Pre-transfusion Hb Level Research Articles

Do Transfusion Dependent E-Βeta Thalassemics Behave Differently from Patients with Βeta-Thalassemia Major?

To compare the blood transfusion pattern between children with transfusion dependent Eβ-thalassemia and β-thalassemia major. 168 children (age 3months to 12years) with transfusion dependent Eβ thalassemia and β thalassemia major were admitted to the hospital. 120 children who met our inclusion criteria, were selected and detailed history including various parameters indicating the blood transfusion pattern were recorded. In this study 72 children (60%) of the patients were transfusion dependent Eβ thalassemia. They started receiving blood transfusion (BT) at a later age(p < 0.0001), they received BT less frequently(p = 0.001), the total number of blood transfusions received up to 5years of age were less in number(p < 0.0001), the pre-transfusion Hb levels were higher (p < 0.0001) and the peak ferritin level was much lower in them (p < 0.0001). Their transfusion requirement was much less, need for splenectomy was less (p < 0.006), their spleen span and liver span were also less than the children with β-thalassemia major. Our study clearly depicts that transfusion dependent Eβ thalassemia which is more common in our region shows a wide variation from β thalassemia major patients with respect to various parameters including their transfusion pattern.

Sustained Reductions in Red Blood Cell (RBC) Transfusion Burden and Events in β-Thalassemia with Luspatercept: Longitudinal Results of the Believe Trial

Sustained Reductions in Red Blood Cell (RBC) Transfusion Burden and Events in β-Thalassemia with Luspatercept: Longitudinal Results of the Believe Trial

Longitudinal Effect of Luspatercept Treatment on Iron Overload and Iron Chelation Therapy (ICT) in Adult Patients (Pts) with β-Thalassemia in the Believe Trial

Longitudinal Effect of Luspatercept Treatment on Iron Overload and Iron Chelation Therapy (ICT) in Adult Patients (Pts) with β-Thalassemia in the Believe Trial

Effect of N-Acetylcysteine on Total Oxidant Status in Children With β-Thalassemia Major

β-Thalassemias are due to β-globin gene mutation leading to the absence or reduction of β-globin chains formation. Numerous studies are showing the rising of oxidative stress in β-thalassemia major patients. The study aims to evaluate the effects of N-acetylcysteine (NAC) on total oxidant status and Hb levels in children with β-thalassemia major. This study is a randomized clinical trial in the department of pediatrics, Beni-Suef University during the period between May 2019 and October 2019. The subjects of the study were beta-thalassemia major, the study was conducted on 44 patients that were divided into two groups, 22 patients took NAC at a dose of 10 mg/kg (solvymist syrup or, NAC sachet) orally, for 3 months, and the second group as a non-treatment group. Article results show a significant increase in HB for the treatment group between form the first measurement until the 3rd month. There was a significant decrease between Total Oxidant Status before and after three months in the treatment group. Therefore, NAC may be effective in reducing serum Total oxidant status and increase pre-transfusion Hb levels in children with β-thalassemia major.

AML-192: Transfusion Reactions in Children with Acute Myeloid Leukemia in Armenia: Analysis of 20 Years of Data

Context The incidence and severity of transfusion reactions in children with AML differ from those in adults. Published data on this problem is limited, especially from the developing world. Objective The aim of our nationwide study was to evaluate the necessity of blood products transfusions and the incidence of transfusion reactions among children with acute myeloid leukemia (AML) during their hospitalization in Armenia between 1995 and 2014. Design The medical records of all children with different types of AML receiving treatment in 2 main hospitals (Hematology Center after Prof. R.H.Yeolyan and Muratsan Hospital Complex of Yerevan State Medical University) of Armenia within 20 years (1995-2014) were retrospectively reviewed and analyzed. Results Data of 91 pediatric patients with AML with a median age of 12 y and mean age of 10.7 y were collected. Fifty-six (61.5%) patients were male. From the entire cohort, 61 (67%) patients received RBC transfusions overall 423 times (on average 7 transfusions per patient). Information about pretransfusion Hb level was available in 132 cases: in 102 (77.3%) cases, it was below 70 g/L, in 24 (18.2%) cases, between 70 and 80 g/L, and in 6 (4.5%) cases, it was above 80 g/L. Only one transfusion reaction (chills) was documented. Platelets (PLT) were transfused to 36 (39.6%) patients: 522 (14.5 units per patient) units of whole blood platelets (WBT) were administered overall 292 times (1.8 unit per transfusion). In 149 (51%) transfusions, the pretransfusion PLT levels were below 10 × 109/L. In the entire group, WBT transfusion-related reactions were documented 2 times (1 urticaria and 1 febrile reaction with chills). Twelve packs of apheresis platelets were used and only 1 case of urticaria was reported. 286 packs (6 packs per patient) of fresh-frozen plasma (FFP) were administered to 48 (52.75%) patients. In this subgroup 10 cases of urticaria, 1 case of vomiting, and 1 febrile reaction were documented. Whole blood was transfused to 2 (2.2%) patients 4 times. Conclusions In our study cohort, no life-threatening transfusion reactions were reported for any blood product transfusion, which proves that blood transfusions are quite safe in children with AML. Larger studies need to explore these findings.

Blood Transfusion Frequency and Indications in Yemeni Children with Sickle Cell Disease.

