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Biomedical subjects

M Morfini

Publications and source records attributed to M Morfini.

At least 55 records · Page 3Linked to original sources
PubMed1994

Clinical factors associated with progression to AIDS in the Italian cohort of HIV-positive hemophiliacs. G.I.C.C. Gruppo Italiano Coagulopatie Congenite.

This study updates estimates of the cumulative incidence of AIDS among Italian patients with congenital coagulation disorders (mostly hemophiliacs), and elucidates the role of age at seroconversion, type and amount of replacement therapy, and HBV co-infection in progression. Information was collected both retrospectively and prospectively on 767 HIV-1 positive patients enrolled in the on-going national registry of patients with congenital coagulation disorders. The seroconversion date was estimated as the median point of each patient's seroconversion interval, under a Weibull distribution applied to the overall interval. The independence of factors associated to faster progression was assessed by multivariate analysis. The cumulative incidence of AIDS was estimated using the Kaplan-Meier survival analysis at 17.0% (95% CI = 14.1-19.9%) over an 8-year period for Italian hemophiliacs. Patients with age greater than or equal to 35 years exhibited the highest cumulative incidence of AIDS over the same time period, 32.5% (95% CI = 22.2-42.8%). Factor IX recipients (i.e. severe B hemophiliacs) had higher cumulative incidence of AIDS (23.3% vs 14.2%, p = 0.01) than factor VIII recipients (i.e. severe A hemophiliacs), as did severe A hemophiliacs on less-than-20,000 IU/yearly of plasma-derived clotting factor concentrates, as opposed to A hemophiliacs using an average of more than 20,000 IU (18.8% vs 10.9%, p = 0.02). No statistically significant difference in progression was observed between HBsAg-positive vs HBsAg-negative hemophiliacs (10.5% vs 16.4%, p = 0.10). Virological, immunological or both reasons can account for such findings, and should be investigated from the laboratory standpoint.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Pharmacokinetics of monoclonally-purified and recombinant factor VIII in patients with severe von Willebrand disease.

A monoclonally-purified factor VIII (FVIII) concentrate, containing little von Willebrand factor (vWF), was infused to 11 patients with severe von Willebrand disease and unmeasurable levels of plasma vWF. In comparison with the historical data obtained infusing hemophiliacs in the same conditions, monoclonally-purified FVIII had a significantly shorter half-life and faster clearance from plasma but similar in vivo recovery and volume of distribution. Two additional patients with severe von Willebrand disease were also infused with recombinant FVIII totally devoid of vWF. Half-life was very short and in vivo recovery low, with a larger volume of distribution than for monoclonally-purified FVIII. We conclude that in patients with severe von Willebrand disease the small amounts of vWF contained in the monoclonally-purified FVIII concentrate are not sufficient to stabilize infused FVIII, nor to support the normal circulation of endogenous FVIII that these patients produce at a normal rate.

Adolescent↗
PubMed1993

Pharmacokinetics, thrombogenicity and safety of a double-treated prothrombin complex concentrate.

The pharmacokinetic profile, the thrombogenicity and the virus safety of Preconativ, a PCC subjected both to virus removal procedure and dry-heat treatment were studied. Preconativ is produced from plasma pool, negative both for HBsAg and for antibodies to HIV. To further reduce the risk of virus transmission, the manufacturing process includes hydrophobic gel chromatography and dry-heat treatment at +68 degrees C for 48 hours. Nine patients with hemophilia B participated in a single dose, pharmacokinetic study. The decay curves of factor IX clotting activity were evaluated by model-independent methods. The Clearance and the Mean Residence Time were very similar to those previously reported for untreated PCC. The Volume of Distribution Area and In Vivo Recovery resulted inversely correlated and respectively larger and smaller than those of untreated PCC. A slight fall in platelet count and Antithrombin III level and an increase of Beta-Thromboglobulin and Fibrinopeptide A concentration were found, indicating a clear-cut activation of the coagulation process during the first hours following Preconativ administration. Seven patients (2 of the ones enrolled in the pharmacokinetic study) were completely fulfilling the SSC-ISTH criteria for virus safety prospective study. The follow up of these patients did not show any transaminases elevation or seroconversion against HBV, HCV or HIV. These findings did not change over a 3-5 year follow up in 3 out of 7 patients, repeatedly infused with Preconativ.

