Search

Aupres du Service de Transfusion de Ragusa a ete realise un suivi statistique de la procedure de filtration en ligne pour demontrer que le changement de la methodologie, comme l’Introduction du nouveau systeme de filtration COMPOFLOW SELECT CQ31555, a donne les resultats attendus. Soixante-quinze hematies filtrees pre-storage ont ete soumises a un controle. Pour chaque unite on a enregistre les poids des hematies concentrees, les valeurs de Hb, HCT, nombre de leucocytes residus. Pour mesurer l’efficacite d’un procede de production sont utilises les indices de capacites: l’indice Cp et le Cpk. Pour le HCT le Cpk = (2.519; 2.638) resulte majeur de 1, l’ampleur des donnees se situe dans les limites de tolerance indiquant une tres bonne capacite de la procedure. L’indice Cp est 2.579 etant donne que Cpk et Cp sont deux valeurs similaires cela suppose une situation ou la moyenne est centree sur le point median des specifications. Meme situation pour le volume des unites Cpk = (1.577; 1.18), Cp = 1.37. Pour les leucocytes residus l’indice Cpk = (8.189; 0.34). Choisissant la plus petite des deux valeurs calculees c’est-a-dire comprise entre 0 et 1, cela indique qu’une partie des unites de la procedure depassent les limites. Ce probleme a ete attribue a une basse performance du filtre d’une seule unite. L’indice Cpk de l’hemoglobine est egal a (1.27;2.02), les deux resultats resultent majeurs de 1, cela indique que la procedure est sous controle. A partir des analyses de la capacite nous avons deduit que la procedure satisfait les limites des specifications superieures et inferieures preetablies en phase de validation, permettant de tenir sous controle les eventuelles causes source d’erreur.

Les transfusions a domicile necessitent une gestion specifique, y compris la gestion des complications des transfusions. A considerer les conditions preexistantes du patient, l’incidence et la gravite des reactions, nous utilisons un questionnaire. Les Medecins Generalistes (MG) adressent leur demande au personnel du service immuno-hematologie de l’Hopital qui en evalue la pertinence et transmet les composants sanguins a notre Medecin affilie. Les transfusions effectuees utilisent le meme systeme biometrique (SecurBlood) utilise a l’hopital. En 2018, nous avons transfuse 1134 patients en consultation externe a Raguse. Sur les 2150 produits sanguins transfuses (97 % de globules rouges, 3 % de plaquettes), 13 (0,6 %) reactions ont ete repertoriees : 2 etaient sans gravite et ont ete resolues en quelques minutes ; 11 ont requis une intervention therapeutique. Neuf patients souffraient d’hypertension et de dyspnee preexistante et ont manifeste une surcharge volumique liee a la transfusion (7), une dyspnee (1), et une reaction transfusionnelle febrile non hemolytique (1). La transfusion a ete interrompue. Seuls 2 patients presentant une insuffisance renale legere et une fibrillation auriculaire preexistantes ont du etre hospitalises : ils souffraient d’un œdeme pulmonaire et de surcharge volumique. Aucun patient n’avait recu de premedication. L’utilisation d’un questionnaire durant la transfusion nous permet de collecter les symptomes cliniques et les conditions preexistantes pouvant conduire aux reactions transfusionnelles. Les MG pourraient l’utiliser avant transfusion pour identifier les patients qui devraient beneficier d’une premedication ou etre transfuses en milieu hospitalier.