Background Blood transfusion is an essential component in the care of patients with sickle cell disease (SCD), but it might be associated with serious acute and delayed complications. This study was aimed to describe red cell transfusion patterns and indications among hospitalized SCD children in a low-resource setting. Patients and Methods. A retrospective, descriptive study of all children (≤16 years) with SCD who received blood transfusion therapy during their hospital admissions in the pediatric department at Al-Sadaqa Teaching Hospital in Aden, Yemen, for a period of one year. Results Out of 217 hospitalized children with SCD, 169 (77.9%) were transfused and received 275 RBC transfusion episodes. The mean age of transfused children was 6.9 ± 4.6 years and 103 (60.9%) were males, with a male/female ratio of 1.6 : 1 (p=0.004). Hemoglobin (Hb) levels were significantly lower in the transfused than in the nontransfused (Hb 5.5 ± 1.5 vs. 7.7 ± 1.5 g/dL, p=0.03). Pretransfusion Hb levels were ˂7.0 g/dL in 86.2% and ˂5.0 g/dL in 39.3% of patients. Single transfusion was given to 122 (72.2%) and 5 or more transfusions in 9 (4.15%) of patients on different occasions. Simple (top-up) transfusion was used in all transfusion events. Commonest indications for transfusion were anemic crises (41.1%), vasoocclusive crises (VOC) (13.8%), VOC with anemic event (11.3%), acute chest syndrome (8.7%), and stroke (7.3%). Conclusion Intermittent blood transfusion remains a common practice for the management of children with acute SCD complications. Main indications were acute anemic crises, severe pain crises, ACS, and stroke. In limited resource settings, such as Yemen, conservative transfusion policy appears to be appropriate.

Clinical impacts of DNA-based typing and provision of antigen-matched red blood cell units for chronically transfused patients with thalassemia

Blood transfusion, the main therapy for patients with severe thalassemia, is challenged by alloantibodies that can lead to hemolytic transfusion reactions. The use of prophylactic antigen-matched units is recommended, but serologic typing, before the first transfusion, is rarely performed and is not reliable after chronic transfusion. Patient DNA-based typing is a promising strategy, but clinical outcome data are lacking. The aim of this study was to determine the benefits of antigenmatched transfusion guided by DNA-based typing in terms of new alloantibody formation and increases in mean pretransfusion hemoglobin (Hb) levels. We performed DNA-based typing on samples from 24 transfusion-dependent patients with thalassemia who had no serologic phenotyping performed before the first transfusion. These patients were then transfused with antigen-matched donor RBC units that were typed serologically. New alloantibody formation and mean pre-transfusion Hb levels were evaluated after implementing this extended common antigen-matching transfusion protocol. Sixty-three percent of the patients in this study were diagnosed as having beta-thalassemia Hb E. Alloantibodies were already present in 87.5 percent (21/24) of these patients, and most of these antibodies were multiple and/ or unidentified. After the enrollment, there were 717 transfusion episodes comprising 1209 RBC units. The number of RBC units transfused to each patient ranged from 22 to 119 units. At the median duration of 25.5 months (range 10-34 months), no new alloantibodies were detected since the beginning of the protocol. Seventy-four transfusion episodes in six patients were crossmatch-positive due to autoantibodies (patients 2, 4, 8, 9, and 14) or anti-Chido (patient 18) that had been identified before the study. There were no hemolytic transfusion reactions in this study. Five patients (patients 1, 2, 12, 15, and 20) showed increased mean pre-transfusion Hb levels (≥1 g/dL) and one patient (patient 16) had longer intervals between transfusions (compared with those before the protocol), suggesting longer RBC survival, although there was no statistical difference in the whole group. Our study highlights the benefits of DNA-based typing in chronically transfused patients with thalassemia who had no phenotyping data before the first transfusion. Patient DNA-based typing for antigen-matched transfusion is safe in thalassemia and allows us to obtain better-matched blood units for complicated patients.

Health-related quality of life in children with hemoglobin E-?-thalassemia with special reference to iron overload

Background: Hemoglobin (Hb) E disease is the most common Hb variant in Southeast Asia. However, in India, it is prevalent in Eastern India and West Bengal, but relatively rare in rest of the country. Objective: The objective of the study was to study the quality of life (QOL) in Hb E/?-thalassemia children with special reference to iron overload. Materials and Methods: An analytical case–control study on Hb E/?-thalassemia children aged 8–12 years was conducted who were admitted in the thalassemia unit and outdoor basis from the departments of pediatric medicine and hematology. They were evaluated for a period of 1 year and the effect on the QOL was assessed with health-related QOL (HRQOL) score along with psychological assessment. Results: A total of 50 subjects were included in the study. The HRQOL was assessed by PedsQL 4.0 generic core scale along with parent proxy report and psychological assessment was done by childhood psychopathology measurement schedule score. It was found that QOL was significantly better when pre-transfusion Hb level was above 7 g/dl. Conclusion: We found that total summary QOL score was not statistically significant, but the physical domain of QOL score showed statistically significant better score when the duration of blood transfusion is less. Therapy should widen beyond drugs with adequate physical rehabilitation and emotional support.

