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M Schiavoni

Publications and source records attributed to M Schiavoni.

At least 19 recordsLinked to original sources
PubMed2007

Current use of by-passing agents in Europe in the management of acute bleeds in patients with haemophilia and inhibitors.

The ultimate goal of treatment for patients with inhibitory antibodies should be to permanently eradicate the inhibitor by immune tolerance induction therapy (ITI). However, ITI procedures fail in a substantial number of patients and in many countries ITI is not even offered owing to its high cost. How patients with inhibitors are managed in different European countries is evaluated with a special focus on the use of by-passing agents, i.e. recombinant FVIIa (rFVIIa) and activated prothrombin complex concentrates (aPCC), as well as the type of monitoring performed. Investigators from 22 large haemophilia centres participating within the network of the European Haemophilia Therapy Standardisation Board (EHTSB) were asked to complete a questionnaire. rFVIIa was routinely used in all centres for both children and adults at dosages ranging from 90 to 250 mug kg(-1) at an interval of 2-4 h. aPCC was used in 85% of the centres in adults and in 25% of the centres in children with haemophilia A at dosages of 50-100 IU kg(-1) every 6-12 h. The corresponding figures for children and adults with haemophilia B were 40% and 15% of the centres, respectively. Higher dosages of both agents were considered in the case of life-threatening bleeds. General recommendations were developed, based on the information provided by the survey. The results clearly indicate the need for well-designed comparative studies to optimize the use of by-passing agents.

Acute Disease↗
PubMed2006

Current European practice in immune tolerance induction therapy in patients with haemophilia and inhibitors.

The management of patients with inhibitors is an important challenge in haemophilia care. The lack of randomized controlled trials means that clinical decisions are generally based on subjective opinions, and purchasers' attention is likely to focus on the costs of treatment. In order to assess the current management of inhibitor patients and use of immune tolerance induction therapy (ITI) in Europe, we performed a survey within a European network of 21 comprehensive care centres from 14 countries (the European Haemophilia Therapy Standardisation Board). The survey identified a total of 381 patients with inhibitors attending the centres, 211 (55.4%) of whom had never been exposed to ITI. Between 1998 and 2003, the centres performed 233 procedures and 114 (48.9%) were successful. The survey demonstrated that dosing, which is the time to start and stop the ITI, the type of concentrate to use and the definition of success varied among the centres. Well-designed trials are warranted to guide decision-making, but in the absence of these studies we have developed consensus guidance for the management of inhibitor patients based on current clinical practice, as identified by the survey, and review of the literature.

Adult↗
PubMed2004

Patients with type 3 severe von Willebrand disease are not protected against atherosclerosis: results from a multicenter study in 47 patients.

BACKGROUND: The results of a number of studies in pigs and mice suggest that absence of von Willebrand factor (vWF) protects against the development of atherosclerosis. We studied whether patients with a complete deficiency of vWF (type 3 von Willebrand disease [vWD]) develop fewer atherosclerotic vessel wall changes than healthy controls. METHODS AND RESULTS: This study included 47 individuals with type 3 vWD and 84 healthy controls. Early atherosclerotic changes were assessed by measuring the thickness of the intima-media in the carotid and femoral arteries by B-mode ultrasonography. Advanced atherosclerotic changes were quantified by summing the maximal thickness of atherosclerotic plaques in the carotid and femoral arteries and were expressed as a plaque score. Established risk factors were determined to adjust for possible differences between the groups. We found no substantial difference in intima-media thickness between vWD patients and controls (adjusted difference for carotid artery 0.007 mm, 95% CI -0.022 to 0.036 mm; femoral artery 0.069 mm, 95% CI -0.056 to 0.19 mm). Similar proportions of patients and controls had atherosclerotic plaques (19% and 17%, respectively). No difference was found in the plaque score between groups (adjusted difference -0.22 mm, 95% CI -0.69 to 0.26). Among vWD patients, we found no effect of treatment with vWF concentrates on intima-media thickness or plaque score. CONCLUSIONS: The results of this study indicate that vWF does not play a substantial role in human atherogenesis.