L’etablissement du Service de Transfusion Sanguine (ST) de Raguse est le siege, depuis 1998, d’un des quatre Centres de Don de Moelle Osseuse de la Region Sicile. Des medecins recruteurs du ST selectionnent les donneurs potentiels, tandis que le typage HLA est effectue dans le laboratoire HLA annexe, accredite EFI. Cette etude expose l’activite du Centre de Dons de Raguse pendant la periode 1998–2018. Dans ce but, les donnees relatives au numero de Donneurs de Moelle Osseuse actifs et ecartes, classes par sexe, âge, ethnie, preference de type de don (de sang medullaire ou de sang peripherique), resolution allelique HLA et rappel des donneurs pour verifier une eventuelle compatibilite avec un receveur, ont ete extrapolees du Logiciel de Gestion du Registre Italien des Donneurs de Moelle Osseuse (IBMDR). Au vu des donnees obtenues, resumees dans la Tableau 1 , il est possible de tirer les conclusions suivantes : grâce a l’activite de selection, qui a considerablement augmente ces dernieres annees, 63 % de nos donneurs ont moins de 35 ans (1278 sur 2020), ce qui permet de prevoir une permanence d’au moins 20 ans dans le Registre. Grâce au recrutement recent, et grâce aussi au programme de requalification des donneurs finance par IBMDR, l’ensemble des donneurs resulte avoir un typage de haute resolution selon les standards actuels dans 77 % des cas (1564 sur 2020), raison pour laquelle il ressort que la possibilite de rappeler des donneurs de moelle osseuse pour le don proprement dit est proportionnellement elevee. En effet, sur 12 work up (c’est-a-dire dons effectifs de cellules souches) que nous avons geres au total, 2 ont ete effectues en 2017 et 3 en 2018.

Dans les 12 etablissements AVIS que compte la Province de Raguse nous avons applique, conformement au principe de “don personnalise” deja introduit par Bonomo et coll. (2004), des criteres de selection ( Tableau 1 ) selon lesquels on conseille a chaque donneur le type de don le plus indique pour lui. En 2018, 25 270 donneurs ont ainsi ete selectionnes. On a ainsi collecte 39,933 unites dont : 27,435 (68,70 %) SI, 9,360 (23,44 %) P, 1,846 P-PLT (4,62 %), 835 R-P (2,1 %). Nous avons obtenu 2,681 unites grâce a des systemes d’apherese multi composants. Pendant la meme annee, 2,947 donneurs potentiels ont ete examines afin de rechercher d’eventuels cas de porteurs d’hemoglobinopathie ou de trait thalassemique. Parmi eux, 183 (6,2 %) resultent etre porteurs de trait thalassemique, 35 (1,2 %) de HbS, 3 (0,1 %) de HbC et 6 (0,2 %) d’autres pathologies de l’hemoglobine. Les porteurs d’hemoglobinopathie S ou C ont ete exclus de la liste des donneurs. Il a ete conseille de donner plasma et plaquettes aux femmes en âge fertile et aux donneurs presentant de faibles valeurs de Hb ou le trait thalassemique afin de preserver leur sante. Nous avons obtenu des autres donneurs des unites SI qui respectent des standards de qualite eleves en ce qui concerne les taux de Hb et Hct. 6,7 % des unites collectees en 2018 derivent de systemes d’apherese multi composants dont il est necessaire que les centres de collecte soient dotes, ainsi que d’un personnel dument forme a leur utilisation ( Tableau 1 ).

Background We analysed the relationship between baseline haemoglobin levels and the need for post-operative blood transfusion in our patients. The aim of this study was to evaluate and optimize the pre-operative autologous blood donation (PABD) program at our hospital through a constant audit. Materials and methods Between January 1997 and December 2006 we evaluated 1198 consecutive patients who underwent elective, unilateral, primary total hip or knee arthroplasty and who met our inclusion criteria. We determined the baseline haemoglobin level to establish the relationship to the need for post-operative transfusion. Results The results of our study show that the baseline haemoglobin level is a strong predictor of blood transfusion after unilateral, primary total hip or knee arthroplasty. Conclusions The baseline haemoglobin level is a strong predictor of blood transfusion after elective, unilateral, primary total hip or knee arthroplasty. On the basis of these findings, we do not recommend autologous predonation for patients with a baseline haemoglobin level of >14 g/dl moreover we always recommend the use of a blood cell salvage system and a constant audit of pre-operative autologous blood donation (PABD) to avoid unnecessary expense and waste.

