Mortality and causes of death in Italian persons with haemophilia, 1990-2007.

Although a number of studies have analysed so far the causes of death and the life expectancy in haemophilic populations, no investigations have been conducted among Italian haemophilia centres. Thus, the aim of this study was to investigate mortality, causes of deaths, life expectancy and co-morbidities in Italian persons with haemophilia (PWH). Data pertaining to a total of 443 PWH who died between 1980 and 2007 were retrospectively collected in the 30 centres who are members of the Italian Association of Haemophilia Centres that chose to participate.

Residual factor VII activity and different hemorrhagic phenotypes in CRM(+) factor VII deficiencies (Gly331Ser and Gly283Ser).

Two cross-reacting material-positive (CRM(+)) factor VII (FVII) mutations, associated with similar reductions in coagulant activity (2.5%) but with mild to asymptomatic (Gly331Ser, c184 [in chymotrypsin numbering]) or severe (Gly283Ser, c140) hemorrhagic phenotypes, were investigated. The affected glycines belong to structurally conserved regions in the c184 through c193 and c140s activation domain loops, respectively.

ERGIC-53 gene structure and mutation analysis in 19 combined factors V and VIII deficiency families.

Combined factors V and VIII deficiency is an autosomal recessive bleeding disorder associated with plasma levels of coagulation factors V and VIII approximately 5% to 30% of normal. The disease gene was recently identified as the endoplasmic reticulum-Golgi intermediate compartment protein ERGIC-53 by positional cloning, with the detection of two founder mutations in 10 Jewish families. To identify mutations in additional families, the structure of the ERGIC-53 gene was determined by genomic polymerase chain reaction (PCR) and sequence analysis of bacterial artificial chromosome clones containing the ERGIC-53 gene.

Knowledge of HIV/AIDS and emotional adjustment in a cohort of men with haemophilia and HIV infection: final report.

This study presents the final report of a long-term psychological assessment of men with haemophilia and HIV infection. The knowledge, emotional impact regarding HIV infection and prospective changes over time and the need for psychological support were evaluated. The study group comprised 118 men with haemophilia, 66 HIV seropositive and 52 seronegative, from the Haemophilia Centres in Bari, Florence, Milan and Naples.

Mutations in the ER-Golgi intermediate compartment protein ERGIC-53 cause combined deficiency of coagulation factors V and VIII.

Combined deficiency of factors V and VIII is an autosomal recessive bleeding disorder resulting from alterations in an unknown gene on chromosome 18q, distinct from the factor V and factor VIII genes. ERGIC-53, a component of the ER-Golgi intermediate compartment, was mapped to a YAC and BAC contig containing the critical region for the combined factors V and VIII deficiency gene. DNA sequence analysis identified two different mutations, accounting for all affected individuals in nine families studied.

A prospective multicenter study of hepatocellular carcinoma in italian hemophiliacs with chronic hepatitis C. The Study Group of the Association of Italian Hemophilia Centers.

To assess the risk factors, natural history, and eligibility for curative treatment of early-detected hepatocellular carcinoma (HCC), 385 hemophiliacs who were treated with blood or plasma derivates for at least 10 years and had persistently elevated aminotransferase values underwent an annual screening with an abdominal ultrasound examination and measurement of the serum alpha-fetoprotein (AFP) level. Of these, 355 had serum antibody to hepatitis C virus (anti-HCV), 29 had anti-HCV and hepatitis B surface antigen (HBsAg), and one had HBsAg alone; 141 had serum antibody to human immunodeficiency virus (anti-HIV). During 48 months of follow-up study, six patients developed HCC.

Thrombotic events during oral anticoagulant treatment: results of the inception-cohort, prospective, collaborative ISCOAT study: ISCOAT study group (Italian Study on Complications of Oral Anticoagulant Therapy).

The paper reports on rate and type of thrombotic events occurring during the observational, prospective, inception-cohort, multicenter ISCOAT study. 2,745 unselected, daily practice patients, consecutively referring to 34 Italian anticoagulation clinics to monitor the oral anticoagulant treatment, were included in the study from beginning of their first anticoagulant course. During a total follow-up of 2,011 patient-years of treatment 70 thrombotic events (3.

