Variability of treatment modalities and intensity in patients with severe haemophilia A on prophylaxis: Results from the Italian national registry.

BACKGROUND: A shift from a standard to a personalized prophylaxis has been increasingly adopted in patients with severe haemophilia A (SHA). This approach has raised the likelihood of a significant variability in the prophylactic approaches and the relative Factor VIII (FVIII) consumptions. The aim of our study was to assess the treatment variability of SHA patients without inhibitors and on prophylaxis regimen in Italy. MATERIAL AND METHODS: Data reported in the National Registry of Congenital Coagulopathies (NRCC) were analysed to assess treatment distribution within SHA patients without inhibitors, focussing on FVIII consumption in 2017, associated with prophylaxis regimen. The analysis was stratified based on age groups and Italian regions to describe the variability of FVIII consumption in Italy. RESULTS: In 2017, the Registry reported the therapeutic plans of 1068 SHA patients without inhibitors on prophylaxis. The mean (95% CI) individual consumption ranges from 123 127 IU (99 736-146 518) in the age group 0-6 years to 345 000 IU (336 000-354 000) in the age group >20 years. A significant FVIII consumption variability was identified within the adult population. Regions with less than 50 patients reported the higher variability in mean FVIII consumption per patient-year within the different age groups. Similar difference in FVIII consumption variability was reported also in the age groups comparing "low," "middle" and "high" patient volume regions. DISCUSSION: A reliable estimation of FVIII consumption for patients' treatment is necessary to manage and plan the appropriate budget and keep treatment's costs affordable. However, without the implementation of a methodology aiming to assess the overall value produced by these FVIII consumptions, the scenario will keep driven by FVIII consumptions, its costs and the budget available. An effort by haemophilic community, haemophilia treatment centres and institutions is required to develop and share this cultural shift in improving haemophilia management and assessment.

Epidemiological data and treatment strategies in children with severe haemophilia in Italy.

OBJECTIVES: In a period of important therapeutic changes in the field of haemophilia care, we provide updated statistics on children with severe haemophilia (0-12 years of age) in Italy. METHODS: Data presented are from the Italian National Registry of Congenital Coagulopathies (NRCC) - survey 2017. RESULTS: Children with severe Haemophilia A (HA) were 242, those with severe haemophilia B (HB) 48. Prophylaxis was adopted in 92.1% of individuals with severe HA and 88.6% with severe HB. Thirty-nine children (14.8%) were on treatment for inhibitors. FVIII prescribed to children with severe HA represented 11.1% of the total consumption, of which 4.6% was extended half-life (EHL). FIX given to children with HB accounted for 7.2% of the total FIX, of which 19.1% was EHL-FIX. CONCLUSION: The paediatric population analysed is characterized by a great adherence to therapy, so this data may constitute a benchmark for use of new, alternative therapies in the coming years.

New data from the Italian National Register of Congenital Coagulopathies, 2016 Annual Survey.

BACKGROUND: In Italy, the National Register of Congenital Coagulopathies (NRCC) collects epidemiological and therapeutic data from patients affected by haemophilia A (HA), haemophilia B (HB), von Willebrand's disease (vWD) and other rare coagulation disorders. Here we present data from the 2016 annual survey. MATERIALS AND METHODS: Data are provided by the Italian Haemophilia Centres, on a voluntary basis. Information flows from every Centre to a web-based platform of the Italian Association of Haemophilia Centres, shared with the Italian National Institute of Health, in accordance with current privacy laws. Patients are classified by diagnosis, disease severity, age, gender and treatment-related complications. RESULTS: In 2016, the total number of patients with congenital coagulopathies in the NRCC was 10,360: 39.8% of these patients had HA, 31.5% had vWD, 8.5% had HB, and 20.2% had less common factor deficiencies. The overall prevalence of HA and HB was 13.9/100,000 males and 3.0/100,000 males, respectively. The overall prevalence of vWD was 5.4/100,000 inhabitants. During 2016, 126 patients had current alloantibodies to factor VIII (FVIII) or factor IX (FIX) and were under treatment with bypassing agents and/or immune tolerance induction. Overall, 388 patients with a history of alloantibodies were recorded in the NRCC of whom 337 with severe HA and 12 with severe HB. Coagulation factor use, evaluated from treatment plans, was approximately 451,000,000 IU of FVIII for HA patients (7.5 IU/inhabitant), and approximately 53,000,000 IU of FIX for HB patients (0.9 IU/inhabitant). DISCUSSION: The prevalences of HA and HB fall within the ranges reported in more developed countries; the consumption of FVIII and FIX was in line with that of other European countries (France, United Kingdom) and Canada. The NRCC, with its bleeding disorder dataset, is a helpful tool for shaping public health policies, as well as planning clinical and epidemiological research projects.