The treatment of thalassemia is still essentially based on continuous transfusion supporting using red cell concentrates (RCC) prepared in different ways. For patients with sickle-cell disorders, either urgent or chronic red blood cell transfusion therapy, is widely used in the management of sickle cell disease (SCD) because it reduces HbS level and generally prevents recurrent vaso-occlusive disease (VOD). Recently, the introduction of pre-storage filtration to remove leukocytes and the use of techniques for multicomponent donation have increased the types of blood components available for transfusion purposes. The clinical effects of different types of blood components in thalassaemic and sickle-cell patients have not been extensively studied so far. We evaluated the impact of the various different blood components currently available on transfusion needs, transfusion intervals and adverse reactions in order to determine which is the most advantageous for transfusion-dependent thalassaemic and sickle-cell patients followed in our centre. We believe that the optimal characteristics of the RCC are aged less than 10 days from time of collection; Hb content greater than 56 g per unit; Hct: 55-60%; volume (including additive) 300 mL+/-20%; leucodepleted to less than 200,000 leukocytes per unit; low cytokine content (achievable by pre-storage filtration carried out between two and 24 hours after the collection); lack of microaggregates (achievable by pre-storage filtration or filtration in the laboratory) and protein content less than 0.5 g per unit for patients allergic to plasma proteins (achievable with manual or automated washing). It is still recommended that the blood transfused should be as fresh as possible, compatible with the centre's product availability and the centre's organisation should be continuously adapted to this aim. We always transfuse blood within 10 days of its collection, respecting Rh and Kell system phenotypes. Pre-storage filtration is strongly recommended, both in order to prevent adverse reactions through the marked leucodepletion (less than 200,000 leukocytes per unit) and for a better standardisation of the final product, including the certainty that the product does not contain clots, an assurance that bed-side filtration cannot give. The RCC should be produced using a method causing as little as possible stress to the red cell membrane. The use of RCC with a high content of Hb (less than 56 g per unit) is strongly recommended, because our study clearly shows that this reduces the number of exposures to donors and the number of accesses to hospital, thus improving the patient's quality of life.

The use of cell separators in multicomponent collection (MCC) makes it possible to use donors effectively by personalising the donation on the basis of their haemotological and physical profiles and thereby standardising the product. We have applied the selection parameters currently used in our collection centre to 6687 donors using a common software programme for all: 57.6% were eligible for the various forms of MCC, although our parameters are even stricter than those required by law. Between 01 September 2001 and 28 February 2002, 345 MCC (9% of all the donations made) were performed and assessed: 111 donations of double red cell units, 153 donations of red cells and plasma, 62 donations of plasma and platelets, 19 donations of double platelet units: only slight, adverse reactions were encountered in 6% of the procedures. 68 double red cell unit donors and 65 red cell and plasma donors were then reassessed 6 months after MCC: the parameters assessed (hemoglobin, serum iron, ferritin, and total protein) were the same as the pre-donation data. All the units collected complied with legal requirements. With the use of parameters based on donor hematological and physical characteristics we can move from the concept of tailored transfusions to the concept of tailored donations thereby ensuring donor safety and meeting patient needs.

