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Abstract Introduction Plasma transfusion is a common therapeutic strategy used to lower international normalized ratio (INR) values in the non-emergent setting. However, due to lack of evidence of its efficacy, standardized guidelines for this practice have not been well established. Methods This retrospective observational cohort study analyzed 276 inpatient encounters that involved plasma transfusions focusing on change in INR values from pre- to post-transfusion, with respect to the following predictor variables: vitamin K co-administration, number of plasma units transfused, order indication and body mass index (BMI). Results The overall average change in the INR was 1.35. Patients who received vitamin K showed an average change of 2.51, while patients that did not receive vitamin K demonstrated an average change of 0.70. Increased numbers of plasma units transfused showed benefit up to three-unit orders. Greater decreases in the INR were observed for patients requiring plasma for anticoagulation reversal or active bleeding. There was no significant difference in the change in INR based on the BMI. By multivariate and regression analyses, the stepwise addition of each successive predictor variable demonstrated an increase in the shared variance in the outcome of the post-transfusion INR: the pre-transfusion INR and vitamin K co-administration alone was not significant (p= 0.45); the additional number of plasma units transfused was significant (R² = 0.13, p < 0.001), and; the subsequent additional plasma order indications (R² = 0.19, p < 0.001) and BMI (R² = 0.18, p < 0.001) were increasingly significant. Conclusion Taking into consideration the combination of multiple predictive factors may aid in a more efficient use of plasma products.

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Abstract Introduction Magnetic resonance imaging (MRI) T2* technique is used to assess iron overload in the heart, liver and pancreas of thalassaemic patients. Optimal iron chelation and expected tissue iron response rates remain under investigation. The objective of this study was to analyse serum ferritin and the iron concentration in the heart, liver and pancreas measured by MRI T2*/R2* during regular chelation therapy in a real-world cohort of patients with thalassemia. Methods We evaluated thalassaemic patients ≥ 7 years old undergoing chelation/transfusion therapy by MRI and assessed serum ferritin at baseline and follow-up from 2004-2011. Results We evaluated 136 patients, 92% major thalassaemic, with a median age of 18 years, and median baseline ferritin 2.033ng/ml (range: 59-14,123). Iron overload distribution was: liver (99%), pancreas (74%) and heart (36%). After a median of 1.2 years of follow-up, the iron overload in the myocardium reduced from 2,63 Fe mg/g to 2,05 (p 0.003). The optimal R2* pancreas cut-off was 148 Hertz, achieving 78% sensitivity and 73% specificity. However, when combining the R2* pancreas cut off ≤ 50 Hertz and a ferritin ≤ 1222 ng/ml, we could reach a negative predictive value (NPV) of 98% for cardiac siderosis. Only 28% were undergoing combined chelation at baseline assessment, which increased up to 50% on follow up evaluation. Conclusions Chelation therapy significantly reduced cardiac siderosis in thalassaemic patients. In patients with moderate/severe liver iron concentration undergoing chelation therapy, ferritin levels and myocardium iron improved earlier than the liver siderosis.

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Abstract Introduction The demand for apheresis platelets has increased in the recent past and the shrinking donor pool has shifted the trend to collection of double-dose or higher yield of platelets. Objective The present study aimed to determine the effect of double-dose plateletpheresis on the target yield and donor platelet recovery. Methods The study was conducted on 100 healthy plateletpheresis donors, 50 of whom were in the study group, which underwent double-dose plateletpheresis (DDP), and 50 of whom were in the control group for single-donor plateletpheresis. Pre- and post-procedure samples of donors were subjected to a complete blood count. The DDP product was sampled for platelet yield and then split into two parts. Platelet yield, collection efficiency, collection rate, recruitment factor and donor platelet loss were calculated. Results The mean platelet yield in the SDP was 4.09 ± 1.15 × 1011 and in the DDP, 5.93 ± 1.04 × 1011. There was a significant correlation between the pre-donation platelet count and platelet yield. The total of platelets processed for the SDP were 5.42 ± 1.08 × 1011 and for the DDP, 7.94 ± 0.77 × 1011. The collection efficiency was 71.93 ± 25.14% in the SDP and 72.94 ± 16.28% in the DDP, while the collection rates were 0.78 × 1011 and 0.94 × 1011 per minute, respectively. The average recruitment factor observed was 0.98 in the SDP, while it was 0.99 in the DDP. The mean platelet loss observed in the SDP was 35.55 ± 8.53% and in the DDP, 37.76 ± 8.65%. Conclusion The double-dose plateletpheresis supplements the platelet inventory in developing countries where the apheresis donor pool is limited. It is prudent to ensure stringent donor selection criteria for donors donating high-yield platelet products, thus enhancing donor safety and retention.