Adolescent↗
PubMed1993

Prospective study of the evaluation of hepatitis C virus infectivity in a high-purity, solvent/detergent-treated factor VIII concentrate: parallel evaluation of other markers for lipid-enveloped and non-lipid-enveloped viruses. The Ad Hoc Study Group of the Fondazione dell'Emofilia.

This prospective study was carried out with the aim of evaluating the efficacy of solvent/detergent inactivation of the hepatitis C virus (HCV) as applied to a chromatographic factor VIII concentrate. In parallel, the markers for other viruses, either lipid-enveloped (human immunodeficiency virus types 1 and 2 [HIV-1 and -2] and hepatitis B virus [HBV]) or non-lipid-enveloped viruses (such as B19 parvovirus and hepatitis A virus [HAV]) were evaluated. The study included 14 hemophilia centers, which enrolled 36 previously untreated patients (median age, 3 years; range, 1-56). The length of follow-up was 12 months, during which HCV (first- and second-generation assays and recombinant immunoblot assay), HIV-1 and -2, HBV, HAV (IgG and IgM), and parvovirus (IgG and IgM) antibodies, as well as alanine aminotransferase values were evaluated. Thirty-one patients were analyzable; none seroconverted for HCV, HBV, or HIV after exposure to a total of 165,000 IU of factor VIII (41 different lots). In one patient, alanine aminotransferase values rose to 167 mU per mL, 6 weeks after the first concentrate infusion, and this patient seroconverted for HAV 1 week later. Furthermore, 10 patients seroconverted for parvovirus during follow-up. This study suggests that the solvent/detergent method of virus inactivation is efficient in relation to lipid-enveloped blood-borne viruses but not in relation to non-lipid-enveloped viruses.

Adolescent↗
PubMed1993

Prognostic value of a novel circulating serum 90K antigen in HIV-infected haemophilia patients.

We evaluated the prognostic role of a novel tumour-associated antigen, termed 90K, in a cohort of HIV+ asymptomatic haemophilia patients with known duration of seropositivity and median follow-up of about 7 years. The circulating levels of 90K are higher in HIV+ asymptomatic patients than HIV- controls. The antigen levels remain quite stable over time in non-progressing patients, while they steadily rise in patients evolving to ARC/AIDS. Baseline high 90K levels are predictive of faster progression to ARC/AIDS and shorter survival. We conclude that an elevated 90K serum level is a predictor of poor prognosis in HIV+ asymptomatic haemophiliacs.

AIDS-Related Complex↗
PubMed1992

Pharmacokinetic properties of recombinant factor VIII compared with a monoclonally purified concentrate (Hemofil M). The Recombinate Study Group.

A recombinant FVIII preparation, Recombinate, was compared with a high-purity plasma-derived concentrate, Hemofil M, in 47 hemophilia A patients in a cross-over evaluation of pharmacokinetic properties. The recombinant material showed a significantly lower clearance, volume of distribution, and higher in vivo recovery, but a similar half-life to the plasma-based product. In a comparison with reported data from other standard concentrates, the recombinant preparation exhibited potentially better pharmacokinetic properties in that its clearance was slower and its half-life was longer. We conclude that the recombinant DNA method of preparation does not adversely affect the biological and pharmacological characteristics of the factor VIII molecule.

Adolescent↗
PubMed1992

Pharmacokinetics of two pasteurized factor VIII concentrates by different and multicenter assays of factor VIII activity.