Northstar-2: Updated Safety and Efficacy Analysis of Lentiglobin Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia and Non-β0/β0 Genotypes

Northstar-2: Updated Safety and Efficacy Analysis of Lentiglobin Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia and Non-β0/β0 Genotypes

Blood utilization in five Chinese hospitals shows low hemoglobin thresholds in medical patients.

The number of red blood cell units transfused per capita in China is lower than in western countries and the reason(s) for the difference is unknown. We randomly chose 5050 transfused patients from five Chinese hospitals. We compared transfused cases to nontransfused controls matched for the same underlying diagnosis. We assessed the pretransfusion hemoglobin (Hb) trigger and other clinical characteristics associated with transfusion. After stratifying by underlying disease, we compared pretransfusion Hb level in Chinese hospitals to 12 US hospitals. In 5050 patients who received transfusion, the pretransfusion Hb levels were lower in medical (6.3 g/dL) compared to surgical patients receiving transfusion postoperatively (8.1 g/dL). In patients with nonsurgical diagnoses, the pretransfusion Hb was much lower than that in the United States; the difference in mean Hb level varied by underlying diagnosis from 0.4 to 1.8 g/dL. In case-control analysis of cases (n = 1356) compared to controls (n = 1201), the pretransfusion Hb showed the strongest association with transfusion. Compared to 10 g/dL, the odds ratio (95% confidence interval) for pretransfusion Hb of 7 to 7.9 g/dL was 37.7 (24.8-57.4). Transfusion triggers in five Chinese hospitals appear comparable to those in the United States for surgical patients; however, medical patients have lower pretransfusion Hb levels (approx. 6 g/dL). Of the factors assessed, the pretransfusion Hb was most strongly associated with transfusion. The clinical impact of lower transfusion thresholds used in China is unknown.

Optimal Hemoglobin Level for Pediatric Sickle Cell Patients Who Undergo Adenotonsillectomy

Background:The prevalence of obstructive sleep apnea syndrome (OSA) in children with sickle cell disease (SCD) is higher than in the general pediatric population. Adenotonsillectomy involves significantly increased risks in patients with SCD because of the need for general anesthesia,which could induce a vaso-occlusive event. Various preoperative regimens have been suggested to reduce peri-operative risks for SCD patients.Objective: We retrospectively reviewed the perioperative management for pediatric SCD patients undergoing adenotonsillectomy. We sought to identify the optimal preoperative hemoglobin (Hb) level for patients to have lowest risk of post-operative complications.Methods: Children between 1 and 18 years old with SCD including HbSS, HbSC, HbS beta thalassemia (Sβ0 and Sβ+) who underwent adenotonsillectomy from 2007 to 2017 were identified at Holtz Children's Hospital. Patients without these diseases who underwent the procedures were collected as a control. The study was approved by the University of Miami Institutional Review Board (IRB). De-identified data were exported to GraphPad Prism version 5.02 to perform the statistical analyses. Means were analyzed by student t test, rates by Chi-squared test. p < 0.05 is considered statistically significant.Results: Thirty-four patients with SCD (mean 7.1 yrs) and 145 controls (mean 7.0 yrs) were identified with adenotonsillectomy (see Table 1). SCD patients had significant longer hospital stay (2.6 versus 0.9 days, p< 0.001), and higher postoperative complication rates than the control group (20.6% vs 4.0%, p= 0.02). Most of the sickle cell patients' complications were hypoxemia (5 out of 7), except one supraventricular tachycardia and one headache. Four out of 7 patients with pretransfusion (pretrx) Hb level above 10 g/dL received manual exchange transfusion to keep Hb over 10 g/dL. None had complication or PICU stay. When patients' pretrx Hb levels was 9-10 g/dL, 5/8 received transfusion without significant complications, with the goal of not increasing post transfusion Hb over 11.5 g/dL. Most patients with pretrx Hb level 7-9 g/dL received simple blood transfusion. For patients with preoperative Hb level 9-11.5 g/dL, the PICU transfer rate was significantly lower than ones with Hb <9 or >= 11.5 g/dL (11.5% vs 60%, p=0.04; see Figure 1). Complication rates were also lower in the Hb 9-11.5 g/dL group, but without statistical difference (19.2% vs 40%, p=0.3). Data is limited by small sample size in the SCD group.Conclusion(s): We concluded that for pediatric SCD patients planning for adenotonsillectomy, it is better to keep the posttransfusion Hb level at least above 9 mg/dL but less than 11.5 g/dL before procedure to avoid significant post operational complications. If pretransfusion Hb level is above 9 mg/dL, exchange transfusion by partial phlebotomy or simple transfusion (not to exceed 11.5 g/dL) may be considered. DisclosuresNo relevant conflicts of interest to declare.