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Abstract Background Elevated serum progranulin (PGRN) levels have been associated with a wide range of different human malignancies. However, data available on the role of PGRN in hematological malignancies are limited. Methods Measurement of the PGRN level in serum of adult de novo acute myeloid leukemia (AML) patients using enzyme-linked immunosorbent assay (ELISA) was performed. Results The mean serum PGRN level in AML patients was higher than that in controls (346.08 pg/ml ± 64.46 vs 155 pg/ml ± 63 respectively; p= 0.001). After a mean duration of follow-up equaling 140 days, patients with high serum PGRN (i.e., higher than 370.5 pg/ml) had inferior overall survival (OS) in comparison to patients with low serum PGRN (i.e., lower than 370.5 pg/ml) (OS = 25% vs 60.7%, mean survival = 107 days vs 256.5 days, p= 0.007). On the other hand, remitted patients on day 28 with high serum PGRN (i.e., higher than 307.5 pg/ml) did not differ from those with low serum PGRN (i.e., lower than 307.5 pg/ml) regarding disease-free survival (DFS) (DFS = 78.6% vs. 87.5%, mean survival = 301.3 days vs. 283.5 days, p= 0.789). Moreover, the serum PGRN level was associated with inferior OS (p= 0.024) on multivariate analysis. Conclusion Adult de novo AML patients have elevated serum PGRN levels and a high PGRN level is associated with an inferior OS.

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Abstract Introduction Hemophagocytic lymphohistiocytosis (HLH) is a rare clinical laboratory condition with high mortality rates, resulting from ineffective overactivation of the immune system. Data in the Brazilian literature is scarce, contributing to the challenge in standardizing conducts and performing an early diagnosis of HLH. Objective To describe the clinical, laboratory, and evolutionary findings on HLH patients treated at a pediatric hospital. Methods This is an observational, cross-sectional and retrospective study on children diagnosed with HLH, hospitalized between 2009 and 2019. The diagnostic criteria were those described in the Histiocyte Society protocol. The authors evaluated HLH patient laboratory tests, myelograms and bone marrow biopsies, clinical characteristics and therapy. Results Twenty-three patients were included, 52.2% of whom were males. The age at diagnosis ranged from one to one hundred and eighty months. Four cases were classified as Primary HLH and nineteen, as Secondary HLH. The main triggers were infections and rheumatological diseases. All children had bicytopenia, and 95.4% had hyperferritinemia. Nineteen patients had liver dysfunction, sixteen had neurological disorders and fourteen had kidney injury. Pulmonary involvement was seen in 61.9%, acting as a worse prognosis for death (p= 0.01). Nine patients underwent the immuno-chemotherapy protocol proposed in the HLH 2004. The time to confirm the diagnosis varied from five to eighty days. The lethality found was 56.3%. Conclusions The present study is the most extensive retrospective exclusively pediatric study published in Brazil to date. Despite the limitations, it was possible to demonstrate the importance of discussing HLH as a pediatric emergency.

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Abstract Introduction The Acute Leukemia-European Society for Blood and Marrow Transplantation (AL-EBMT) risk score was recently developed and validated by Shouval et al. Objective To assess the ability of this score in predicting the 2-year overall survival (OS-2), leukemia-free survival (LFS-2) and transplant-related mortality (TRM) in acute leukemia (AL) adult patients undergoing a first allogeneic hematopoietic stem cell transplant (HSCT) at a transplant center in Brazil. Methods In this prospective, cohort study, we used the formula published by Shouval et al. to calculate the AL-EBMT score and stratify patients into three risk categories. Results A total of 79 patients transplanted between 2008 and 2018 were analyzed. The median age was 38 years. Acute myeloid leukemia was the most common diagnosis (68%). Almost a quarter of the cases were at an advanced stage. All hematopoietic stem cell transplantations (HSCTs) were human leukocyte antigen-matched (HLA-matched) and the majority used familial donors (77%). Myeloablative conditioning was used in 92% of the cases. Stratification according to the AL-EBMT score into low-, intermediate- and high-risk groups yielded the following results: 40%, 12% and 47% of the cases, respectively. The high scoring group was associated with a hazard ratio of 2.1 (p= 0.007), 2.1 (p= 0.009) and 2.47 (p= 0.01) for the 2-year OS, LFS and TRM, respectively. Conclusion This study supports the ability of the AL-EBMT score to reasonably predict the 2-year post-transplant OS, LFS and TRM and to discriminate between risk categories in adult patients with AL, thus confirming its usefulness in clinical decision-making in this setting. Larger, multicenter studies may further help confirm these findings.

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Abstract Introduction Sickle cell anemia is a monogenic disorder caused by a mutation in the β-hemoglobin gene, resulting in sickle hemoglobin that can polymerize. Presentation and clinical course have significant inter-individual variability and classifying these patients for severity is a challenge. Methods We applied hierarchical clusters with 10 routine laboratory tests to understand if this grouping could be associated with clinical manifestations. We included 145 adult homozygous patients (SS) at an outpatient clinic in a retrospective study. Results We found five clusters by counting those that had been differentiated by unconjugated bilirubin, reticulocytes, LDH, leukocytes, lymphocytes and monocytes. When comparing groups to clinical findings, the clusters were different only for liver abnormality. Cluster 3 had the lower median of reticulocytes, LDH, leukocytes, lymphocytes and monocytes and a higher percentage of patients under treatment. Clusters 4 and 5 had higher frequencies of liver impairment and higher medians of reticulocytes, LDH, leukocytes, lymphocytes and monocytes. Hemolysis and inflammation seemed to influence the grouping. Conclusion In our study, cluster analysis showed five groups that exhibited different degrees of inflammation and hemolysis. When comparing clinical data, the result was different only for the criteria of liver abnormality.

