28 obligatory heterozygotes for F VII deficiency. The phenotypical behaviors in the propositi were found to be equal to those of the F VII congenital deficiency heterozygotes: the discrepant one (VII+) and the nondiscrepant one (VII-/R). Fifteen families of the propositi could also be studied, totalling 55 additional individuals; in 25 of them (ten pedigrees) a mild F VII deficiency was found showing the same phenotypical features of the corresponding propositi. We therefore believe that these individuals with mild F VII deficiency can be considered as heterozygotes for the defect, since the other vitamin K-dependent clotting factors were normal; the defect is transmitted throughout the kindred with the same mode of inheritance as F VII congenital deficiency; and F VII:C and F VII:Ag levels are highly comparable with those of known obligatory heterozygotes for F VII deficiency. On the grounds of a careful statistical analysis we propose a formula which allows a discrimination between the two phenotypes of the heterozygotes for F VII congenital deficiency. In addition it is suggested that sensitive tissue thromboplastins should be used to pick up these mild defects.
Adolescent↗
Evaluation of factor VII antigen in factor VII congenital deficiencies with a new ELISA assay.
An evaluation of a new Enzyme Linked Immunosorbent Assay (ELISA) factor VII:Ag assay in factor VII congenital deficiencies was carried out. This assay was compared to factor VII:C assay and the Inhibitor Neutralization Assay (INA) for factor VII:Ag, both in normals and F VII-deficient patients. The correlations between ELISA F VII:Ag and VII:C, as well as the one between INA F VII:Ag and VII:C, were good (r = .86 and .81, respectively). The correlation between the two immunologic methods of assay in normals was fairly good (r = 0.73, P less than 0.001); whereas in mild F VII deficiencies (heterozygotes for F VII deficiencies), the two methods correlated very well (r = .96). In the severe deficiencies, ELISA F VII:Ag assay allowed the evaluation of F VII protein levels below 1 u/dl. The sensitivities of the INA and ELISA assays were evaluated by creating artificially prepared plasmas containing serial amounts of purified F VII: INA was unable to pick up F VII protein levels lower than 75 ng/ml, whereas the ELISA assay could detect up to 5 ng of F VII.
Adult↗
Danazol therapy in refractory chronic immune thrombocytopenic purpura.
We report our experience with danazol in the treatment of patients with refractory immune thrombocytopenic purpura (ITP). The effects of this drug were investigated in 10 patients, 6 males and 4 females, aged from 40 to 85 years, (median 58 years), with a platelet count below 50 X 10(9)/l. The patients had previously been treated with steroids; one of them had also been unsuccessfully splenectomized. Danazol was administered at a dosage of 600 mg/day for 3 months. Before and after treatment, detection of antiplatelet antibodies was performed. Seven patients were treated for 3 months. One of them showed a transient increase of platelet count, in the others, no significant rise was noted. Six patients experienced side effects during treatment. We think that danazol does not appear to be an alternative therapeutical approach in refractory ITP.
Adult↗
Heated clotting factors and seroconversion for human immunodeficiency virus in three hemophilic patients.
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Adolescent↗
Inhibitor to factor VIII in a non-haemophilic patient: evaluation of the response to DDAVP and the in vitro kinetics of factor VIII. A case report.
We report a case of inhibitor to factor VIII in a non-haemophilic patient. Immunosuppressive therapy with azathioprine was started, but without any advantage. Evaluation of the kinetics of exogenous factor VIII in vitro showed a rapid but incomplete neutralization of factor VIII. Following s.c. 1-deamino-8-D-arginine vasopressin (DDAVP) administration, a large and prolonged increase in factor VIII:C and von Willebrand factor antigen occurred together with complete inhibitor saturation. Therefore DDAVP may represent an important tool in the management of the bleeding episodes in these patients and evaluation of its suitability in the management of these patients should be carried out.
Blood Coagulation Disorders↗
Spectrum of HIV infection and AIDS in a cohort of Italian hemophiliacs.
A group of 173 subjects affected by congenital clotting factor deficiencies was evaluated with regard to the impact of HIV infection. On the whole, 78 patients (45%) were found to be HIV Ab-positive. As of March, 1988, of the seropositive patients, 63 (80.8%) had an asymptomatic HIV infection (Group II/CDC), three (3.8%) had a persistent generalized lymphadenopathy (Group III/CDC). The 12 (15.4%) remaining patients could be classified in Group IV of the CDC classification due to their symptoms and signs; in particular, 10 came under surveillance case definition for AIDS. Assay for the HIV antigen was positive in 14 (17.9%) seropositive hemophiliacs. With regard to the immunological features, our data clearly show that a sharp decline in the number of CD4+ cells was associated with symptomatic forms of the disease. An evaluation of the time elapsed from seroconversion to the appearance of the symptomatic clinical condition showed an average incubation of 37 months.
Acquired Immunodeficiency Syndrome↗
[Open psychiatric deparments in general hospitals. Statistical report on the functioning of the psychiatric department of the Nervous and Mental Disease Clinic in the Hospital Institutes of Modena].
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Adolescent↗
The impact of antiviral therapy with zidovudine: a retrospective study on HIV-positive hemophiliacs in Italy. Italian Group of Congenital Coagulopathies.
BACKGROUND: The effects of zidovudine (ZDV) treatment on progression to AIDS are not completely clear. This study evaluated the effects of ZDV treatment on the progression to AIDS in HIV-positive hemophiliacs. METHODS: A retrospective study was carried out on HIV-infected hemophiliacs: it included 238 individuals, 119 each from the treated and the non-treated groups. For the group receiving ZDV, we included those for whom a CD4+ count was available prior (median = 1 month) to beginning therapy. The cumulative incidence of developing AIDS was estimated by the Kaplan-Meier method. To identify factors independently associated with progression to AIDS, a Cox proportional hazards model was used. RESULTS: The cumulative incidence of developing AIDS at 8 years after HIV seroconversion was 10.4% [standard error (SE) = 2.8%] for the treated group and 17.1% (SE = 3.8%) for the non-treated group. The difference was statistically significant (p = 0.01). By multivariate analysis, ZDV therapy and CD4+ T-cell count > 200/mm3 were the parameters independently associated with a slower progression to AIDS. CONCLUSIONS: Treatment with zidovudine seems to slow the progression to AIDS in HIV-positive hemophiliacs.
Acquired Immunodeficiency Syndrome↗