Acquired haemophilia: experience of two Italian centres with 17 new cases.

Acquired haemophilia is a rare but often catastrophic haemorrhagic disorder associated with a high mortality rate. No single therapeutic approach has been consistently successful and clinical experience remains mainly anecdotal. This report describes 17 new cases diagnosed at two Italian haemophilia centres between 1979 and 1995.

[Hemorrhagic complications of oral anticoagulant therapy: results of a prospective multicenter study ISCOAT (Italian Study on Complications of Oral Anticoagulant Therapy)].

Background: To assess the incidence of bleeding complications during oral anticoagulant therapy (OAT) in a population of patients representative of daily practice in Italian anticoagulation clinics.

Design: prospective, inception-cohort, multicentre.

Setting: Thirty-four anticoagulation clinics federated in the Italian Federation of Anticoagulation Clinics.

Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT). Italian Study on Complications of Oral Anticoagulant Therapy.

Background: Bleeding is the most serious complication of the use of oral anticoagulation in the prevention and treatment of thromoboembolic complications. We studied the frequency of bleeding complications in outpatients treated routinely in anticoagulation clinics.

Methods: In a prospective cohort from thirty-four Italian anticoagulation clinics, 2745 consecutive patients were studied from the start of their oral anticoagulation (warfarin in 64%, acenocourmarol in the rest).

Study of complement-mediated anaphylaxis in humans. The role of IgG subclasses (IgG1 and/or IgG4) in the complement-activating capacity of immune complexes.

The role of Ig classes and subclasses in complement activation has been investigated both in vitro and in experimental animals, but not in humans. This study was conducted to determine the immunologic events of post-transfusion anaphylaxis in humans, and the effects of immune complexes of different IgG subclass compositions on complement activation. The ability of immune complexes containing mixed IgG1 and IgG4 or IgG4 Ab only to activate complement was investigated in two patients with von Willebrand's disease (a congenital bleeding disorder).

Long-term immunogenicity and safety of an inactivated hepatitis A vaccine in haemophilic patients.

As a consequence of recent outbreaks of HAV infection by blood products, 91 patients, haemophiliacs and subjects with bleeding disorders (10 of whom were also anti-HIV positive) susceptible to HAV infection received a formalin-inactivated hepatitis A vaccine (HAVRIX 720 Elisa Units, SmithKline Beecham). Subcutaneous injections were given in the deltoid region at 0, 1 and 6 months. The seroconversion rates and litres, expressed in GMT IU/1, were determined at 1, 2, 6, 7, 12, 18 and 24 months.

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.

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.

Psychological status of men with haemophilia and HIV infection: two-year follow-up.

This study aimed to assess the psychological status of men with haemophilia and HIV infection and to monitor changes in psychlogical status over time, in order to evaluate the need for psychological support. The study included 24 HIV seropositive men and a control group of 21 HIV seronegative men who attended the Haemophilia Centre in Bari (Italy). Subjects underwent psychological tests (STAl-Y: State and Trait Anxiety Inventory; SDS: Self-Rating Depression Scale) and completed a questionnaire on the emotional impact of AIDS.

Virology of the hepatitis A epidemic in Italy.

We studied the virologic aspects of a hepatitis A epidemic that occurred among hemophilia patients in Italy between 1989 and 1992. Twelve lots of factor VIII concentrate manufactured by the solvent-detergent chromatographic technique and suspected of contamination by the hepatitis A virus (HAV) were analyzed by a two-step, nested polymerase chain reaction (PCR) procedure. PCR was applied to 1-ml samples of factor VIII concentrate and 100-microliters serial serum samples available from 2 patients.

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).

Transmission of hepatitis A to patients with hemophilia by factor VIII concentrates treated with organic solvent and detergent to inactivate viruses. The Italian Collaborative Group.

Objective: To determine whether an outbreak of hepatitis A virus (HAV) infection that occurred in 52 patients with hemophilia in Italy was acquired through infusion of contaminated factor VIII or through environmental enteric transmission.

Design: A case-control study and a molecular analysis of HAV sequences from implicated lots of factor VIII and from infected patients.

Patients: The first 29 patients with hemophilia and jaundice in whom hepatitis A developed were compared with one to three matched controls with hemophilia but no jaundice.

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.