Hemoglobin Utilization in Asplenic and Non-Splenectomized Transfusion Dependent Thalassemia Patients Supported with Pathogen Reduced Red Blood Cell Concentrates in a Phase 3 Study (SPARC)

Introduction: Transfusion dependent thalassemia (TDT) requires regular transfusion of red cell concentrates (RBCC) to prevent the complications of anemia and excessive erythroid expansion. Despite donor testing, long-term transfusion has a substantial cumulative risk of transfusion-transmitted infection (TTI) due to undetected viruses, bacteria, and protozoa. Splenectomized (-S) TDT patients may have greater TTI morbidity than patients with spleens (+S); but may benefit from reduced use of red blood cell concentrates (RBCC) and reduced transfusion iron (Fe) loading. Pathogen reduction (PR) of RBCC with amustaline-glutathione (A-GSH) offers potential to reduce the risk of TTI. Objectives: To determine, the impact of PR-RBCC on hemoglobin (Hb) use, transfused Fe burden, incidence of RBC antibodies, and safety in -S and +S TDT patients. Methods: TDT patients at 3 sites, not stratified by spleen status, were prospectively enrolled in a two- period cross-over study randomized by sequence for RBCC preparation. Leukocyte reduced PR-RBCC (Test) were treated with 0.2mM amustaline and 20 mM GSH, re-suspended in saline-adenine-glucose mannitol (SAGM), and stored up to 35 days at 4°C. Leukocyte reduced conventional RBCC (Control) were suspended in SAGM and stored for up to 35 days at 4°C. Patients received 6 transfusions in each treatment sequence of Test or Control RBCC over ~ 5 months. Clinicians, blinded to RBCC Hb content and treatment sequence, ordered RBCC to maintain targeted pre-transfusion Hb thresholds of ~ 9-10 g/dL. Transfusion intervals or number of RBCC transfused were adjusted for clinical management. The primary efficacy outcome was assessed by non-inferiority (NI) analysis for Hb use (expressed as g/kg body weight/ day) using a pre-specified NI margin (≤ 15% of the observed Control mean). Results: Overall, mean (SD) Hb content (g) of 1024 Test RBCC = 54.6±5.9 (range: 39-73) and of 1008 Control RBCC = 55.6 ± 5.9 (range: 35-74) and varied widely. By intent-to-treat (ITT), 80 patients (40 +S and 40 -S) were transfused. For ITT patients (Table), the baseline Hb level (BL-Hb, g/dL) at first transfusion of Control periods was significantly lower than at Test periods; but the mean number of RBCC transfused, RBCC storage days, total Hb dose (g), and transfusion intervals were not significantly different for Test and Control. ITT analysis for all transfusion episodes showed Hb use for Test RBCC (0.110 g/kg/d) was not different from Control RBCC (0.112 g/kg/day). Non-inferiority was demonstrated (T-C = - 0.002 g/kg/d: 95% CI: -0.005, 0.001). ITT Test patients received a slightly lower mean total Hb dose (- 14g), and mean pre-transfusion Hb levels declined after 6 transfusions (9.4 to 8.8 g/dL). -S patients had lower BL-Hb levels (g/dL) than S+ patients in Test (9.2 vs 9.7) and Control (8.8 vs 9.2) periods (Table). -S patients received a lower mean total Hb dose of Test than Control RBCC (p=0.019); and had a decline in mean pre-transfusion Hb levels during Test periods (from 9.2 to 8.7 g/dL). Transfusion intervals were significantly longer for -S patients than +S patients with both Test and Control RBCC (p Conclusions: Amustaline-GSH PR treatment of RBCCs offers the potential to reduce TTI risk without impacting Hb use or Fe burden in TDT. However, Hb content of Test and Control RBCC varies widely and may contribute to unexpected changes in pre-transfusion Hb levels. Spleen status affected Hb use comparably for PR-RBCC and Control RBCC, and remains an important factor in assessing transfusion requirements and Fe loading. Disclosures Aydinok:TERUMO: Research Funding; Cerus: Honoraria, Research Funding; CRISPR Tech: Other: DMC; Protagonist: Other: SSC; La Jolla Pharmaceuticals: Research Funding; Celgene: Research Funding; Novartis: Research Funding, Speakers Bureau. Piga:Apopharma: Honoraria, Research Funding; Celgene Corp: Membership on an entity9s Board of Directors or advisory committees, Research Funding; La Jolla: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Bluebird Bio: Honoraria; Acceleron: Research Funding; Novartis: Research Funding. Origa:Novartis: Honoraria; Bluebird Bio: Consultancy; Cerus Corporation: Research Funding; Apopharma: Honoraria. Mufti:Cerus Corporation: Employment, Equity Ownership. Erikson:Cerus Corporation: Employment, Equity Ownership. North:Cerus Corporation: Employment, Equity Ownership. Waldhaus:Cerus Corporation: Employment, Equity Ownership. Ernst:Cerus Corporation: Employment, Equity Ownership. Lin:Cerus Corporation: Employment, Equity Ownership. Huang:Cerus Corporation: Employment, Equity Ownership. Benjamin:Cerus Corporation: Employment, Equity Ownership. Corash:Cerus Corporation: Employment, Equity Ownership.

