Patient blood management knowledge and practice among clinicians from seven European university hospitals: a multicentre survey.

BACKGROUND AND OBJECTIVES: The aim of this survey was to evaluate the knowledge about Patient Blood Management (PBM) principles and practices amongst clinicians working in seven European hospitals participating in a European Blood Alliance (EBA) project. MATERIALS AND METHODS: A web-based questionnaire was sent to 4952 clinicians working in medical, surgery and anaesthesiology disciplines. The responses were analysed, and the overall results as well as a comparison between hospitals are presented. RESULTS: A total of 788 responses (16%) were obtained. About 24% of respondents were not aware of a correlation between preoperative anaemia (POA) and perioperative morbidity and mortality. For 22%, treatment of POA was unlikely to favourably influence morbidity and mortality even before surgery with expected blood loss. More than half of clinicians did not routinely treat POA. 29%, when asked which is the best way to treat deficiency anaemia preoperatively, answered that they did not have sufficient knowledge and 5% chose to 'do nothing'. Amongst those who treated POA, 38% proposed red cell transfusion prior to surgery as treatment. Restrictive haemoglobin triggers for red blood cell transfusion, single unit policy and reduction of number and volumes of blood samples for diagnostic purposes were only marginally implemented. CONCLUSION: Overall, the responses indicated poor knowledge about PBM. Processes to diagnose and treat POA were not generally and homogeneously implemented. This survey should provide further impetus to implement programmes to improve knowledge and practice of PBM.

Role of non-HLA genetic polymorphisms in graft-versus-host disease after haematopoietic stem cell transplantation.

Graft-versus-host disease (GvHD) is the main complication after haematopoietic stem cells transplantation (HSCT) and acute forms (aGvHD) occur in 20-40% of cases even after donor (D) and recipient (R) HLA matching, apparently because of D/R minor histocompatibility antigen (mHA) mismatches and cytokine polymorphisms. The genotype of cytokines and mHA of 77 haematological R following HSCT from HLA identical siblings were determined to detect genetic polymorphisms correlated with GvHD. We analysed TNFA (-863 C/A, -857 C/T and G/A at positions -574, -376, -308, -244, -238), IL-10 (-1082 G/A, -819 C/A, -592 C/T), IL-1B (T/C +3953), IL-1RA (VNTR), HA-1 (H/R allele) and CD-31 (C/G at codon 125, A/G at codon 563). Allele frequencies were in Hardy-Weinberg equilibrium and similar to those of 77 healthy controls. We observed positive correlations between a lower risk of clinically significant aGvHD and both the presence of -1082G -819C -592C IL-10 haplotype when both R and D are considered together and the absence of R IL-1RA allele 2. Furthermore, we observed an association between the absence of TNF-A -238 A allele and the risk of extensive chronic GvHD. mHA and cytokines genotyping would thus seem a valid source of information for the prior identification of recipients with a higher risk of aGvHD.

Coeliac disease associated with Sjögren's syndrome, renal tubular acidosis, primary biliary cirrhosis and autoimmune hyperthyroidism.

Although coeliac disease may occur in patients affected by another immune-mediated disorder, its coexistence with multiple autoimmune diseases is not frequently described. We report here the case of a 45-year-old woman referred to our centre because of diarrhoea and weight loss, who had already received a diagnosis of primary biliary cirrhosis, Sjögren's syndrome and renal tubular acidosis. Following the development of diarrhoea we established the diagnosis of coeliac disease, based on the presence of anti-endomysium antibodies and a compatible duodenal biopsy. Despite gluten withdrawal she went on to develop an autoimmune hyperthyroidism. The patient tested positive for HLA DRB1*03 and DQB1*02. The association is unlikely to be casual and may be explained by autoimmune mechanisms, genetic susceptibility and favouring environmental factors commonly shared by the diseases of our patient.

Identification of a new HLA-DRB1 allele in three members of an Italian family.

Abstract A new human leucocyte antigen (HLA)-DRB1 allele, HLA-DRB1*1149, has been identified in three members of an Italian family during routine sequence based typing. This new allele differs from HLA-DRB1*110101 only for a single nucleotide substitution at position 113 of exon 2 resulting in an amino acid change from Valine (GTG) to Alanine (GCG) at codon 38.

Pregnancy in heart transplant recipients.

