The role of opportunistic quantitative computed tomography in the evaluation of bone disease and risk of fracture in thalassemia major.

OBJECTIVE: Dual-energy X-ray absorptiometry (DXA) remains the cornerstone for osteoporosis evaluation in Thalassemia major. However, several drawbacks have been observed in this unique setting. We sought to determine the correlation between quantitative CT (QCT) and DXA-derived parameters; secondarily, we aimed to investigate the role of the two techniques in predicting the risk of fracture. METHODS: We retrospectively included patients with ß-thalassemia major who had undergone both lumbar and femoral DXA examinations, and CT scans including the lumbar spine, performed for disparate diagnostic issues, within 4 months from the DXA. CT data were examined employing a phantom-less QCT method for bone mineral density (BMD) assessment. We also retrieved any spontaneous or fragility fractures occurring from 1 year before up to 5 years after the date of DXA scans. RESULTS: The 43 patients were included. QCT measures were significantly higher than those determined by DXA. The gap between QCT and DXA values was strongly associated with patient age. The most powerful predictive variable for risk of fracture was the ACR classification based on volumetric BMD obtained by QCT. CONCLUSIONS: DXA provided more negative measures than those determined by QCT. However, QCT seemed to evaluate thalassaemic osteopathy better than DXA, since volumetric BMD was a stronger predictor of fracture.

Dementia and Related Comorbidity: Analysis of 2 Years of Admissions to Italian Hospitals.

BACKGROUND: The aim of the present study was to examine the prevalence of dementia, related comorbidities, and mortality rates in hospitalized elderly patients in Italy. METHODS: Data were obtained from the Italian Ministry of Health and included all discharge records from Italian hospitals concerning subjects aged 65 years or above admitted to acute Internal Medicine during 2 years (n=3,695,278 admissions). Discharge diagnoses were re-classified into 24 clusters, each including homogeneous diseases by the ICD-9-CM code classification. Dementia was identified by the presence of ICD-9-CM codes 290, 294, or 331 series. RESULTS: Patients with dementia represented 7.5% of the sample; compared with those without dementia, they were older and more often female, had a greater length of hospital stay and higher mortality rate. Besides delirium [odds ratio (OR): 54.20], enthesopaties (OR: 2.19), diseases of fluids and electrolytes (OR:1.96), diseases of arteries (OR: 1.69), skin diseases (OR: 1.64), and pneumonia and pleurisy (OR: 1.53) were the diseases more strongly associated with the diagnosis of dementia, independent of other clusters, age, sex, and length of stay. CONCLUSIONS: Some comorbidities are specifically associated with the diagnosis of dementia among hospitalized elderly patients. Overall, these comorbidities describe the typical clinical profile of the patient with advanced dementia and could be treated in the context of the primary care, since they do not require specific skills belonging to hospital settings.

Dementia and in-hospital mortality: retrospective analysis of a nationwide administrative database of elderly subjects in Italy.

AIMS:  To evaluate the relationship between comorbidity and in-hospital mortality in elderly patients affected by dementia. METHODS: Data were obtained from the Italian Ministry of Health and included all discharge records from Italian hospitals concerning subjects aged ≥ 65 years admitted to acute Internal Medicine or Geriatrics wards between January 2015 and December 2016 (3.695.278 admissions). The variables analyzed included age, sex, and in-hospital death. Twenty-five homogeneous clusters of diseases were identified in discharge codes according to the ICD-9-CM classification. RESULTS: Patients with dementia represented 7.5% of the sample (n. 278.149); they were older, more often males (51.9%), and had a higher in-hospital mortality (24.3%) compared to patients without dementia (9.7%). Dementia per se doubled the odds of death (OR 1.98; 95% CI 1.95-2.00), independent of age, sex, and comorbidities. Seven clusters of disease (pneumonia, heart failure, kidneys disease, cancer, infectious diseases, diseases of fluids/electrolytes and general symptoms) were associated with increased in-hospital mortality, independent of the presence/absence of dementia. Among patients with dementia, heart failure, pneumonia and kidney disease on their own substantially doubled/tripled mortality risk. The risk increased from 10.1% (none of selected conditions), up to 28.9% when only one of selected comorbidities was present, rising to 52.3% (OR: 9.34; p < 0.001) when two or more comorbidities were simultaneously diagnosed, besides general symptoms. CONCLUSIONS: Our study confirmed an important increase of in-hospital mortality in older subjects with dementia. Despite a different comorbidity, the conditions associated with in-hospital mortality were substantially the same in patients with or without dementia. Heart failure, pneumonia, and kidney disease identified a high risk of in-hospital mortality among subjects with dementia.