Are We Choosing Wisely with Blood Use? an Assessment of Transfusion Practices

Background: Blood transfusions save lives and improve health; however, unnecessary transfusion practice exposes patients to immediate and long-term negative consequences. One of the 2013 Choosing Wisely®recommendations focused on avoiding liberal red blood cell (RBC) transfusion. The specific recommendation was that in situations where transfusion of RBCs is necessary, transfuse the minimum number of units required to relieve symptoms of anemia or to return the patient to a safe hemoglobin (Hb) range (7-8 gr/dl in stable, non-cardiac inpatients). As part of an initiative to improve the quality of RBC transfusion practice we performed this study to examine RBC transfusion practices by patient- and admission-related characteristics.Methods: A cross-sectional survey of RBC transfusions was conducted at three Jerusalem hospitals in the following departments: intensive care (general, adult), internal medicine, orthopedics, hematology and cardiothoracic surgery. These departments were chosen based on their high volume of RBC use. RBC transfusions were identified from the list of RBC units discharged from the hospital’s blood bank within a specified 30-day period and data were collected daily by trained nurses. Exclusion criteria included patients who underwent liver transplants, patients with solid tumors, patients requiring massive transfusions (≥6) and transfusions given during surgery. Orthopedic and cardiothoracic departments were grouped together as surgical departments and compared to all others (i.e. non-surgical). Off-protocol RBC transfusion was defined in this study as patients receiving>1 RBC unit consecutively or transfusion given to non-bleeding, non-active cardiac patients with Hb levels ≥8 gr/dl. Generalized estimating equations (GEE) method was applied to assess the separate associations of each selected characteristic with off-protocol RBC transfusion, taking into account clustering of observations due to repeated transfusions per patient.Results: During the study period 584 RBC transfusions met inclusion criteria. These transfusions were given to 302 patients, mean age of 67 (±19.5, range 14 to 100) years, of which 162 (53.6%) were female. Mean number of transfusions per patient was 1.9 (±1.3) [range from 1 (in 52.6%) to 8 (in 2) patients]. Nearly all patients (291, 96.4%) had at least one underlying medical condition; hypertension (48.3%), malignancy (33.1%), heart (44.7%), nephrology (32.1%) and pulmonary diseases (32.1%). Antithrombotic therapy was taken by 142 (47%) patients. Of the 584 RBC transfusions, 498 (85.3%) were given in the non-surgical departments and 247 (42.3%) were given to patients who underwent invasive procedures/surgery during the current admission, of which 137 (55.5%) were considered major operations (e.g. open laparotomy, open heart, etc.). Pre-transfusion Hb level was ≥8 gr/dl in 229 (39.2%) transfusions and>1 RBC unit was given consecutively in 96 (16.4%) transfusions. The prevalence of off-protocol RBC transfusion, as defined in this study, was 48.1%. Mean age of patients receiving off-protocol RBC transfusion was higher than those receiving by protocol (67.8±18.2 vs. 60.7±21.8, OR=1.02, 95% CI 1.01-1.03). Off-protocol RBC transfusion was more common in the surgical departments vs. non-surgical (OR=7.4, 95% CI 3.7-14.7). In patients undergoing invasive procedure/surgery, major operations were associated with higher odds of off-protocol RBC transfusion compared to minor procedures (OR=1.7, 95% CI 1.1-2.8). Off-protocol RBC transfusion was not related to presence of underling malignancy, heart, nephrology and pulmonary diseases, but was more common among patients taking antithrombotic therapy (OR=1.7, 95% CI 1.2-2.4). Pre-transfusion recording of patients’ blood pressure, pulse rate and saturation were not associated with off-protocol RBC transfusion.Conclusions: This study demonstrates that almost half of RBC transfusions are not given based on suggested guidelines. Although clinical considerations, such as underlying diseases or patient's pre-transfusion signs, may explain non-adherence to guidelines, no clear pattern was observed in the current study to support this explanation. The study findings highlight the need to further our understanding of clinical decision making leading to RBC transfusion and call for establishing clear guidelines to facilitate wise transfusion-related choices. DisclosuresNo relevant conflicts of interest to declare.

Progression of Liver Fibrosis Can be Controlled Under Adequate Chelation in Transfusion-Dependent Thalassemia (TDT).