Adult↗
PubMed2003

Phase control of directed diffusion in a symmetric optical lattice.

We demonstrate the phenomenon of directed diffusion in a symmetric periodic potential. This has been realized with cold atoms in a one-dimensional dissipative optical lattice. The stochastic process of optical pumping leads to a diffusive dynamics of the atoms through the periodic structure, while a zero-mean force which breaks the temporal symmetry of the system is applied by phase modulating one of the lattice beams. The atoms are set into directed motion as a result of the breaking of the temporal symmetry of the system.

Journal Article↗
PubMed2003

Rayleigh scattering and atomic dynamics in dissipative optical lattices.

We investigate Rayleigh scattering in dissipative optical lattices. In particular, following recent proposals [S. Guibal, Phys. Rev. Lett. 78, 4709 (1997)]; C. Jurczak, Phys. Rev. Lett. 77, 1727 (1996)]], we study whether the Rayleigh resonance originates from the diffraction on a density grating and is therefore a probe of transport of atoms in optical lattices. It turns out that this is not the case: the Rayleigh line is instead a measure of the cooling rate, while spatial diffusion contributes to the scattering spectrum with a much broader resonance.

Journal Article↗
PubMed2002

Brillouin propagation modes in optical lattices: interpretation in terms of nonconventional stochastic resonance.

We report the first direct observation of Brillouin-like propagation modes in a dissipative periodic optical lattice. This has been done by observing a resonant behavior of the spatial diffusion coefficient in the direction corresponding to the propagation mode with the phase velocity of the moving intensity modulation used to excite these propagation modes. Furthermore, we show theoretically that the amplitude of the Brillouin mode is a nonmonotonic function of the strength of the noise corresponding to the optical pumping, and discuss this behavior in terms of nonconventional stochastic resonance.

Journal Article↗
PubMed2001

Pharmacokinetic evaluation of recombinant, activated factor VII in patients with inherited factor VII deficiency.

BACKGROUND AND OBJECTIVES: Recombinant factor VIIa (rFVIIa) has been widely used in the treatment of bleedings occurring in hemophiliacs with inhibitors. Very few reports exist on the use of rFVIIa in patients with inherited FVII deficiency. Pharmacokinetic studies on rFVIIa have been performed exclusively in hemophiliacs, patients with cirrhosis or volunteers pretreated with acenocoumarol. The aim of this study was to evaluate the kinetics of rFVIIa in patients naturally deficient of FVII. DESIGN AND METHODS: A single dose kinetic study with rFVIIa was performed in 5 patients affected by severe congenital deficiency of factor VII in order to evaluate the true kinetic parameters of rFVIIa without the interference of FVII. Two dosages, 15 and 30 microg/kg, were used in a crossover schedule. FVII:C and FVIIa concentration/time curves were analyzed by a model-independent method. Antithrombin (AT), prothombin fragment 1+2 (F1+2) and tissue factor pathway inhibitor (TFPI) were assayed. RESULTS: No differences emerged between the dosages with respect to dose-independent parameters [total body clearance (CL), volume of distribution area (VdArea), mean residence time (MRT)]. No significant changes of AT, TFPI, and F1+2 were observed. Comparing the results with those of other studies performed in adult hemophiliacs, in patients affected by cirrhosis or in volunteers on oral anticoagulant therapy (OAT), CL and VdArea of rFVIIa were definitely higher and in vivo recovery was lower. INTERPRETATION AND CONCLUSIONS: These findings suggest that the kinetics of rFVIIa are not dose-dependent. In the absence of FVII, the changes of VdArea and CL may be in agreement with a mechanism of competition between FVII and rFVIIa for tissue factor binding.

Adult↗
PubMed1997

Transmission of parvovirus B19 by coagulation factor concentrates exposed to 100 degrees C heat after lyophilization.