Impact of the preparation method of red cell concentrates on transfusion indices in thalassemia patients: A randomized crossover clinical trial.

BACKGROUND: The average hemoglobin content of red cell concentrates (RCC) varies depending on the method of preparation. Surprisingly less data are available concerning the clinical impact of those differences. STUDY DESIGN AND METHODS: The effects of two types of RCC (RCC-A, RCC-B) on transfusion regime were compared in a non-blinded, prospective, randomized, two-period, and crossover clinical trial. RCC-A was obtained by whole blood leukoreduction and subsequent plasma removal, RCC-B removing plasma and buffy coat first, followed by leukoreduction. Eligible patients were adult, with transfusion-dependent thalassemia (TDT). RESULTS: RCC-A contained 63.9 (60.3-67.8) grams of hemoglobin per unit (median with 1st and 3rd quartile), RCC-B 54.5 (51.0-58.2) g/unit. Fifty-one patients completed the study. With RCC-B, the average pre-transfusion hemoglobin concentration was 9.3 ± 0.5 g/dl (mean ± SD), the average transfusion interval 14.2 (13.7-16.3) days, the number of RCC units transfused per year 39.3 (35.4-47.3), and the transfusion power index (a composite index) 258 ± 49. With RCC-A, the average pre-transfusion hemoglobin concentration was 9.6 ± 0.5 g/dl (+2.7%, effect size 0.792), the average transfusion interval 14.8 (14.0-18.5) days (+4.1%, effect size 0.800), the number of RCC units transfused per year 34.8 (32.1-42.5) (-11.4%, effect size -1.609), and the transfusion power index 272 ± 61 (+14.1%, effect size 0.997). All differences were statistically highly significant (p < .00001). The frequency of transfusion reactions was 0.59% with RCC-A and 0.56% with RCC-B (p = 1.000). CONCLUSION: To reduce the number of RCC units consumed per year and the number of transfusion episodes, TDT patients should receive RCC with the highest average hemoglobin content.

Altered erythroid-related miRNA levels as a possible novel biomarker for detection of autologous blood transfusion misuse in sport.

BACKGROUND: Autologous blood transfusion (ABT) is a performance-enhancing method prohibited in sport; its detection is a key issue in the field of anti-doping. Among novel markers enabling ABT detection, microRNAs (miRNAs) might be considered a promising analytical tool. STUDY DESIGN AND METHODS: We studied the changes of erythroid-related microRNAs following ABT, to identify novel biomarkers. Fifteen healthy trained males were studied from a population of 24 subjects, enrolled and randomized into a Transfusion (T) and a Control (C) group. Seriated blood samples were obtained in the T group before and after the two ABT procedures (withdrawal, with blood refrigerated or cryopreserved, and reinfusion), and in the C group at the same time points. Traditional hematological parameters were assessed. Samples were tested by microarray analysis of a pre-identified set of erythroid-related miRNAs. RESULTS: Hematological parameters showed moderate changes only in the T group, particularly following blood withdrawal. Among erythroid-related miRNAs tested, following ABT a pool of 7 miRNAs associated with fetal hemoglobin and regulating transcriptional repressors of gamma-globin gene was found stable in C and differently expressed in three out of six T subjects in the completed phase of ABT, independently from blood conservation. Particularly, two or more erythropoiesis-related miRNAs within the shortlist constituted of miR-126-3p, miR-144-3p, miR-191-3p, miR-197-3p, miR-486-3p, miR-486-5p, and miR-92a-3p were significantly upregulated in T subjects after reinfusion, with a person-to-person variability but with congruent changes. CONCLUSIONS: This study describes a signature of potential interest for ABT detection in sports, based on the analysis of miRNAs associated with erythroid features.

The effects of blood transfusion on red blood cell distribution width in critically ill patients: a pilot study.