Italian Registry of Congenital Bleeding Disorders.

In Italy, the surveillance of people with bleeding disorders is based on the National Registry of Congenital Coagulopathies (NRCC) managed by the Italian National Institute of Health (Istituto Superiore di Sanità). The NRCC collects epidemiological and therapeutic data from the 54 Hemophilia Treatment Centers, members of the Italian Association of Hemophilia Centres (AICE). The number of people identified with bleeding disorders has increased over the years, with the number rising from approx. 7000 in 2000 to over 11,000 in 2015. The NRCC includes 4020 patients with hemophilia A and 859 patients with hemophilia B. The prevalence of the rare type 3 vWD is 0.20/100,000 inhabitants. Less common congenital bleeding disorders include the following deficiencies: Factor I (fibrinogen), Factor II (prothrombin), Factor V, Factor VII, Factor X, Factor XI and Factor XIII, which affect 1953 patients. Hepatitis C Virus (HCV) infection affects 1561 patients, more than 200 of whom have two infections (HCV + HIV). Estimated hemophilia-related drug consumption in 2015 was approx. 550 million IU of FVIII for hemophilia A patients and approx. 70 million IU of FIX for hemophilia B patients. The NRCC, with its bleeding disorder data set, is a tool that can provide answers to fundamental questions in public health, monitoring care provision and drug treatment, as well as facilitating clinical and epidemiological research.

The first data from the haemovigilance system in Italy.

BACKGROUND: Haemovigilance is defined as the surveillance of adverse reactions occurring in donors and in recipients of blood components and as epidemiological surveillance of donors. The ultimate purpose of haemovigilance is to prevent the repetition of adverse events and reactions. Since the 2002/98/EC Directive came into force, the introduction of haemovigilance systems has become a priority for all countries in the European Community. The Italian haemovigilance system is essentially in line with the Directive, although it does not include surveillance of adverse events in donors and does not have a national level of registration of severe incidents connected with the collection, processing and storage of blood and blood components. Epidemiological surveillance of donors has been performed nationally since 1989 for HIV and since 1999 for HBV, HCV and Treponema pallidum. Surveillance of adverse events in recipients was started at the end of 2004. MATERIALS AND METHODS: The national form proposed for notifying adverse reactions (PETRA) was prepared by the National Institute of Health and distributed to all Transfusion Structures. RESULTS: The data collected (adverse reactions, errors, and near miss errors) came from 21.0% of the Transfusion Structures in 2004 and 38.4% in 2005. The system monitored 49.6 % of all the units distributed in Italy. Overall 1,495 adverse reactions were reported, which is equivalent to 0.8 reactions/1,000 units of blood components distributed. There were 16 reports of errors involving transfusions to the wrong patient. Not all the Transfusion Structures sent their data using the PETRA form. From the 986 PETRA forms received, it was possible to analyse the relevance of the transfusion, the outcome of the patient, the type of blood component involved, the type of error and the type of near miss error. CONCLUSIONS: This study is the first Italian report on transfusion errors and adverse reactions.