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R De Biasi

Publications and source records attributed to R De Biasi.

At least 19 recordsLinked to original sources
PubMed1999

Major surgery for a gastric cancer in a haemophilic with high inhibitor titre successfully performed by the use of recombinant FVIIa.

A total gastrectomy with omentectomy and resection of the distal oesophagus in a 69-year-old haemophilia A patient with high inhibitor of 128 Bethesda units is described. Surgery was successfully performed after infusion of 112 microg kg-1 bw of recombinant FVIIa. Ninety-two microg kg-1 were given thereafter at time intervals of 2 h until 12 h, then every 3 h until 24 h, and every 4 h until 48 h after surgery. Doses were gradually reduced in the following days and finally discontinued on day 28 after surgery. The complete treatment schedule required the administration of a total of 708 mg of recombinant FVIIa. Using this approach, we observed normal haemostasis, and there were no signs of excessive postoperative bleeding or wound haematoma. No clinical side-effects or evidence of systemic activation of coagulation occurred during the treatment. As judged from the clinical course of this major surgery, recombinant FVIIa appears to be highly efficacious and safe and should be used as first line treatment in high titre inhibitor patients with cross-reactivity to porcine factor VIII, undergoing surgery.

Aged↗
PubMed1994

Epidemiology of hemophilia and of HIV infection in Italy. GICC. Gruppo Italiano Coagulopatie Congenite.

To evaluate the incidence and prevalence of hemophilia in Italy and the impact of HIV infection on the Italian hemophiliac population, data from a computerized national registry of patients from 95% of the hemophilia care centers in Italy were analyzed. A total of 4643 patients were included in the registry. The prevalence of hemophilia A was 8.2 per 100,000 males, with no significant regional differences; for hemophilia B the corresponding figure was 1.5 per 100,000. Temporal trends in hemophilia incidence suggest that the diagnosis of mild and moderate hemophilia has improved. The overall HIV prevalence was 26% and was significantly (p < 0.001) higher in patients with hemophilia B (47.1%) compared to those with hemophilia A (26.8%) or other diseases (16.5%). The highest rate of HIV seropositivity was among patients 20-29 years of age. The annual amount of clotting factor concentrates received was significantly (p < 0.001) higher in HIV seropositive patients than in those who were seronegative. Antibody testing was never performed on 10.1% of severely affected patients. The number of patients in the Italian registry was similar to the number that would have been expected based on prevalence estimates from other countries. In comparison with other countries, the prevalence of HIV infection recorded in Italy was lower in persons with hemophilia A, but higher in those with hemophilia B. Our study demonstrates the usefulness of a registry in delineating the epidemiology of hemophilia and in studying risk factors for HIV infection. It also underlines the need for continuing surveillance of this population.

Adult↗
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↗
PubMed1990

Antibody to hepatitis C virus after a vapour-heated factor VIII concentrate. The Study Group of the Fondazione dell'Emofilia.

To evaluate whether or not clotting factor concentrates exposed to virucidal procedures transmitted hepatitis C, sera obtained in 1984-1986 from 27 previously untreated hemophiliacs infused with a vapour-heated factor VIII concentrate were tested retrospectively for the antibody to the hepatitis C virus (anti-HCV). A 2-year-old hemophiliac, negative for anti-HCV before administration of concentrate, seroconverted at week 12 and remained anti-HCV positive thereafter. Both his parents were anti-HCV negative and he had no other household contact. The patient had also become HBsAg positive at week 8 and had at the same time a marked elevation of alanine aminotransferase. His double infection with the hepatitis B and C viruses indicates that hot vapour was not completely effective in inactivating these viruses.

Antibodies, Viral↗
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↗
PubMed1988

Immunogenicity of a recombinant hepatitis B vaccine in hemophiliacs.