BACKGROUND: Red blood cell distribution width (RDW) is a measure of anisocytosis, generally used in the differential diagnosis of anemia. Recently, RDW was associated with increased mortality in critically ill patients. Red blood cell (RBC) transfusions are potential confounders on RDW values interpretation. The aim of this study was to analyze the changes in RDW after RBC transfusion in intensive care unit (ICU) patients. STUDY DESIGN AND METHODS: This was a prospective, observational study including patients admitted to ICU requiring 1 RBC unit. We analyzed RDW values of the patients at four study points: before RBC transfusion (T1), immediately after transfusion (T2), 24 hours after transfusion (T3), and 48 hours after transfusion (T4). We also collected laboratory data from donors and RBC units. Changes of RDW (ΔRDW) were computed as the difference between baseline RDW value and RDW at each time point after transfusion. RESULTS: We enrolled 36 patients. RDW values increased after transfusion (p < 0.001 at all points vs. baseline), with the highest level at T3. At T3, 34 of 36 patients (94%) had an abnormal RDW value (vs. 26/36, 72%) at baseline (p = 0.023). The maximum ΔRDW for each patient was moderately correlated with the difference between mean corpuscular volume (MCV)donors and MCVpatient (r = 0.478, p = 0.005). Subgroups analysis showed that the maximum ΔRDW was greater in patients with baseline MCV lower than 80 fL or higher than 100 fL (n = 7) or baseline RDW of more than 14.5% (n = 19). CONCLUSION: RBC transfusion significantly increased RDW values. This intervention should be accurately reported in the studies evaluating the prognostic role of RDW.

The effects of storage of red blood cells on the development of postoperative infections after noncardiac surgery.

BACKGROUND: Prolonged storage of red blood cells (RBCs) is a potential risk factor for postoperative infections. The objective of this study was to examine the effect of age of RBCs transfused on development of postoperative infection. STUDY DESIGN AND METHODS: In this prospective, double-blind randomized trial, 199 patients undergoing elective noncardiac surgery and requiring RBC transfusion were assigned to receive nonleukoreduced RBCs stored for not more than 14 days ("fresh blood" group, n = 101) or for more than 14 days ("old blood" group, n = 98). The primary outcome was occurrence of infection within 28 days after surgery; secondary outcomes were postoperative acute kidney injury (AKI), in-hospital and 90-day mortality, admission to intensive care unit, and hospital length of stay (LOS). As older blood was not always available, an "as-treated" (AT) analysis was also performed according to actual age of the RBCs transfused. RESULTS: The median [interquartile range] storage time of RBCs was 6 [5-10] and 15 [11-20] days in fresh blood and in old blood groups, respectively. The occurrence of postoperative infection did not differ between groups (fresh blood 22% vs. old blood 25%; relative risk [RR], 1.17; confidence interval [CI], 0.71-1.93), although wound infections occurred more frequently in old blood (15% vs. 5%; RR, 3.09; CI, 1.17- 8.18). Patients receiving older units had a higher rate of AKI (24% vs. 6%; p < 0.001) and, according to AT analysis, longer LOS (mean difference, 3.6 days; CI, 0.6-7.5). CONCLUSION: Prolonged RBC storage time did not increase the risk of postoperative infection. However, old blood transfusion increased wound infections rate and incidence of AKI.

Best Practices on Radiology Department Workflow: Tips from the Impact of the COVID-19 Lockdown on an Italian University Hospital.

Purpose: The workload of the radiology department (RD) of a university hospital in northern Italy dramatically changed during the COVID-19 outbreak. The restrictive measures of the COVID-19 pandemic lockdown influenced the use of radiological services and particularly in the emergency department (ED). Methods: Data on diagnostic services from March 2020 to May 2020 were retrospectively collected and analysed in aggregate form and compared with those of the same timeframe in the previous year. Data were sorted by patient type in the following categories: inpatients, outpatients, and ED patients; the latter divided in "traumatic" and "not traumatic" cases. Results: Compared to 2019, 6449 fewer patients (−32.6%) were assisted in the RD. This decrease was more pronounced for the emergency radiology unit (ERU) (−41%) compared to the general radiology unit (−25.7%). The proportion of investigations performed for trauma appeared to decrease significantly from 14.8% to 12.5% during the COVID-19 emergency (p < 0.001). Similarly, the proportion of assisted traumatic patients decreased from 16.6% to 12.5% (p < 0.001). The number of emergency patients assisted by the RD was significantly reduced from 45% during routine activity to 39.4% in the COVID-19 outbreak (p < 0.001). Conclusion: The COVID-19 outbreak had a tremendous impact on all radiology activities. We documented a drastic reduction in total imaging volume compared to 2019 because of both the pandemic and the lockdown. In this context, investigations performed for trauma showed a substantial decrease.