Background: the Registro Italiano Trombocitemie (RIT) was activated mainly to evaluate the diagnosis and therapy appropriateness in the thrombocythemic patients with Ph-negative myeloproliferative neoplasm (MPN) observed in the adhering centers. Objective: to evaluate how the diagnostic and therapeutic approach changed in the RIT patients diagnosed with thrombocythemic MPN in the last two decades. Methods: the RIT centers registered by a web-based system during the years 2005-2014 their thrombocythemic MPN patients, and semesterly updated their follow-up data. For patients diagnosed before 2005, the data on diagnosis and prior follow-up were retrospectively collected. The diagnostic process and the initial treatment (started into the first year after diagnosis) were comparatively analyzed in the patients diagnosed before and after 2005. Results: the RIT centers registered 2629 patients. 2388 of them, object of this analysis, were diagnosed between1995 and 2014: 1098 (46%) in the decade 1995-2004 (Group I), and 1290 (54%) in the decade 2005-2014 (Group II). The diagnostic process in the patients of Group II and Group I included bone marrow biopsy (BMB, performed into 1 year and before any cytoreduction): 85% vs 80%, p The patients of Group II, as compared with those of Group I, showed a similar gender distribution (M/F ratio 0.61 vs 0.65, p 0.452), and had at diagnosis: a higher age (median 60 vs 57 years, p 60 years in 50% vs 45% of cases, p Moreover, they had: a lower platelet (PLT) count (median 737 vs 775 x 109/L, p 10 x 109/L in 28% vs 26% cases); a similar median levels of hematocrit (HCT %, in females 41.4 vs 41.0; in males 44.7 vs 44.6) and hemoglobin (Hb g/dL, in females 13.8 vs 13.6; in males 15.0 vs 14.9). The BMB, revised according to the WHO 2008 criteria, showed a not different distribution (p 0.21) of ET (64% vs 61%), ep-PMF (16% vs 17%), PMF (3% vs 2%), PV (4% vs 4%), and U-MPN (13% vs 16%. The JAK2 V617F mutation in patients of Group II (at diagnosis) and of Group I (after diagnosis) was found in 62% and in 58% of tested cases (p 0.054), respectively. The patients at high standard thrombotic risk were 58% vs 52%, p 0.004. In the patients of Group II and Group I the distribution of the treatment started into the first year was significantly different (p The treatment CYT ± AntiPLT was started in the patients at high standard thrombotic risk with a rate of 81% vs 80%, respectively, and in the patients at low standard thrombotic risk in 37% vs 43% of cases, respectively. The initial treatment CYT±AntiPLT was related, in multivariate analysis, both in patients of Group II and Group I, with older age (>60 and 40-60 vs 1000 and 700-1000 vs Conclusion: in the studied thrombocythemic MPN patients the real-life diagnostic approach was improved after 2005 not only due to the routine use of JAK2 tests, but also due to the higher rate of BMB done (85% vs 80%). The appropriateness of the cytoreductive treatment (CYT±AntiPLT started into one year from diagnosis) remained high in patients at high standard thrombotic risk (over 80% of cases were treated). Concomitantly, the inappropriate use of the cytoreductive drugs in patients at low standard thrombotic risk appreciably decreased (from 43% to 37% of cases). Moreover, it has to be remarked that the therapeutic approach was significantly influenced not only by older age and prior thrombosis, but also by thrombocytosis (PLT count >700 x 109/L), disease-related symptoms, and inconstantly by leukocytosis and CVRFs. Table Table. Disclosures Gugliotta: SHIRE Co.: Honoraria. Gugliotta:Bristol Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria.

Blood and apheresis donations are widely considered to be safe with a low incidence of adverse reactions and injuries; however, data reported in the medical literature on the prevalence of adverse events in donors and studies on the predictive risk factors for donor reactions are limited and contradictory.From January 2002 to December 2006 we recorded every adverse reaction verified during 240,596 consecutive blood and apheresis donations (183,855 homologous whole blood donations, 6,669 autologous whole blood donations, 38,647 plasmapheresis, 2,641 plateletpheresis and 8,784 multicomponent donations) at the Italian Transfusion Centres of Verona and Ragusa,.Using a special, pre-arranged form within the quality system, a total of 686 adverse reactions (related to 0.28% of all donations) were recorded. Vasovagal reactions, mostly of mild intensity, were the most commonly observed adverse reactions, with a frequency of 0.20% (487/ 240,596). The frequency of the vasovagal reactions varied according to the different types of donation, being 0.19% (346/183,855) for homologous whole blood donations, 0.24% (16/6,669) for autologous whole blood donations, 0.16% (63/38,647) for plasmapheresis, 0.68% (18/2,641) for plateletpheresis and 0.49 (43/8,784) for multicomponent donations. Citrate toxicity was reported in 0.38% (189/50,072) of apheresis donations. Severe adverse reactions were very rare, as they occurred in 0.004% of the donations (10/240,596).In conclusion, the results of our 5-year survey document that apheresis and blood donation are safe procedures for the donor with a low incidence of adverse reactions; the adverse reactions that did occur were mostly mild and resolved rapidly.