Yeast-recombinant vaccines against hepatitis B virus (HBV) are now available, but there is no information about whether or not they are immunogenic in patients with hemophilia and other congenital bleeding disorders. Twenty micrograms of a recombinant vaccine expressing the adw serotype of the hepatitis B surface antigen (HBsAg) were given to 41 patients negative for HBV markers and again after 1 and 6 months. Ten percent of the vaccinees had anti-hepatitis B surface antibody (anti-HBs) responses, with titers of 10 mIU/ml or more, 1 month after the first dose of vaccine. The percentage of anti-HBs-positive patients increased to 54% after the second dose and to 98% after the third dose, with only one non-responder. Hence, the recombinant vaccine was immunogenic, with percentages of seroconversion and anti-HBs titers similar to those achieved with plasma-derived vaccines.

Adolescent↗
PubMed1988

Identification by fast atom bombardment mass spectrometry of Hb Indianapolis [beta 112(G14)Cys----Arg] in a family from Naples, Italy.

We have characterized a beta 112 Arg hemoglobin in an individual from Naples, Italy, with minimal clinical problems. Blood tests revealed only slight reticulocytosis and hemoglobin instability. Furthermore, high value of alkali resistance tests for Hb F were observed. Isoelectricfocusing of globins showed the occurrence of a band migrating between the normal alpha and beta globin chains. The fairly stable variant chain was purified by fast protein liquid chromatography. A mass map of the tryptic digest was obtained by fast atom bombardment mass spectrometry clearly showing that we were dealing with a beta chain variant. However, the peptide 105-120 was missing and two new ones were present, i.e.: 105-112 and 113-120; we assumed these peptides to be generated because of the substitution of 112 Cys with an arginine residue. Further confirmation stemmed from the fast atom bombardment mass spectra of the tryptic digest submitted to a single Edman degradation step and to carboxypeptidase B further hydrolysis. The beta-globin chain variant was thus mass mapped to an extent of about 98%. Such a variant, named Hb Indianapolis, was first reported by Adams et al, as an extremely unstable variant producing the phenotype of a severe beta-thalassemia. Contrary to the findings of the above authors the occurrence of the same variant in a clinically normal individual from a Spanish family has recently been reported. Because the clinical manifestations in the latter case are similar to those observed by us, the conclusion can be drawn that beta 112 Arg hemoglobin is not a biologically unstable variant but should be regarded as belonging to the class of unstable hemoglobins giving rise to only marginal clinical problems.

Adult↗
PubMed1987

Hemophilia A: carrier detection and prenatal diagnosis by DNA analysis.

In this study, we used DNA polymorphisms for carrier detection and prenatal diagnosis of hemophilia A in a large group of Italian families. The restriction fragment length polymorphisms (RFLPs) investigated were the intragenic polymorphic Bc/I site within the factor VIII gene; the extragenic multiallelic Taq I system at the St14 locus; and the extragenic Bg/II site at the DX13 locus. The factor VIII probe was informative in 30%, St14 in 82%, and DX13 in 60% of obligate carriers. The combination of factor VIII-Bc/I and St14-Taq I showed that 91% of obligate carriers were heterozygotes for one or both; with all three probes, only 4% of obligate carriers were noninformative. In families clearly segregating for hemophilia A, RFLP analysis allowed us to define the carrier status for the hemophilia A gene in all 27 women tested. RFLP analysis allowed us to exclude the carrier status in 39 of 45 female relatives of sporadic patients. The combination of RFLP analysis and biological assay of factor VIII allowed us to identify a de novo mutation in the maternal grandfather in 7 of 12 of the families with sporadic cases, for which members of three generations were available for study. Nine of 10 couples requesting prenatal diagnosis provided informative RFLP DNA pattern. Carrier status was excluded in two women, two fetuses were shown to be female, and prenatal diagnosis was carried out in five pregnancies by DNA analysis. Prenatal testing was successful in three instances and failed in two because a sufficient amount of chorionic villous DNA was not obtained for the analysis.