BACKGROUND. A substantial proportion of patients with transfusion-dependent beta-thalassemia major suffer from chronic liver disease. Iron overload resulting from repeated transfusions and HCV infection have been implicated in the development of liver fibrosis. The objective of iron chelation is to avoid the complications of siderosis, such as hepatocellular injury. As a matter of fact, adequate chelation therapy is mandatory in order to prevent liver disease progression. In the last few years the availability of different chelating agents (coupled with anti-HCV therapy) allowed control of liver disease due to secondary iron overload. Transient elastography (TE, Fibroscan®) is a non-invasive and rapid diagnostic tool that enables accurate prediction of hepatic fibrosis by measuring liver stiffness (LSM). Patients with TDT could benefit from regular non-invasive assessment of liver fibrosis as an indirect indicator of treatment adequacy and therapeutic compliance.AIM. We investigated the efficacy of adequate iron chelation to prevent the progression of liver fibrosis in TDT patients over a time period of approximately 4 years.MATERIALS AND METHODS. We analysed data in a retrospective cohort study over a 4±1.5-year time period. Ninety-nine patients with beta-thalassemia major (41 M, 58 F, aged 36±6 years), followed at Rare Disease Center, Ca’ Granda Hospital in Milan, were enrolled in the study. All patients received regular transfusions every 2-4 weeks. Chelation therapy was registered using deferasirox (DFX), deferoxamine (DFO), deferiprone (DFP) or a combination of the three. All the participants underwent TE and T2-weighted magnetic resonance imaging (T2*MRI) twice (at baseline,T0 and after approximately 4 years, T1). Liver iron concentration (LIC) was assessed by T2*MRI using the appropriate formula at T0 and T1. LSM was measured according to the following cut-off: <5.0 kPa no fibrosis (F0), 5.1-7.9 kPa mild fibrosis (F1), >7.9 kPa moderate fibrosis (F2), >10.3 advanced fibrosis (F3), >11.9 kPa cirrhosis (F4). We divided our cohort into groups depending on the administered chelating agent and the presence of iron overload defined by a LIC > 4.23 mg Fe/g dry weight (corresponding to a T2* value > 6.3 ms).RESULTS. At baseline the mean pre-transfusion Hb levels was 9.74 ± 1.17 g/dL, the mean iron intake 0.33 ± 0.07 mg Fe/kg/d and median serum ferritin 669.5 ng/ml (range 113-5912). HCV-RNA positivity was found in 33 patients (33%) at T0: 20 patients were treated for hepatitis C during the observation period. The overall mean LSM was 7.4±3.2 kPa, the mean hepatic T2* was 9.92±7.01 ms and the mean LIC was 4.81±3.82 mg/g dw (n=99). Data available at 4±1.5 years showed a significant reduction in liver stiffness (6.6±3.2 kPa, p 0.017), iron overload measured by hepatic T2* (12.84±7.28 ms, p < 0.001) and LIC (3.65±3.45 mg/g dw, p 0.001). This result was confirmed when considering patients with iron overload at the time of the first measurment (n=41). The number of patients with moderate to advanced fibrosis (LSM ≥ F2) decreased, yet not significantly (30% vs 19%, p 0.07). Subjects treated with a stable dose of DFX over the entire period of observation (n=39) showed a reduction of LSM (6.9±2.3 vs 6.06±2.4, p 0.04) and a concomitant improvement of hepatic T2* and LIC values (respectively 11.02±6.57 vs 15.04±6.42 and 3.84±2.81 vs 2.49±1.89, p < 0.001). In this group we observed a substantial decrease in the number of patients with LIC > 4.23 mg Fe/g dw (33% vs 13%, p 0.01). A reduction of LSM, yet not statistically significant due to the limited size of the cohort, was achieved in patients on combined DFO+DFP at T0 and T1 (n=6, 8.6±5.5 vs 7.3±3.8). The group of patients on DFO (n=11) remained stable over time. Patients who underwent anti-HCV therapy showed an even more evident reduction in LSM (9±3 vs 7±3.1, p 0.016).CONCLUSION. These data support evidence on the efficacy of adequate iron chelation therapy and, if necessary, anti-HCV treatment in decreasing or at least controlling the progression of liver fibrosis measured by TE in transfusion-dependent BTM patients. Therapeutic compliance and tailoring of drugs is essential to prevent hepatic injury resulting from siderosis. Moreover, proper chelation and treatment of HCV infection act sinergistically to limit progression of liver disease in TDT patients with active hepatitis C, so that development of cirrhosis could be either prevented or greatly delayed. DisclosuresCappellini:Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Genzyme-Sanofi: Membership on an entity's Board of Directors or advisory committees.

Health Related Quality of Life and its Predictors among Bengali Thalassemic Children Admitted to a Tertiary Care Hospital

To assess the quality of life among thalassemic children and to find out association of quality of life (QOL) with the socio-demographic factors, and clinico-therapeutic profile. This cross sectional descriptive epidemiological study was conducted from July 2011 through June 2012 on 365 admitted thalassemic patients of 5 to 12 y of age in the Burdwan Medical College and Hospital. Parents of the children were interviewed using Paediatric Quality of Life Inventory 4.0 Generic Core Scale. Statistically significant variables in bivariate analysis were considered for correlation matrix where independent variables were found inter related. So, partial correlation was done and statistically significant variables in partial correlation were considered for linear regression. The mean age of 365 thalassemic children was 8.3 ± 2.4 y. Multiple linear regressions predicted that only 70.5 % variation of total summary score depended on duration since splenectomy (31.2 % variation), last pre transfusion Hb level (20.7 %), family history of thalassemia (17.3 %) and frequency of blood transfusions (1.3 %). After splenectomy, thalassemic children could lead a better quality of life upto 5 y only. The betterment of the quality of life needs maintaining pre transfusion Hb level above 7 g/dl. Previous experience of the disease among the family members enriches the awareness among them and helps them to take correct decisions timely about the child and that leads to better QOL. More awareness regarding the maintenance of pre transfusion Hb level should be built up among parents and families where such disease has occurred for the first time.

N-Acetylcysteine Supplementation Reduces Oxidative Stress and DNA Damage in Children with β-Thalassemia

There are several reports that increased oxidative stress and DNA damage were found in β-thalassemia major (β-TM) patients. In this study, we aimed to evaluate the effects of N-acetylcysteine (NAC) and vitamin E on total oxidative stress and DNA damage in children with β-TM. Seventy-five children with transfusion-dependent β-thalassemia (β-thal) were randomly chosen to receive 10 mg/kg/day of NAC or 10 IU/kg/day of vitamin E or no supplementation; 28 healthy controls were also included in the study. Serum total oxidant status (TOS) and total antioxidant capacity (TAC) were measured, oxidative stress index (OSI) was calculated, and mononuclear DNA damage was assessed by alkaline comet assay; they were determined before treatment and after 3 months of treatment. Total oxydent status, OSI, and DNA damage levels were significantly higher and TAC levels were significantly lower in the thalassemic children than in the healthy controls (p < 0.001). In both supplemented groups, mean TOS and OSI levels were decreased; TAC and pre transfusion hemoglobin (Hb) levels were significantly increased after 3 months (p ≤ 0.002). In the NAC group, DNA damage score decreased (p = 0.001). N-acetylcysteine and vitamin E may be effective in reducing serum oxidative stress and increase pre transfusion Hb levels in children with β-thal. N-acetylcysteine also can reduce DNA damage.