One of the most serious risks of blood transfusions is an error in ABO blood group compatibility, which can cause a haemolytic transfusion reaction and, in the most severe cases, the death of the patient. The frequency and type of errors observed suggest that these are inevitable, in that mistakes are inherent to human nature, unless significant changes, including the use of computerised instruments, are made to procedures.In order to identify patients who are candidates for the transfusion of blood components and to guarantee the traceability of the transfusion, the Securblood system (BBS srl) was introduced. This system records the various stages of the transfusion process, the health care workers involved and any immediate transfusion reactions. The patients and staff are identified by fingerprinting or a bar code. The system was implemented within Ragusa hospital in 16 operative units (ordinary wards, day hospital, operating theatres).In the period from August 2007 to July 2008, 7282 blood components were transfused within the hospital, of which 5606 (77%) using the Securblood system. Overall, 1777 patients were transfused. In this year of experience, no transfusion errors were recorded and each blood component was transfused to the right patient. We recorded 33 blocks of the terminals (involving 0.6% of the transfused blood components) which required the intervention of staff from the Service of Immunohaematology and Transfusion Medicine (SIMT). Most of the blocks were due to procedural errors.The Securblood system guarantees complete traceability of the transfusion process outside the SIMT and eliminates the possibility of mistaken identification of patients or blood components. The use of fingerprinting to identify health care staff (nurses and doctors) and patients obliges the staff to carry out the identification procedures directly in the presence of the patient and guarantees the presence of the doctor at the start of the transfusion.

The aim of this study was to compare the routine use of two automated systems (OrthoAutoVue Innova, microcolumn, and Immucor Galileo, solid phase) for the screening and identification of irregular red blood cell alloantibodies in samples, analysed in our Transfusion Service during 6 months of normal activity. The study focused particularly on an evaluation of the repeatability of the screening tests, the identification of antibody specificities and the identification of antibodies in samples showing discordant results.Overall 2,229 samples from potential blood donors (A), multiply transfused patients with blood disorders (DH), potential transfusion recipients (TS), and external cases (E) were studied. The protocols were carried out according to the manufacturers recommendations.The screening tests detected 78 samples that were positive with both systems, while 18 were positive only with Immucor and 11 only with Ortho (thus, overall, Immucor detected 96 positive samples and Ortho 89 positive samples). The use of the respective identification panels enabled us to identify the antibodies in 65 samples with Immucor and in 61 samples with the Ortho system; 74 antibodies were identified with Immucor (55 with a single specificity and 19 with mixed specificities) and 68 antibodies with Ortho (51 and 17, respectively). In the remaining cases (31 samples for Immucor and 28 for Ortho), the antibody specificity was not identified. The two systems were found to be essentially similar. The Immucor system revealed a greater number of antibodies, mainly because of its greater sensitivity at detecting anti-D antibodies.Both systems showed a repeatability of over 85%, demonstrating that automation of immunohaematological tests is advantageous. The specificity of the antibody was identified in 68% of the samples. Furthermore, using the two systems led to the identification of ten new antibodies (6 anti-D, 2 anti-E, 1 anti Le(a), and 1 anti-Vel), which would not have been detected had only one of the two methods been used.

We tracked the results of 394 manual or automatic red blood cell exchanges done with a cell separator in 20 sickle cell patients at high risk for recurrent complications. Over an average of 6 years, none of the patients developed complications related to the procedure or to the increased blood use. It was safe and effective in preventing complications of sickle cell disease, and if done automatically, reduced iron overload. Ferritin levels also decreased in patients treated with automatic red blood cell exchange. Furthermore, using Single Donor Red Blood Cell units (SDRC) we reduced the potential exposure to transfusion transmitted infectious diseases (TTI).

The hepatic peptide hepcidin is the key regulator of iron metabolism in mammals. Recent evidence indicates that certain forms of hereditary hemochromatosis are caused by hepcidin deficiency. Juvenile hemochromatosis is associated with hepcidin or hemojuvelin mutations, and these patients have low or absent urinary hepcidin. Patients with C282Y HFE hemochromatosis also have inappropriately low hepcidin levels for the degree of iron loading. The relationship between the hemochromatosis due to transferrin receptor 2 (TFR2) mutations and hepcidin was unknown. We measured urinary hepcidin levels in 10 patients homozygous for TFR2 mutations, all with increased transferrin saturation. Urinary hepcidin was low or undetectable in 8 of 10 cases irrespective of the previous phlebotomy treatments. The only 2 cases with normal hepcidin values had concomitant inflammatory conditions. Our data indicate that TFR2 is a modulator of hepcidin production in response to iron. (Blood. 2005;105:1803-1806)