The aim of this report is to present data from Italian cardiac transplant centers assessing pregnancy after cardiac transplantation. Our retrospective survey included 10 pregnancies occurring in 7 patients during January 1991 to February 2002. Eight pregnancies were completed successfully and 2 abortions were reported (frequency rate 20%). No complications were observed during pregnancy or after delivery. Of 8 infants studied, 6 (75%) were born at term and 2 (25%) pre-term. One baby presented congenital talipes valgus. Pediatric development was uneventful. The data from the literature and our series show that a multidisciplinary approach is mandatory. The course of pregnancy is usually normal and the maternal and fetal outcomes are usually favorable. Although no fetal malformations have been reported, prolonged follow-up of these infants is required.

New HLA-A*11 allele, A*1112, identified by sequence-based typing.

In this report, we describe the identification of HLA-A*1112, a novel HLA-A*11 allele found in two Italian families. The new allele was detected during routine HLA typing by a polymerase chain reaction sequence-specific primer and was confirmed by high-resolution sequencing-based typing. The nucleotide sequences of HLA-A*1112 exons 2 and 3 are identical to HLA-A*11011 except for a single nucleotide substitution in codon 90 (GAC-->GCC).

[Pregnancy after kidney transplantation. Review of the international literature and presentation of personal case reports]. / Gravidanza dopo trapianto di rene. Revisione della letteratura internazionale e presentazione della casistica personale.

BACKGROUND: Advances in surgical techniques and immunosuppression have improved the results in organ transplantation. The quality of life in these patients is good in the most of cases and pregnancy, which means for them to resume a normal life, isn't an exceptional event, specially for kidney transplant recipients. METHODS: Retrospective data regarding pregnancies observed at the Dept. of Nephrology and Dialysis of the S. Giovanni Battista Hospital in Turin, have been collected to value the pregnancy frequency and outcome (complications, miscarriage, therapeutic abortion), the mother follow-up as a function of transplant rejection risk, the newborn conditions, their hematological and immunological situation, and the children follow-up. RESULTS: This study includes 9 pregnancy (6 at term and 3 abortions), observed since 1987 in 6 kidney transplant recipients. Congenital malformations or immunological diseases have not been observed; according to the literature, there was a high frequency of preterm delivery and intrauterine grow retardation. Complications during pregnancy were observed in 5 cases (83.3%). CONCLUSIONS: The study confirms that kidney transplant recipients can carry a pregnancy through and give birth to healthy infants, but these pregnancies are to be regarded as being at high risk and require a multi-disciplinary approach.

Cytotoxic T lymphocyte precursor frequency as a predictor of acute graft-versus-host disease in bone marrow transplantation from HLA-identical siblings.

The measurement of precursor frequencies of donor anti-recipient cytotoxic T lymphocytes (CTL-p) has been shown to predict the incidence and the severity of acute graft-versus-host disease (aGVHD) in unrelated donor bone marrow transplantation (BMT). In HLA-identical sibling BMT, where aGVHD is most likely caused by minor histocompatibility antigen mismatches, this assay did not appear to be sensitive enough to provide similar predictive information. In this study, the CTL-p frequencies and the incidence and severity of aGVHD in 51 onco-hematological patients transplanted from HLA-identical siblings were compared. Sibling donors were selected on the basis of HLA identity using serological typing for HLA-A, B, C antigens, whereas HLA-DRB was tested by molecular analysis. Sibling identity was also confirmed by DNA heteroduplex analyses. Fifteen out of 21 (71%) patients with high precursor frequency (>1:100 x 10(3)) and 12 out of 30 (40%) with low precursor frequency (<1:100 x 10(3)) experienced clinically significant (II-IV) aGVHD. A significant correlation (P = 0.04) between CTL-p frequency and severe aGVHD was demonstrated. Moreover there was a positive trend for a high frequency response according to an increasing grade of aGVHD, which was statistically significant (P = 0.04). In our experience the CTL-p assay is a helpful predictive test for aGVHD in HLA-identical sibling BMT, indicating high risk patients possibly requiring additional prophylaxis.

Analysis of the turin umbilical cord blood bank registry.