Trends in red blood cell transfusion and 30-day mortality among hospitalized patients.

Blood conservation strategies have been shown to be effective in decreasing red blood cell (RBC) utilization in specific patient groups. However, few data exist describing the extent of RBC transfusion reduction or their impact on transfusion practice and mortality in a diverse inpatient population. We conducted a retrospective cohort study using comprehensive electronic medical record data from 21 medical facilities in Kaiser Permanente Northern California. We examined unadjusted and risk-adjusted RBC transfusion and 30-day mortality coincident with implementation of RBC conservation strategies. The inpatient study cohort included 391,958 patients who experienced 685,753 hospitalizations. From 2009 to 2013, the incidence of RBC transfusion decreased from 14.0% to 10.8% of hospitalizations; this change coincided with a decline in pretransfusion hemoglobin (Hb) levels from 8.1 to 7.6 g/dL. Decreased RBC utilization affected broad groups of admission diagnoses and was most pronounced in patients with a nadir Hb level between 8 and 9 g/dL (n = 73,057; 50.8% to 19.3%). During the study period, the standard deviation of risk-adjusted RBC transfusion incidence across hospitals decreased by 44% (p < 0.001). Thirty-day mortality did not change significantly with declines in RBC utilization in patient groups previously studied in clinical trials nor in other subgroups. After the implementation of blood conservation strategies, RBC transfusion incidence and pretransfusion Hb levels decreased broadly across medical and surgical patients. Variation in RBC transfusion incidence across hospitals decreased from 2010 to 2013. Consistent with clinical trial data, more restrictive transfusion practice did not appear to impact 30-day mortality.

Transfusions and patient burden in chemotherapy-induced anaemia in France.

To estimate the patient burden in terms of the time spent on outpatient red blood cell (RBC) transfusions indicated for chemotherapy induced-anaemia (CIA) in patients with cancer in France. A retrospective chart review of patients with cancer receiving an outpatient RBC transfusion was conducted at seven treatment centres in France. Total treatment time for one transfusion visit per patient was measured as the elapsed time between pre- and post-transfusion vital sign assessment, including time from transfusion start to stop. Elapsed time from haemoglobin (Hb) level testing to transfusion start and from blood draw for compatibility testing to transfusion start were recorded. In addition, estimated travel time and distance to the transfusion centre, and clinical and demographic information were collected. A total of 103 patients [63.1% men; mean age 66.2 years, standard deviation (SD) 11.9] were enrolled in the study (1 August 2010-31 October 2010). The four most frequent diagnoses were lung cancer (31.1%), urological cancer (15.5%), gynecological cancer (14.6%) and gastrointestinal/colorectal cancer (14.6%). Mean elapsed time between prevital and postvital sign assessment was 4.0 h [95% confidence interval (CI) 1.9-6.1], including a mean of 3.4 h (95% CI 2.5-4.2) for the transfusion itself. Hb level testing (mean pre-transfusion Hb level 8.0 g/dl, SD 0.8) and blood draw for compatibility testing were completed in a mean of 28.8 h (95% CI 1.3-56.2) and 9.4 h (95% CI 0-21.4) prior to transfusion respectively. Patients' one-way mean travel time to the transfusion centre was 32.9 min (95% CI 28.5-37.4) and mean distance travelled was 25.4 km (95% CI 11.6-39.3). In France, CIA treatment with RBC transfusion is a time-consuming activity for patients that includes multiple trips to a medical facility, blood testing and the transfusion procedure itself. This burden is important to consider in the context of optimizing proactive monitoring and planning for supportive oncology care.

Appropriateness of blood product transfusion in the Obstetrics and Gynaecology (O&amp;G) department of a tertiary hospital in West Africa

Misuse of blood by clinicians was suggested to explain blood shortage in sub-Saharan Africa although based on little evidence. This study evaluated whether routine halving (restricted) of blood requests was justified. On alternated days for 3 months in 2011-2012, restricted or full blood product supply [whole blood (WB), red cell concentrate (RCC)] was provided to the Obstetrics & Gynaecology department (O&G). Patient age, haemoglobin (Hb) level pre- and post-transfusion, clinical condition, blood products request and supply, transfused and returned, clinical outcome were collated. Five hundred and nineteen patients (249 restricted and 270 full supply) received 1001 blood products (94.6% WB, 6.4% RCC). Clinical conditions were severe peri-partum bleeding (72.4%) requiring emergency transfusion (82%) whilst 27.6% of total transfusion was for anaemia, 18% being moderate (8-10 g dL(-1) ). Pre-transfusion Hb level was <6 g dL(-1) in 36.7%, 6-8 g dL(-1) 29.1% and ≥ 8 g dL(-1) in 33.2% of cases. Fifty-five percent of the transfused blood was stored ≤ 1 week. Restricted supply triggered additional request (40%) compared to 10% in full supply mode. Whether with restricted or full supply, blood requests, supply and units transfused/patient were similar (restricted 2.3 and 2.1 unit patient(-1) and full 2.9 and 2.3 unit patient(-1) , respectively). Fatal clinical outcome was 3.1% evenly distributed between supply modes and transfusion reactions 0.8%. O&G clinicians order blood according to clinical need and transfuse 85% of the products supplied. Product supply did not significantly affect use although appropriateness of transfusion was difficult to assess.