Changes in hemoglobin profile reflect autologous blood transfusion misuse in sports.

The changes in hemoglobin (Hb) profile following autologous blood transfusion (ABT) for the first time were studied for anti-doping purposes. Twenty-four healthy, trained male subjects (aged 18‒40) were enrolled and randomized into either the transfusion (T) or control (C) groups. Blood samples were taken from the T subjects at baseline, after withdrawal and reinfusion of 450 ml of refrigerated or cryopreserved blood, and from C subjects at the same time points. Hematological variables (Complete blood count, Reticulocytes, Immature Reticulocytes Fraction, Red-cell Distribution Width, OFF-hr score) were measured. The Hb types were analyzed by high-performance liquid chromatography and the Hemoglobin Profile Index (HbPI) arbitrarily calculated. Between-group differences were observed for red blood cells and reticulocytes. Unlike C, the T group, after withdrawal and reinfusion, showed a significant trend analysis for both hematological variables (Hemoglobin concentration, reticulocytes, OFF-hr score) and Hb types (glycated hemoglobin-HbA1c, HbPI). The control charts highlighted samples with abnormal values (> 3-SD above/below the population mean) after reinfusion for hematological variables in one subject versus five subjects for HbA1c and HbPI. A significant ROC-curve analysis (area = 0.649, p = 0.015) identified a HbA1c cut-off value ≤ 2.7% associated to 100% specificity of blood reinfusion (sensitivity 25%). Hemoglobin profile changed in trained subjects after ABT, with abnormal values of HbA1c and HbPI in 42% of subjects after reinfusion. Future studies will confirm the usefulness of these biomarkers in the anti-doping field.

Deformability and viability of irradiated red cells.

The irradiation of blood components with X or gamma rays is necessary to prevent the graft-versus-host disease, but it also provokes untoward effects. In particular, red cells are damaged and have a decreased in vivo recovery, an increased in vitro haemolysis, and a leakage of potassium in the supernatant. The results of the clinical studies show that the loss of viability progressively increases with the storage after irradiation. On the other hand, the storage before irradiation is inconsequential. The mechanism through which irradiation causes the loss of viability is unknown, but a critical examination of the literature and our results indicate that the erythrocyte deformability is the only parameter related to viability to show sufficiently precocious and important changes. We also tried to identify the mechanism by which irradiation influences deformability and examined, in particular, the changes in the mean cell volume (MCV) and vesiculation. However, the temporal behaviour of both suggests no causal relationship.

Common gene polymorphisms in the metabolic folate and methylation pathway and the risk of acute lymphoblastic leukemia and non-Hodgkin's lymphoma in adults.

Folate and methionine metabolism is involved in DNA synthesis and methylation processes. Polymorphisms in the genes of folate metabolism enzymes have been associated with some forms of cancer. In a case-control study, we evaluated whether four common polymorphisms in methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MS A2756G), and methionine synthase reductase (MTRR A66G) genes may have a role in altering susceptibility to adult acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). We analyzed DNA of 120 adult ALL, 200 NHL, and 257 healthy control subjects. Individual carrying the MTHFR 677TT genotype showed a 3.6-fold decreased ALL risk [odds ratio (OR) 0.28, 95% confidence interval (95% CI) 0.12-0.72] than wild-types. Similarly, MS 2756GG individuals showed a 5.0-fold decreased ALL risk (OR 0.20, 95% CI 0.02-1.45) than wild-types. In combined results, subjects with the MTHFR 677CT/TT and MS 2756AG/GG genotypes revealed a 3.6-fold ALL risk reduction (OR 0.28, 95% CI 0.14-0.58) and those with the MTHFR 677TT and MTRR 66AG genotypes revealed a 4.2-fold ALL risk reduction (OR 0.24, 95% CI 0.06-0.81). Finally, those with the MS 2756AG/GG and MTRR 66AG/GG genotypes revealed a 2.2-fold ALL risk reduction (OR 0.45, 95% CI 0.10-0.85). Single analysis for NHL did not show any significant difference for all the polymorphisms investigated, but in the low-grade NHL subgroup, we found a 2.0-fold risk reduction for the MTRR 66GG homozygous genotype (OR 0.50, 95% CI 0.25-0.99), which was higher (OR 0.37, 95% CI 0.14-0.85) when analyzed in combination with MS 2756AA genotype. These data are in accordance with the hypothesis that polymorphisms in the genes for folate and methionine metabolism might play a greater role in the occurrence of ALL than NHL by influencing DNA synthesis and/or DNA methylation.