The aim of this study was to analyze the role of HFE mutations in blood donors with iron parameters suggesting iron overload, taking into account the regional distribution of HFE mutations in Italy. We studied 5880 subjects undergoing evaluation for blood donation eligibility, from different areas of Italy. Abnormal iron parameters were defined as transferrin saturation (TS) 450% or 445% and serum ferritin (SF) 4300 or 4250mg/ml in males and females, respectively. Subjects with increased TS and/or SF were re-tested and typed for HFE mutations C282Y and H63D. A total of 548 individuals had increased iron parameters at first testing. In total, 179/548 were available for retesting, and in 109 increased TS and/or SF were confirmed. Increased TS was confirmed in 25 individuals, among whom three were C282Y homozygotes and six were compound heterozygotes for C282Y and H63D. Increased TS was more frequent in northern Italy than in southern regions. In individuals with increased TS and/ or SF, the frequency of C282Y and H63D was 0.13 and 0.21 in northern-Italy versus 0.05 and 0.45 in southern Italy (P ¼ 0.004 for H63D). Nine out of 10 individuals carrying hemochromatosis-associated genotypes (including compound heterozygosity for C282Y and H63D) originated from northern regions. Among controls, the allelic frequencies of C282Y and H63D were 0.037 and 0.16 in the northern regions and 0.015 and 0.16 in the southern regions. In conclusion, over one-third of individuals with persistently altered TS carried hemochromatosisassociated genotypes, confirming that a diagnostic approach based on TS and genotyping of selected cases may represent a viable screening procedure. The Hematology Journal (2003) 4, 436–440. doi:10.1038/sj.thj.6200324

Deferiprone has been suggested as an effective oral chelation therapy for thalassemia major. To assess its clinical efficacy, we compared deferiprone with deferoxamine in a large multicenter randomized clinical trial. One-hundred forty-four consecutive patients with thalassemia major and serum ferritin between 1500 and 3000 ng/ml were randomly assigned to deferiprone (75 mg/kg/day) (n = 71) or deferoxamine (50 mg/kg/day) (n = 73) for 1 year. The main measure of efficacy was the reduction of serum ferritin. Liver and heart iron contents were assessed by magnetic resonance. Liver iron content and fibrosis stage variations were assessed on liver biopsy by the Ishak score in all patients willing to undergo liver biopsy before and after treatment. The mean serum ferritin reduction was 222 +/- 783 ng/ml in the deferiprone and 232 +/- 619 ng/ml in the deferoxamine group (P = 0.81). No difference in the reduction of liver and heart iron content was found by magnetic resonance between the two groups. Thirty-six patients accepted to undergo repeat liver biopsy: 21 in the deferiprone and 15 in the deferoxamine group. Their mean reduction of liver iron content was 1022 +/- 3511 microg/g of dry liver and 350 +/- 524, respectively (P = 0.4). No difference in variation of the Ishak fibrosis stage was observed between the two groups. Treatment was discontinued because of reversible side effects in 5 patients in the deferiprone group (3 hypertransamin/asemia and 2 leukocytopenia) and in none in the deferoxamine group. These findings suggest that deferiprone may be as effective as deferoxamine in the treatment of thalassemia major with few mild and reversible side effects.

Hereditary hemochromatosis usually results from C282Y homozygosity in the HFE gene on chromosome 6p. Recently, a new type of hemochromatosis (HFE3) has been characterized in 2 unrelated Italian families with a disorder linked to 7q. Patients with HFE3 have transferrin receptor 2 (TFR2) inactivated by a homozygous nonsense mutation (Y250X). Here the identification of 2 newTFR2 mutations is reported. In a large inbred family from Campania, a frameshift mutation (84-88 insC) in exon 2 that causes a premature stop codon (E60X) is identified. In a single patient with nonfamilial hemochromatosis, a T→A transversion (T515A), which causes a Methionine→Lysine substitution at position 172 of the protein (M172K), has been characterized. TFR2 gene gives origin to 2 alternatively spliced transcripts—the α-transcript, which may encode a transmembrane protein, and the β-transcript, a shorter, possibly intracellular variant. Based on their positions, the effects of the identified mutations on the 2 TFR2 forms are expected to differ. Y250X inactivates both transcripts, whereas E60X inactivates only the α-form. M172K has a complex effect: it causes a missense in the α-form, but it may also prevent the β-form production because it affects its putative initiation codon. Analysis of the clinical phenotype of 13 HFE3 homozygotes characterized at the molecular level has shown a variable severity, from nonexpressing patients to severe clinical complications. The identification of new mutations of TFR2 confirms that this gene is associated with iron overload and offers a tool for molecular diagnosis in patients without HFE mutations.