Early Mortality in 1000 Newly Diagnosed MDS Patients with Low- and Intermediate-1 Risk MDS in the European Leukemianet MDS (EUMDS) Registry

AbstractAbstract 3830 Background:The EUMDS registry was established to obtain an overview in the real world MDS demographics, diagnostics and disease-management. From April 2008 until December 2010, 1000 newly diagnosed patients with IPSS low and int-1 risk MDS were included in 14 countries and 118 participating centers. The major clinical problems in MDS are the consequences of cytopenias and disease-progression. Therefore, the most important treatment goals are improvement of cytopenias and prevention of leukemia. Objectives:To describe the causes of early mortality and to analyze the outcome of the first 1000 patients in the registry with and without disease-progression at 24 months follow-up. Results:The median age of the population was 74 years (range 18–95), 60% were male. The most frequent co-morbidities were hypertension (46%), diabetes mellitus (18%), arrhythmias (12%), and thyroid diseases (12%). The WHO subgroups are RCMD (39%), RA (19%), RARS (17%), RAEB-1 (13%), RCMD-RS (7%), MDS-U (3%), and del5q (2%). IPSS score (n=935) was 0 in 48%, 0.5 in 31% and 1 in 14% of the patients. WPSS score (n=924) was Very Low in 32%, Low in 38%, Intermediate in 19% and High in 4% of the patients (Table1). 184 of 1000 patients (18%) had started MDS specific treatment within 3 months after diagnosis: this increased to 43% at 24 months of follow-up. 15% of the patients (in 12 of the 14 countries) started ESA treatment at registration and this increased to 31% at 24 months, combined with G-CSF in 7%. At registration, 29% of the patients had received at least one RBC transfusion with a mean pre-transfusion Hb level of 8 g/dL. The percentage of transfusion-dependent (TD) patients remained stable during follow-up with 31%, 29%, 26% and 29% at 6, 12, 18, 24 months of follow-up, respectively. At 24 months, overall survival (OS) is 83%. Median time from date of inclusion until progression to higher risk MDS or leukemia is 293 days. Most patients (123) have died without disease-progression (DP) versus 45 patients who have died after DP at 24 months (Table1). DP has been defined as an increase in bone marrow blasts to a higher WHO category. The main causes of death in patients without DP were infections (21%) and cardiovascular events (11%). The mortality rate in transfusion-independent (TI) and TD patients without DP was 5% and 24%, respectively. In TI and TD patients with DP, the mortality rate was 32% and 66%, respectively (Table1; Graph 1). To define the prognostic relevance of serum ferritin (SF) and TD, the SF levels divided in two groups (1. <1000 μg/L, 2. ≥1000 μg/L) were compared in TI and TD patients and stratified by disease-progression. The mortality rate according to SF at registration in TI patients without DP was 9% and 13%, respectively (HR 1.61, 95%CI 0.49–5.37). The mortality rate according to SF at registration in TD patients without DP was 21% and 56%, respectively (HR 4.79, 95%CI 2.56–8.96) (Table 1). Conclusions:The great majority of deceased lower risk MDS patients have died before they have developed clinical signs of disease-progression. Transfusion-dependent patients without disease-progression have a four times higher mortality rate than transfusion-independent patients. This indicates that the pathophysiology of cytopenias and related complications are a major point of interest in early mortality, especially in patients without disease-progression.Table 1:Overall Survival at 2 years, stratified by disease-progressionTotalNo ProgressionProgressionDiedOverall survival HR (95% CI)1DiedOverall survival HR (95% CI)1N100012345IPSS score:0484521810.5314421.44 (0.96–2.16)170.55 (0.22–1.34)1137221.88 (1.14–3.09)141.52 (0.59–3.89)WPSS score:Very Low31629141Low378531.5 (0.95–2.38)170.48 (0.15–1.56)Intermediate191221.41 (0.81-2.46)131.1 (0.33-3.68)High39124.2 (2.14–8.26)51.84 (0.45–7.55)Transfusions2:No54028171Yes460954.12 (2.65–6.4)381.51 (0.64–3.56)Transfusion-dependent:Ferritin at registration1. <1000 μg/L1763311312. ≥1000 μg/L43184.79 (2.56–8.96)90.76 (0.26–2.21)Transfusions, TD and Ferritin adjusted for age, sex, country, WHO category, cytogenetics, cytopenias, % blasts1Hazard Ratio (HR) (95% Confidence Intervals (CI)): IPSS, WPSS score adjusted for age, sex, country;2At least one red blood cell transfusion recorded at registration or follow-up [Display omitted] Disclosures:No relevant conflicts of interest to declare.