DNA↗
PubMed1986

Hepatitis B vaccination of 113 hemophiliacs: lower antibody response in anti-LAV/HTLV-III-positive patients.

One-hundred thirteen adults and children with hemophilia or other congenital bleeding disorders were vaccinated against the hepatitis B virus. Each patient was given three subcutaneous injections of the vaccine at monthly intervals and then a fourth booster dose 14 months after the first. The vaccine was highly immunogenic, since 111 of 113 patients (98%) produced anti-HBs (10 mIU/ml or more). After the first three vaccine doses and after the booster dose, ten anti-LAV/HTLV-III-positive hemophiliacs produced anti-HBs but had a lower average titer than anti-LAV/HTLV-III-negative hemophiliacs. Of the 23 patients treated with concentrates in the 15 month postvaccination period only, none acquired HBV infection. Of the 50 patients treated with concentrates also in the 6 month prevaccination period, one developed hepatitis B. In summary, the vaccine was highly immunogenic in both children and adults with hemophilia; anti-LAV/HTLV-III-positive patients responded to the vaccine, but the average anti-HBs response was lower; no case of hepatitis B occurred in patients treated with concentrates only in the postvaccination period.

Adolescent↗
PubMed1978

Subunits A and S inheritance in four families with congenital factor XIII deficiency.

Previous studies of the inheritance of the two molecular subunits of fibrin stablizing factor (factor XIII) refer to isolated cases. The present work investigates the hereditary mode of transmission of subunits A and S, measured by the Laurell technique, in seven homozygotes and in 29 heterozygotes belonging to four families with factor XIII deficiency. The results indicate that the homozygotes were devoid of immunologically identifiable A subunit, whereas the heterozygotes could be identified by measuring this protein. The subunit S has been found to be decreased both in homozygous and in heterozygous patients, so that it seems that the two subunits, even if their synthesis is controlled by different genes, are genetically related. The mode of transmission of this disorder, supported by quantitative determinations of plasma subunit A, is autosomal recessive.

Factor XIII↗
PubMed1975

[Hemostatic changes in the course of different chronic hepatopathies].

The following tests were performed in 15 cases of chronic aggressive hepatitis (CAH), 12 of cirrhosis, and 8 of other forms of chronic disease: liver function, thromboelastogram, prothrombin time (PT), partial thromboplastin time (PTT), determination of factors I, II, V, X and XIII, euglobulin and FDP lysis, and platelet count, shape and agglutinability. At least one haemostasis alteration was observed in nearly every case, the most common being in the thromboelastogram, PTT, prothrombin, and platelet shape and agglutinability. Defects were most marked in cirrhosis and comparison with CAH was significant in the case of PT and factor V. Fibrinolysis was increased in 60% of the CAH group and rarely elsewhere. Haemorrhage was noted in 7 cases of cirrhosis and 1 of CAH. On each occasion, it was more dependent on the serious nature of the disease, rather than defective haemostasis.

Adult↗
PubMed1975

Hemostatic abnormalities in chronic aggressive hepatitis and liver cirrhosis.

Hemostatic defects of chronic aggressive hepatitis (CAH), 25 cases, and of liver cirrhosis, 20 cases, were investigated. The following assays were performed: liver function tests, thromboelastogram, prothrombin time (PT), partial thromboplastin time (PTT), factors I, II, V, X, XIII, euglobulin lysis time, fibrinogen degradation products (FDP), platelet count, morphology and agglutinability. High incidence of hemostatic defects was present in both groups. Thromboelastogram, PTT, prothrombin and qualitative platelet abnormalities were most common. On the whole, severity of hemostatic alterations in cirrhosis was more pronounced than that found in CAH, FDPs were increased in more than 50% of the CAH cases and only in a few cirrhotic patients. Bleeding occurred more frequently in cirrhosis (55%) than in CAH (4%) and, within the cirrhotic patients' group, it was associated with a more severe thrombocytopenia.

Adult↗