BACKGROUND: The polymorphic nature of the HLA system reduces a patient's probability of finding an HLA-compatible unrelated bone marrow (BM) donor, even though more than 6 million individuals are enrolled in international registries. Recently, umbilical cord blood (UCB) has been successfully employed as a source of HPCs. The use of such cells reduces the risk of GVHD and allows transplants with one or two HLA mismatches. UCB represents an expensive resource: therefore, it is necessary to carefully manage the UCB unit inventory. STUDY DESIGN AND METHODS: The current study analyzed the genetic heterogeneity of HLA-A, -B, and -DR gene frequencies between pools of UCB and unrelated-donor BM in the Piedmont (an administrative region of Italy). An Italian hematology patient's probability of finding complete or partial matches as a function of donor pool size was determined by considering subsamples randomly selected from the local unrelated BM donors. RESULTS: The HLA gene frequencies in UCB and unrelated-donor BM pools were not significantly different. The search simulation, based on actual HLA phenotypes, showed that the percentage of Italian patients matched with an HPC unit increases remarkably if 1 or 2 mismatches are accepted, reaching a proportion of 90 percent with an inventory of only about 500 units, while the increment is not so remarkable if the number of UCB units is greater. CONCLUSION: To optimize economic resources and to be internationally competitive, UCB banks should aim to increase the genetic heterogeneity of their units rather than increasing the UCB inventory, acquire efficient quality control systems, and acquire and preserve UCB units with a greater number of nucleated cells.

Angiotensin I-converting enzyme genotype significantly affects progression of IgA glomerulonephritis in an italian population.

To evaluate the role of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in the progression of immunoglobulin A glomerulonephritis (IgA-GN), genotype distribution in 81 biopsy-proven cases of IgA-GN was studied. A logistic regression model showed that the risk for homozygous DD was not significantly elevated in patients with IgA-GN compared with healthy subjects (odds ratio = 1.16; confidence interval [CI], 0.4 to 3.3). However, the 5-year (78% v 90%) and 10-year (52% v 82%) renal survival rates for 47 patients with serum creatine (Cr) levels of 1.5 mg/dL or less at biopsy was significantly less in DD patients (n = 18; chi2 = 5.41; P = 0.02). The hazard ratio (HR) for DD (multivariate analysis from Cox proportional model after adjustment for known factors of progression, such as hypertension [HPT] and proteinuria [PTO]) was 3.07 (CI, 1.1 to 9.4). The HR for heavy PTO was 6.1 (CI, 1.9 to 19). The association of DD genotype with progression was even more striking when patients with other risk factors (heavy proteinuria) were excluded, as shown by DD-related risk in the absence (HR = 3.6; CI, 1.1 to 12) and presence (HR = 2; CI, 0.4 to 10) of PTO. The risk ratio was further increased by the coexistence of DD + PTO (HR = 9.16; CI, 1.8 to 15.7). Furthermore, in a cross-sectional study among patients with IgA-GN, a logistic regression model showed that the risk for homozygous DD was greater, although not at a statistically significant level in the end-stage renal failure subgroup compared with the normal renal function subgroup (odds ratio = 3.16; CI, 0.7 to 13.7) after adjustment by sex, age at biopsy, HPT, PTO, and therapy. Last, DD was significantly more frequent in those patients who started hemodialysis at an earlier age (chi2 for trend = 6.81; P = 0.009). Our study further supports that ACE genotype is a risk factor not for the development, but for the worsening of IgA-GN clinical course. However, on the basis of current knowledge, we cannot exclude that I/D polymorphism may simply serve as a prognostic marker, eventually linked with other discrete loci involved in the progression of renal damage.

[The Italian Registry of Bone Marrow Donors: genetic structure and recruitment strategy]. / Il Registro Italiano dei Donatori di Midollo Osseo: struttura genetica e strategie di reclutamento.

The genetic structure of the Italian bone marrow donor population was analysed by estimating the HLA-A, -B and -DR gene and haplotype frequencies for the total population and for the Italian administrative regions. The haplotype frequencies were used to predict the probability of finding HLA-compatible donors for Italian patients depending on the registry size, and the probability of recruiting in the different Italian regions a donor with a new phenotype. The analysis of these probabilities allows us to propose strategies for donors recruitment in order to increase the phenotypic variability of the registry, then its efficiency.

["Heart transplantation program" in Piedmont. Results of a 3-year activity]. / "Programma trapianto di cuore" della Regione Piemonte. Risultati dopo tre anni di attività.

