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M Morfini

Publications and source records attributed to M Morfini.

At least 19 recordsLinked to original sources
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↗
PubMed1991

Early haemostatic modifications following cryopreserved graft infusion.

The nature of the graft used for the rescue of patients undergoing autologous bone marrow transplantation is that of a complex mixture of pharmacological agents and cellular debris known to have a number of effects on the haemostatic system. The present study was undertaken to evaluate the occurrence and the degree of haemostatic alterations during and immediately following graft infusion in 24 patients suffering from haematological malignancies. On day 0, before graft infusion, the majority of patients appeared with laboratory signs of enhanced thrombin generation, platelet activation, and endothelial damage, most likely due to the conditioning regimen. However, the graft infusion per se was accompanied in the short term by a further increment of some parameters indicating a thrombotic risk (as thrombin-antithrombin complex, beta-thrombo globulin, platelet factor four, and von Willebrand factor antigen, together with a concomitant prolongation of partial thromboplastin time and a reduction of prothrombin time. In contrast there was no further modification of antithrombin III or protein C levels nor an increase in fibrinopeptide A levels. We hypothesize that complex interactions between agents contained in the graft mixture and host haemostatic system are involved in the pathogenesis of the haemostatic alterations which followed cryopreserved graft infusion; however, in our series, these were not accompanied by clinical signs of thrombotic or haemorrhagic events.

Antithrombin III↗
PubMed1990

Recurrent mutations and three novel rearrangements in the factor VIII gene of hemophilia A patients of Italian descent.

Hemophilia A (HA), a common inherited bleeding disorder in humans, is due to the deficiency or absence of the factor VIII (FVIII) activity. The cloning of the FVIII gene has made molecular probes available for the characterization of the basic defect in this disease. In this study we describe six different mutations in the FVIII gene detected by DNA analysis of 100 HA patients of Italian descent. In two of them, with a severe clinical picture, we identified two novel deletions, one in the middle of the FVIII gene from exons 7 to 22 and the other encompassing the entire factor VIII gene. Both of these patients produced antibodies to factor VIII. In a patient with mild HA we detected a duplication of exon 13, which is a rearrangement not yet described within the FVIII gene. A possible explanation for the mild phenotype in this patient is that the molecular defect results in the production of an unstable FVIII protein with residual 10% FVIII activity. Screening by Taq I restriction endonuclease detected three mutations that were further characterized by direct sequencing on amplified DNA: a C-T substitution at codon 1960, in exon 18, converting the codon for arginine to a non-sense codon; and a G-A substitution at codon 2228 and 2326, in exons 24 and 26 respectively, resulting in the substitution of glutamine for arginine. All three of these mutations have been previously described. The non-sense mutation and the codon 2228 G-A mutation was found in patients with severe HA, while the codon 2326 G-A mutation was associated with a quite severe condition. These results confirm that the molecular bases of HA are very heterogeneous and provide further evidence that recurrent mutations are not uncommon in this system.

Base Sequence↗
PubMed1990

Cutaneous and plasma fibrinolytic activity in systemic sclerosis. Evidence of normal plasminogen activation.

Eleven patients with systemic sclerosis (SSc) were studied for plasma and cutaneous fibrinolytic activity, residual (potential fibrinolysis) fibrinolytic activity (FA) fo the dermal vessels that is related to the endothelial storage of plasminogen activators that become available due to particular stimuli such as intradermic injection of histamine, and the serum levels of circulating von Willebrand antigen, antithrombin III, plasminogen, beta-thromboglobulin, and platelet aggregate ratio (PAR). Cutaneous FA (autohistographic fibrin film method) appeared normal or increased in non-affected skin, normal in lesional skin, and increased after intradermal (i.d.) injection of 0.1 ml of 0.01% histamine. Monoclonal antibodies directed against the catalytic site of tissue type plasminogen activator completely blocked the fibrinolytic activity, while anti-urokinase antibodies did not abolish the lysis areas. Plasmatic FA, euglobulin lysis time test, (ELT) and the levels of beta-thromboglobulin resulted similar to the controls. A significant increase in von Willebrand Factor VIII antigen (but not of Factor VIII coagulant) was observed in the patients (p less than 0.01). Platelet aggregate ratio, levels of plasma plasminogen and Antithrombin III showed a significant difference (p less than 0.01) when compared with the control subjects. Data suggest that primary injured microvessels in SSc are likely to be arteriolae while venulae could be affected by secondary hypoxia due to the arteriolar damage with consequent release of tissue type plasminogen activator. Therefore, the authors suggest that the fibrinolytic potential is maintained in SSc and that the fibrinolytic therapy should not be used in all patients with SSc but only in those cases with documented exhaustion of plasmatic and/or cutaneous FA.

Adolescent↗
PubMed1990

Etoposide in remission induction of adult acute myeloid leukemia.

96 consecutive acute myelogenous leukemia (AML) patients were analyzed retrospectively with regard to the regimen used for remission induction. 35 patients received daunorubicin for 3 days, cytosine arabinoside and 6-thioguanine for 7 days. 61 were treated with the same regimen but 6-thioguanine was replaced by etoposide. Complete remission was achieved in 57 and 72% of patients, respectively (p = 0.06). In leukemias with monocytic phenotype (M4-M5), the remission rate was significantly higher with the etoposide-containing regimen (p = 0.02). Our findings suggest that the replacement of thioguanine by etoposide could be useful in induction therapy of AML.

Adult↗