Risk of illness, hospitalization and death in a cohort of blood donors in Italy.

OBJECTIVE: The aim of this study was to determine whether blood donors (BDs), compared with non blood donors (nBDs), present significant differences in risk of illness, hospitalization and death. METHODS: All subjects included in the database of the Association of Voluntary Italian Blood Donors of Ferrara entered the study. The analysis only included residents who donated at least once. For each BD, four age- and sex-matched non-donor controls were selected from the master archive of the Province of Ferrara. Then, all hospitalizations of BDs and controls from January 2005 to December 2010 were extracted from the hospital admission and discharge database of the region. RESULTS: During the considered period, 26,140 hospital admissions in BDs and 98,685 in controls were recorded; 11,862 individual BDs and 43,138 nBDs. Compared with controls, BDs were characterized by older age, lower average number of admissions and diagnoses, Charlson comorbidity index score, shorter hospital length-of-stay (LOS), lower mortality rates and higher age at death. Age at death was significantly higher for BDs with longer duration and higher number of donations. In particular, blood donation was not related to an increased risk of malignancies. The main limitation of this study is potential selection bias (i.e. a healthy donor effect). Matching with the control population also has its limitations. CONCLUSIONS: This study confirms that BDs have a lower risk of hospitalization, and, more specifically, do not have an increased risk of malignancies, leukemias, lymphomas and myeloma.

Seasonal variation of platelets in a cohort of Italian blood donors: a preliminary report.

BACKGROUND: Since available data are not univocal, the aim of this study was to explore the existence of a seasonal variation in platelet count. METHODS: The study was based on the database of the Italian Association of Blood Volunteers (AVIS), section of Ferrara, Italy, 2001-2010. Hematological data (170,238 exams referring to 16,422 donors) were categorized into seasonal and monthly intervals, and conventional and chronobiological analyses were applied. RESULTS: Platelets and plateletcrit were significantly higher in winter-autumn, with a main peak in December-February (average +3.4% and +4.6%, respectively, P <0.001 for both). CONCLUSIONS: Although seasonal variations have been reported for several acute cardiovascular diseases, it is extremely unlikely that such a slight increase in platelet count in winter alone may be considered as a risk factor.

A study of leucocyte removal by the RemoweLL cardiotomy reservoir.

BACKGROUND: Cerebral damage is a relatively frequent complication of cardiopulmonary perfusion. Leucocyte activation and lipid microembolisation are among the possible causes. The removal of leucocytes and lipid microparticles from the cardiotomy suction blood could prevent this complication. METHODS: We studied the properties of a cardiotomy reservoir (RemoweLL, EUROSETS), which contains a filtering layer designed to remove some leucocytes and lipid microparticles. The reservoir was loaded with red cell concentrates or whole blood units, some of them containing hyperlipidaemic plasma. The extent of leucocyte and lipid removal was evaluated with reference to the storage age and pre-filtration absolute values of the products. RESULTS: On average, the cardiotomy reservoir removed 35-39% of total leucocytes, with a slight preference for neutrophil granulocytes. This device also retained 26-30% of platelets. The efficiency was not influenced by the storage age of the filtered product nor by the total cell load, within the explored range (323x10(6) - 1,345 x10(6) total leucocytes). Lipid (cholesterol, triglycerides) removal was minimal (about 3-6%). DISCUSSION: The RemoweLL device removed more than a third of the leucocytes from the processed blood. Lipid removal was minimal but the lipid particles in our model (chylomicrons) have a diameter 100-fold smaller than the particles believed to be responsible for clinical effects. This device seems promising and worthy of further studies to document the saturation point of leucocyte removal. On the other hand, lipid removal should be studied in a model more closely resembling the clinical situation in which the device is expected to be used.

Fatal cold agglutinin-induced haemolytic anaemia: a case report.