Haemochromatosis is a common recessive disorder characterized by progressive iron overload, which may lead to severe clinical complications. Most patients are homozygous for the C282Y mutation in HFE on 6p (refs 1–5). A locus for juvenile haemochromatosis6 (HFE2) maps to 1q (ref. 7). Here we report a new locus (HFE3) on 7q22 and show that a homozygous nonsense mutation in the gene encoding transferrin receptor-2 (TFR2) is found in people with haemochromatosis that maps to HFE3.

Hemochromatosis (HH) is usually caused by the homozygous state for C282Y mutation in the HFE gene. A minority of iron loaded patients have no mutations in this gene. An infrequent subset shows an early-onset aggressive disorder, denoted juvenile hemochromatosis (JH), which has no linkage to 6p. In this report we describe six patients from three unrelated Italian families, four men and two women, aged 21 to 44 with the typical hemochromatosis phenotype, who are homozygous for the wild type allele at the HFE gene. In two families the disorder is unlinked to 6p; in one family some features of the juvenile form are seen, but linkage to 6p is not excluded. Our results point to genetic forms of hemochromatosis not associated with HFE and raise the problem of whether non-HFE hemochromatosis in Italy is related to the "juvenile" form. They also emphasize the importance of phenotypic as well as genetic diagnosis of HH.

For patients with severe SCD not eligible for hydroxyurea, two major therapeutic options are currently available: blood transfusion, and bone marrow transplantation. Either urgent or chronic red blood cell transfusion therapy, is widely used in the management of SCD but determines a progressive increase of ferritin level and is also limited by the development of antibodies to red cell antigens. The introduction of chronic red blood cell exchange and prestorage filtration to remove leucocytes and the use of techniques for multicomponent donation could be a good solutions. Thus, the aims of our studies were to evaluate the clinical effects of the different blood components in terms of annual transfusion needs and the intervals between transfusion, moreover we evaluated the efficacy of chronic red blood cell exchange (manual or automatic with cell separator) in preventing SCD complications and limiting iron overload. In our center we follow 78 patients affected by Sickle Cell Disease. We selected 36 patients occasionally treated with urgent red blood cell exchange because they had less than 2 complications/Year, and 42 patients regularly treated with chronic red blood cell exchange because they had more than 2 complications/Year with Hospital Admission. Moreover among these we selected 10 patients for fulfilling the criteria of continuous treatment at the Centre for at least 48 months with no interruptions, even sporadic and absolute transfusion dependency. All 10 patients were evaluated for a period of 4 years, during which two different systems of producing RCC were used. In the second two the patients were transfused with RCC obtained from filtering whole blood prestorage or with RCC from apheresis filtered prestorage. These products differed from those used in the preceding two years, during which the leucodepletion was obtained by bed-side filtration For all the patients we performed 782 automatic red blood cell exchanges and 4421 units of RCC were transfused. The exchange procedures were extremely well-tolerated by the patients and adverse effects were limited to symptoms of hypocalcaemia during automatic red blood cell exchange with cell separator. After every red blood cell exchange we obtained HbS level < 30%. The10 patients selected received respectively a mean of 6.9 and 6.1 units of RBCs exchanged per automatic procedure, in the first two years and in the second two years. Alloantibody developed in 14 patients but only 2 clinically significant and about the observed frequency of transfusion reactions it was very low. All patients treated with chronic red blood cell exchange had an improvement of the quality of life with a reduced number of complications/year (