We assessed the pharmacokinetic characteristics of a new high-purity pasteurized FVIII concentrate in comparison with an intermediate purity pasteurized concentrate, produced by the same manufacturer. The study was designed as a cross-over single-dose pharmacokinetic investigation in 8 non-bleeding patients with severe hemophilia A. All patients were given 25 IU/kg of each of the two concentrates, with an interval of at least one week between the two administrations. Decay curves were assessed by collecting 10 serial blood samples over 36 hours following the end of infusion. The concentration of Factor VIII in blood samples was determined in triplicate in three different laboratories using each of the following assay methods: a one-stage clotting assay, a two-stage clotting assay, and a two-stage chromogenic-peptide substrate assay. All pharmacokinetic parameters were calculated by model-independent methods. The two products were found to differ significantly both in the clearance, which was on average 13.8% lower for Haemate P, and in the in-vivo recovery, which was 11.7% lower for Factor VIII:C P on the average. In comparison with previous pharmacokinetic data obtained from other heated Factor VIII concentrates, the clearance of Haemate P was found to be significantly slower, while the half-life of both products was longer. No differences were observed in the Vd-area. These findings indicate that the purification procedures to which both products are subjected do not increase the in-vivo rate of plasma disappearance of Factor VIII.

Adolescent↗
PubMed1992

Immune status of asymptomatic HIV-infected hemophiliacs: randomized, prospective, two-year comparison of treatment with a high-purity or an intermediate-purity factor VIII concentrate.

It has been postulated that high-purity factor VIII (FVIII) concentrates, since they contain less alloantigenic proteins than intermediate-purity concentrates, might cause lesser deterioration of the immune systems of hemophilic patients infected with the human immunodeficiency virus (HIV). To evaluate this hypothesis, we have prospectively compared T-lymphocytes subsets and delayed hypersensitivity reactions to skin tests in 17 asymptomatic HIV-positive hemophiliacs randomly assigned to continue treatment with an intermediate-purity concentrate with those of 16 hemophiliacs changed to a high-purity concentrate. For both groups, during the 24-month follow-up period CD4 cell counts showed similar rates of fall from baseline values. There was also no difference in the number of patients anergic to skin tests. Three patients treated with the intermediate purity concentrate and one treated with the high-purity concentrate developed symptoms of HIV infection. On the whole, no striking benefit is conferred to the immune status of asymptomatic HIV-positive hemophiliacs by using this high-purity concentrate for 2 years.

Adolescent↗
PubMed1992

Human parvovirus B19 infection in hemophiliacs first infused with two high-purity, virally attenuated factor VIII concentrates.

Human parvovirus B19 can be transmitted by coagulation factor concentrates and is highly resistant to virucidal methods. To evaluate whether the additional removal of virus by chromatographic methods during the manufacture of high-purity concentrates reduces the risk of B19 transmission, we have prospectively evaluated the rate of anti-B19 seroconversion in two groups of susceptible (anti-B19 negative) hemophiliacs infused with high-purity, heated (pasteurized) or solvent-detergent-treated factor VIII concentrates. Both products infected a relatively high proportion of patients (nine of 20).

Detergents↗
PubMed1992

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↗
PubMed1992

Human parvovirus B19 in clotting factor concentrates: B19 DNA detection by the nested polymerase chain reaction.

The presence of B19 parvovirus in plasma from blood donors is seldom demonstrable, but clotting factor concentrates, prepared from large plasma pools, may be able to transmit B19 virus infection, and the effectiveness of different chemical and physical treatment to inactivate this virus is not yet known. In this study we report on the detection of B19 DNA in 25 clotting factor concentrates, prepared by a variety of procedures of purification and inactivation; dot blot hybridization and Southern blot hybridization assays, as well as a 'nested' polymerase chain reaction (PCR) have been employed. Nine out of 25 products were B19 DNA positive by PCR, whereas only two gave positive results by hybridization techniques. B19 DNA positive concentrates have been found in 'untreated' products but also in some solvent/detergent or steam-treated products and even in monoclonal purified concentrates. PCR may be useful for the screening of blood products to be used in immunocompromised haemophiliacs, particularly in HIV positive subjects, at risk of severe chronic anaemia following B19 infection.