BACKGROUND: Double inactivation by solvent/detergent treatment plus heating at 100 degrees C for 30 minutes after lyophilization has been adopted to improve viral safety of factor VIII and factor IX concentrates, particularly with respect to non-lipid-enveloped viruses. The aim of this study was to evaluate the safety of concentrates exposed to these virucidal methods. STUDY DESIGN AND METHODS: Twenty-six previously untreated hemophiliacs, 19 with factor VIII deficiency and 7 with factor IX deficiency, were investigated in a prospective multicenter study over a 12-month follow-up period by the use of serologic and virologic markers for lipid- and non-lipid-enveloped viruses (human immunodeficiency virus types 1 and 2; hepatitis A, B, and C viruses; B19 parvovirus antibodies; and B19 DNA). Overall, 270,000 U of factor VIII and 102,000 U of factor IX concentrate were administered during the study period. RESULTS: None of the 26 patients seroconverted for human immunodeficiency virus or hepatitis C virus. Hepatitis B virus markers remained negative in the 10 unvaccinated hemophiliacs. No hepatitis A virus seroconversion occurred among 17 susceptible patients. B19 seroconversion (IgM) and B19 viremia were observed within 2 weeks of the first concentrate infusion in 8 of 15 susceptible patients, 5 of 11 treated with factor VIII and 3 of 4 with factor IX concentrate. CONCLUSION: This prospective study indicates that very high temperatures applied to lyophilized concentrates appear to prevent the transmission of hepatitis A virus to hemophiliacs. However, B19 parvovirus still contaminates concentrates despite the use of this robust virucidal method.

Adolescent↗
PubMed1996

Use of recombinant factor VIIa (NovoSeven) in the treatment of two patients with type III von Willebrand's disease and an inhibitor against von Willebrand factor.

Two siblings affected by type III von Willebrand's disease with precipitating alloantibodies against von Willebrand's factor (vWF) and not susceptible to treatment with factor VIII/vWF concentrates received recombinant activated factor VII for oral surgery. This therapy, combined with antifibrinolytic drugs and local application of fibrin glue, seems to be effective and safe. It may be considered a promising approach to the management of this rare condition.

Adolescent↗
PubMed1996

Safety profile of porcine factor VIII and its use as hospital and home-therapy for patients with haemophilia-A and inhibitors: the results of an international survey.

A multicentre retrospective survey was conducted to re-assess the use of porcine factor VIII (HYATE:C), its side effects and the selection of patients for regular or home-therapy. 15,152,000 units of HYATE:C were used by 154 patients. The median inhibitor cross-reactivity to porcine VIIIC of 137 patients was 15%, 27% of patients lacking cross-reactivity. An absent, intermediate or brisk specific antiporcine anamnestic response was observed in 29, 40 and 31% of patients respectively. Seven patients were treated on-demand as home-therapy for a median 6.2, range 1.5-13 years, 23 further patients were treated regularly in hospital for a median of 3, range 2-7 years. This group used 8,319,000 U of porcine VIIIC for 2,000 bleeding episodes. The incidence of transfusion reactions was 0.001%, 0.64% and 2.3%, for domiciliary infusions, infusions in multiply treated in-patients, and unselected in-patient infusions, respectively. The risk of reactions was dose-related. A post-infusion fall in platelet count was common, but usually transient and clinically insignificant. This was also dose-related (r = -0.64, p = 0.002). Marked reductions in platelet count were occasionally seen, usually with intensive replacement therapy. The relative lack of side effects observed amongst patients treated at home is attributable to the low, median 33 U/kg, dose used by this group. A subgroup of inhibitor patients, identifiable by their absent or modest anamnestic response to porcine factor VIII may be treated regularly and safely with this product in small doses, over a period of years.

Animals↗
PubMed1994

Prevalence of infection with the hepatitis C virus among Italian hemophiliacs before and after the introduction of virally inactivated clotting factor concentrates: a retrospective evaluation.