INTRODUCTION: Cold agglutinin disease usually develops as a result of the production of a specific immunoglobulin M auto-antibody directed against the I/i and H antigens, precursors of the ABH and Lewis blood group substances, on red blood cells. Autoimmune and lymphoproliferative disorders, Mycoplasma pneumoniae and other infections can be associated with the production of cold agglutinins. In its classic presentation with haemolytic anaemia and Raynaud's syndrome, cold agglutinin disease is usually idiopathic. Several factors play a role in determining the ability of a cold agglutinin to induce a haemolytic anaemia such as antibody concentration and temperature range, in particular the highest temperature at which antibodies interact with red blood cells. CASE PRESENTATION: A 48-year-old Caucasian man presented to our hospital with symptoms of extreme asthenia caused by severe anaemia. The transfusion of red blood cells (O Rh-positive), started as prescribed by the emergency guidelines in force without pre-transfusion tests, induced fatal haemolysis because of the presence of high levels of anti-H antibodies in his blood, that reacted with the large amount of H antigen in universal (0) red blood cells. CONCLUSION: Emergency transfusion of universal red blood cells (0 Rh-positive or negative) is usually accepted by the international guidelines in force in emergency departments. In this report we describe a rare complication caused by the very high concentration in the recipient of cold agglutinins and the activation of the complement system, responsible for red blood cell lysis and consequent fatal cardiovascular shock. We conclude that emergency transfusion of universal red blood cells (0 Rh-positive or negative) may be dangerous and its risk should be assessed against the risk of delaying transfusion until the pre-transfusion tests are completed.

The persistence of red cell alloantibodies.

BACKGROUND: Red cell alloantibodies may disappear over time and cause a delayed haemolytic reaction if their past existence is not known before a transfusion. Only few quantitative data have already been presented on this topic. STUDY DESIGN AND METHODS: We retrieved the records of alloantibodies detected between 1989 and 2008 in our institution. All warm-reacting alloantibodies were included, with the exception of ABO antibodies, anti-D in women of childbearing age (it was impossible to rule out Rh prophylaxis) and antibodies produced by transfusion-dependent beta-thalassaemia patients (their transfusion history was too unusual). RESULTS: We found 673 antibodies, produced by 525 patients, which had been tested again after the initial detection. The median follow-up was 319 days. The overall rate of non-persistence was 37%, corresponding to 251 antibodies, produced by 216 patients. Non-persistent antibodies were associated with a longer follow-up (409 vs. 236 days; p=0.012), more tests after detection (2 vs. 1; p<0.001), and a lower maximum score (2+ vs. 3+; p<0.001). Antibody specificity, too, influenced the duration of persistence. Among common antibodies, anti-D was the most long-lived (14% non-persistence); anti-Jka the most short-lived (43% non-persistence). Antibodies detected in the second decade of the study were less persistent (p<0.001). They were also weaker (maximum score: 2+ vs. 3+; p<0.001). This probably reflects the increased sensitivity of the screening tests over the course of time. Age, sex and whether the patient had produced multiple alloantibodies were not significant covariates. A minority of non-persistent antibodies (33/251, 13%) were detected again after a negative result (intermittently-detected antibodies). They had a longer follow-up (885 vs. 341 days; p=0.002), more tests after detection (5 vs. 2; p<0.001), and a higher maximum score (3+ vs. 2+; p=0.001). CONCLUSIONS: Red cell antibodies commonly disappear. To avoid delayed haemolytic reactions, it is necessary to rely on previous records, which should be readily available.

Seasonal variation of pretransfusion hemoglobin levels in patients with thalassemia major.

Patients with thalassemia major often report that they do not maintain their usual pretransfusion hemoglobin concentration during the summer season. We collected 3977 pretransfusion hemoglobin values, amount of blood transfused, and intertransfusion intervals for 94 patients with thalassemia major from 4 centers worldwide. We also assessed the hematocrits of blood donors, the hemoglobin content of units transfused in one center, and the local mean monthly temperatures during the periods of data collection. Pretransfusion hemoglobin levels were significantly lower during the summer in all centers except the one center where monthly temperatures have the least variation throughout the year. A similar relationship to temperature was observed for the hematocrits of blood donors and the hemoglobin content of donor units. This study confirms that pretransfusion hemoglobin levels in patients with thalassemia major are lower in the summertime. Possible mechanisms include expansion of plasma volume with resultant hemodilution in the patient and lower hemoglobin content in donor blood.