Since 1990 the "Heart Transplant Program" has been instituted in the Piemonte Region. Until now the program had regular development according to the number of transplantations and the high quality of clinical results. Sixty heart transplantations has been performed with a 36 month survival close to 80%. Our data demonstrate that after heart transplantation prognosis of end-stage cardiac disease is highly improved either for life expectancy and for quality of life. Our program includes several aspects of scientific research from physiology to clinic, from biochemistry to immunology, from infectivology to pathology, from intensive care to surgery. Several very positive multi disciplinary investigations have been activated.

HLA class II gene frequencies in Italy.

The frequency of HLA alleles at HLA-DR and DQ loci, and that of the related HLA-D specificities, were estimated in the Italian population. 109 healthy unrelated subjects, born in several Italian regions and living in the district of Torino, were studied. DNA typing was achieved by the restriction fragment length polymorphism (RFLP) analysis of HLA-DR beta, DQ alpha and beta genes, hybridizing specific probes with TaqI digested DNAs. The present study allowed to define in more detail the HLA class II polymorphisms in the Italian population.

Altered expression of HLA-A,B specificities on acute lymphoid and myeloid leukaemia blasts.

HLA-A,B specificities were analysed on the neoplastic blasts of a panel of 69 lymphoblastic (ALL) and 50 non lymphoblastic (ANLL) acute leukaemias at onset using the standard lymphocytotoxicity technique. Analysis of the number of detected specificities per locus and, when possible, comparison of the results with those obtained on lymphocytes of the same patients during remission revealed many alterations in the expression of A,B specificities including extra specificities both at the HLA-A and -B loci mainly on lymphoblasts and missed specificities mainly at the HLA-B locus on myeloblasts. Lack of A,B antigens was complete in 6.2% of all tested samples (9% of ANLL) and selective for all the products of one locus in 16.8% of all tested samples (27.7% of ANLL). A decrease of class I molecules on the cell surface was evidenced with MoAb W6/32 on blasts missing detectable serological specificities.

HLA in juvenile dermatitis herpetiformis: clinical heterogeneity correlated with DNA and serological polymorphism.

A group of 30 Italian children affected by Dermatitis Herpetiformis (DH) was analysed for HLA region polymorphisms with both serological and DNA methods. Serological typing was performed on HLA-A, B, C, DR, DQ antigens and C4A, C4B, Bf polymorphisms. DNA RFLPs obtained with TaqI enzyme were investigated with cDNA probes specific for DR beta, DQ alpha and DQ beta genes. The results were correlated with intestinal involvement and age at onset of the disease. The following observations were made: (1) the intestinal biopsies revealed a direct correlation between degree of lesions and age at onset of DH; (2) a significantly increased relative risk (RR) was found for the following HLA antigens: A1 (RR = 2.2), B8 (RR = 6.2), Cw7 (RR = 3.9), C4AQ0 (RR = 7.4), DR3 (RR = 5.2), DR7 (RR = 4.4), DRw53 (RR = 4.7), DQw2 (RR = 6.0); (3) B8 and DR3 were significantly more frequent in patients with severe intestinal lesions; and (4) of the two DR3 subtypes revealed by RFLP typing, only 3.1 showed an increased frequency in DH patients (RR = 8.4). It is suggested that the susceptibility to Juvenile DH is determined by the same genes, within the HLA region, that are associated with Coeliac Disease.

Genetic, immunologic, and environmental heterogeneity of IDDM. Incidence and 12-mo follow-up of an Italian population.

The 1-yr incidence of insulin-dependent diabetes mellitus (IDDM) in a population of the Piedmont and Aosta Valley area of Italy was recorded. Anti-virus antibodies (e.g., Coxsackie B1-6, mumps, cytomegalovirus), islet cell antibodies (ICAs), and HLA-A, -B, -C, and -DR were determined in 74 IDDM patients (38 males, 36 females) and in controls. Total IDDM incidence was 5.0/100,000, and the incidence for those less than 20 yr of age was 11.6/100,000. Anti-virus antibody frequency was not different in IDDM patients and controls. ICAs were present in 58% of IDDM patients at onset and in 30% after 12 mo, and complement-fixing ICAs were found in 39 and 17%, respectively. IDDM was significantly and positively associated with DR3/DR4 and negatively associated with DR2 and DR5. ICA frequency was significantly higher in DR3/DR4 heterozygote patients than in patients without DR3 and DR4. These results suggest that in this IDDM population viral etiology is not evident, ICAs offer only a partial pathogenetic explanation, and genetic and immunologic heterogeneity is evident.