In July 1985, all coagulation factor concentrates were withdrawn from the market in Italy and replaced with virally inactivated concentrates. A retrospective survey comparing the prevalence of the antibody to the hepatitis C virus (anti-HCV) in hemophiliacs multitransfused with nonvirally inactivated concentrates until 1985 with that in previously untreated hemophiliacs transfused exclusively with virally inactivated concentrates since 1985 has been conducted in 9 Italian hemophilia centers. The centers, which follow about one-fourth of all the Italian hemophiliacs, provided information about 708 patients infused for the first time before 1985 (group A) and 80 patients infused for the first time between 1985 and 1991 (group B). The prevalence of anti-HCV was 83% (591/708) in group A and 6% (5/80) in group B. For the 5 anti-HCV-seropositive patients from group B, dry heating, hydrophobic interaction chromatography plus dry heating (2 patients), hot vapor and pasteurization were the virucidal methods used for the concentrates implicated in HCV transmission. In the case associated with pasteurization, there is the possibility of intrafamilial transmission of HCV. It appears from this retrospective analysis that there has been a substantial reduction in the risk of HCV transmission since the adoption of virucidal methods. However, these methods do not eliminate completely the risk, which might be further reduced by the recent adoption of anti-HCV screening for plasma donations used to manufacture concentrates.

Blood Coagulation Factors↗
PubMed1994

The outbreak of hepatitis A in Italian patients with hemophilia: facts and fancies.

To determine whether an outbreak of hepatitis A that occurred in 52 Italian hemophiliacs was acquired through the infusion of contaminated factor VIII or through environmental enteric transmission, a case-control study of the first 29 infected patients was carried out. Case patients were neither more nor less likely than controls (hemophiliacs without HAV infection) to have traveled to high-risk countries, consumed raw shellfish or had contact with persons with jaundice. The case patients, however, were more likely than controls to have received a factor VIII concentrate treated with solvent-detergent and to have had larger infusions of the concentrate during the presumed HAV incubation period. In the PCR analysis of HAV sequences from implicated lots of factor VIII, HAV sequences were found in 5 of 12 lots of factor VIII implicated in the outbreak. Three different strains of HAV were recovered, suggesting that lots were not contaminated from the same plasmapheresis donor. To obtain molecular evidence that the HAV detected in the factor VIII preparations was responsible for transmission of HAV, serial serum samples from two patients were tested for HAV gene sequences and compared with those of the implicated lots. The genomic sequences of HAV obtained for two matched sets of factor VIII and recipient serum samples were identical within each set, but different for the two sets.

Adolescent↗
PubMed1993

Accelerated schedule of hepatitis B vaccination in patients with hemophilia.

Early development of immunity after hepatitis B vaccination is particularly important for patients such as hemophiliacs, at high risk for acquiring hepatitis B from potentially infectious plasma-derived concentrates. The purpose of this study was to evaluate whether or not protective antibody titers could be achieved quickly and maintained in hemophiliacs by an accelerated vaccination schedule. A yeast-recombinant hepatitis B vaccine (Engerix B, SKF Ritt) was given subcutaneously in the deltoid region and repeated 2 and 6 weeks later to 85 hemophiliacs negative for hepatitis B virus (HBV) markers. After the first 22 patients had been enrolled, a modification of the schedule involving a fourth booster dose 24 weeks after the first dose of vaccine was applied to the next 63 consecutive vaccines. Fifty-three percent of vaccinees had antibody titers to hepatitis B surface antigen (anti-HBs > or = 10 mlU/ml) by week 6, even though the mean titers of anti-HBs were somewhat lower than those achieved historically in normal individuals. The protection rate had increased to 87% by week 10, one month after the third dose of vaccine, and to 93% by week 24. One year after starting vaccination, the rate for the vaccinees who did not receive the fourth booster dose was 71%, and 96% for those who did receive the fourth dose, with only 2 patients not responding despite the booster dose. It is concluded that even though the accelerated schedule of immunization produced rapidly high rates of protective antibody titers, a booster dose is required to obtain higher titers and provide more persistent immunity.

Adolescent↗
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↗