Base Sequence↗
PubMed1992

Suppression of autoantibodies to factor VIII and correction of factor VIII deficiency with a combined steroid-cyclophosphamide-porcine factor VIII treatment in a patient with rheumatoid arthritis.

The presence of autoantibodies against factor VIII is an unusual but serious complication in rheumatoid arthritis. We describe the case of a patient who developed this kind of complication, with spontaneous bleeding and marked changes in the haematological parameters, that was unsuccessfully treated with a high dose of intravenous gammaglobulin. Subsequently, combined therapy with porcine factor VIII concentrate, cyclophosphamide and steroids led to the disappearance of the anti-factor VIII autoantibodies.

Aged↗
PubMed1992

Hemodialysis with defibrotide: effects on coagulation parameters.

In a crossover study conducted with eight uremic patients maintained on hemodialysis, the Authors compared the effects of heparin (100 IU/kg at the start of dialysis) and defibrotide (400 mg at the start, repeated at 2 hours of ongoing dialysis) on the parameters of blood coagulation (VIII:C, AT III, TAT, PC antigen and activity, PS, and FPA), each being assessed before dialysis and at 2, 3 and 4 hours of the ongoing procedure. Heparin-assisted dialysis resulted in a significant rise of VIII:C and AT III; with defibrotide, instead, there was evidence of thrombin activation (increased FPA and TAT). PC levels were raised with both dialysis modalities; however, PC activity and PS levels were increased only in defibrotide-assisted dialysis. There were no adverse reactions or evidence of fibrin formation. These results confirm the antithrombotic activity of defibrotide in the course of dialysis and indicate that this action is independent of thrombin neutralization.

Antithrombin III↗
PubMed1991

Reproducibility of one-stage, two-stage and chromogenic assays of factor VIII activity: a multi-center study.

This study was aimed at assessing the reproducibility of Factor VIII assays between different laboratories using the same reagents. A total of 176 post-dose plasma samples were obtained from 8 Italian subjects with hemophilia-A treated with a single dose of Factor VIII concentrates. Three laboratories (in FRG, Italy, and Sweden) participated in the study. Frozen aliquots of each sample were dispatched to each of the laboratories, where the aliquots were assayed using the same one-stage, two-stage and chromogenic methods. The one-stage and the chromogenic methods were well reproducible between the three centers: pairwise correlation analyses yielded r-values ranging from 0.88 to 0.91 for the one-stage method and from 0.91 to 0.96 for the chromogenic method. The agreement between these two assays was less evident in samples with activity below 200 IU/L in which the one-stage gave, on average, higher Factor VIII concentrations than those provided by the chromogenic method. The two-stage method was not well reproducible, and the pairwise r-values ranged from 0.48 to 0.73. Our study emphasises the need to develop multi-center quality control programs to verify the reproducibility of Factor VIII assays.

Adolescent↗
PubMed1991

Comparative evaluation of the pharmacokinetics of three monoclonal factor VIII concentrates.

Hemofil M, Monoclate HT, and Monoclate P are high-purity Factor VIII concentrates, obtained from plasma by immunoaffinity chromatography with monoclonal antibodies specific for Factor VIII (Hemofil M) or von Willebrand Factor (Monoclate HT and Monoclate P). The concentrates are subjected to virucidal treatments: a solvent/detergent method (TNBP/Na-cholate) for Hemofil M, heating in the lyophilized state and in solution (pasteurization) for Monoclate HT and Monoclate P, respectively. Since these differences in the manufacturing process might result in different in vivo characteristics of the concentrates, we compared their in vivo behavior in a cross-over, single-dose, pharmacokinetic study performed in 10 non-bleeding patients with severe hemophilia A. The experimental conditions (Factor VIII dose, number and timing of blood sampling, Factor VIII assay methods, calculation of pharmacokinetic parameters) were identical for the three products. The results showed that the clearance, the mean residence time, and the volume of distribution did not differ among the three products.

Factor VIII↗