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Abstract Introduction During pregnancy, women are at an increased risk of developing iron-deficiency anemia. Objective The objective of this study was to assess the diagnostic performance of the reticulocyte hemoglobin equivalent (RET-He) in the early detection of iron-deficiency anemia in a group of pregnant women and to establish a reference range for this parameter in a group of control individuals. Method: A total of 60 patients and 130 control subjects were included in the study. Blood samples collected from the subjects were submitted to a complete blood count and a serum ferritin test and the data were analyzed by comparing the groups and ROC curves. Results The reference range found for the RET-He was between 29.75pg and 38.24pg, with a median of 35pg. The receiver operating characteristic (ROC) curve analysis for the ferritin parameter showed an area under the curve of 0.732 for the RET-He, 0.586 for hemoglobin, 0.551 for the mean corpuscular hemoglobin concentration and 0.482 for the mean corpuscular volume. Conclusion Early diagnosis of iron deficiency anemia in pregnancy is essential to prevent damage to both maternal and fetal health. The RET-He presents an excellent potential as an auxiliary tool for the diagnosis of iron deficiency in pregnant women.

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Abstract Introduction Phagocytosis of autoantibody-sensitized coated platelets through Fc gamma receptors on phagocytic cells is an important mechanism of thrombocytopenia in primary immune thrombocytopenia (ITP). Objective We aimed to investigate the contribution of the FcγRIIa and FcγRIIIa genes polymorphism to the risk of ITP and their association with disease characteristics in Egyptian children. Methods A case control study was conducted on eighty children with primary ITP and eighty age and sex healthy matched subjects as a control group. The FcγRIIa and FcγRIIIa genes polymorphism was detected using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results We found that the FcγRIIa‐131H and ‐131R allele frequencies were 51.3 % and 48.7%, respectively, in children with ITP, versus 75% and 25%, respectively, in controls (p= 0.002). The compound heterozygous HR genotype was significantly higher in ITP patients (p < 0.05). The FcγRIIIa-158F and ‐158V allele frequencies were 46.3% and 53.7%, respectively, in children with ITP, versus 70% and 30%, respectively, in controls (p= 0.002). The compound heterozygous VF genotype was significantly higher in ITP patients (p < 0.05). The combined HR/FV genotype was 47.5% in ITP patients, versus 10% in controls (p < 0.001). No significant difference was found between children with newly diagnosed ITP and those who developed chronic ITP, regarding the frequency distribution of the FcγRIIa and FcγRIIIa alleles and genotypes (p > 0.05). Conclusion There is a possible association of the FcγRIIa and FcγRIIIa genes polymorphism with the risk for, and genetic susceptibility to ITP in Egyptian children, but large-scale studies are still needed to support our findings.

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Abstract Introduction Hyperglycemia occurs in Acute Lymphoblastic Leukemia (ALL) due to chemotherapeutic agents and may be stress-induced. Given the potential impact of hyperglycemia on the clinical outcomes of ALL patients, we sought to determine the association of hyperglycemia with the development of infectious complications. Methods This is a retrospective cohort involving adult Filipino ALL patients admitted at a tertiary referral center. Patients were stratified according to blood glucose levels and infections were classified into microbiologically and clinically defined infections. Logistic regression was performed to determine whether hyperglycemia was associated with the development of infectious complications. Results Of the 174 patients admitted for ALL, only 76 patients (44%) underwent blood glucose monitoring and were thus included in this study. Hyperglycemia was observed in 64 patients (84.21%). Infectious complications were seen in 56 patients (73.68%), of whom 37 patients (48.68%) had microbiologically defined infections and 19 (25%) had clinically defined infections. The respiratory tract was the most common site of infection and gram-negative bacteria were the predominant isolates. Hyperglycemia significantly increased the likelihood of infectious complications, particularly at blood glucose levels ≥ 200 mg/dL. Conclusion Hyperglycemia is associated with an increased likelihood of infectious complications in Filipino ALL patients. With sepsis being one of the main causes of mortality in this population, our study provides compelling evidence for us to consider routine blood glucose monitoring in order to manage and potentially decrease the occurrence of infections in these patients.

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Abstract Introduction Cancer-associated thrombosis is a leading cause of morbidity and mortality in malignancy patients. Prophylactic anticoagulation is under-utilized and the cost of low-molecular-weight heparin (LMWH) and direct oral anticoagulants is a major barrier in developing countries. Material and methods A retrospective analysis was performed of all cancer-associated thrombosis patients attending the thrombosis clinic at a tertiary-level referral hospital based in North India between 2011 and 2015. Patient demographics and disease-related parameters were collected and analyzed. Results A total of 771 patients attended the thrombosis clinic during study period, of which 64 cases were malignancy-associated. Of these, 56% of the patients were female and 20% were bedridden. The median age was 48.5 years, adenocarcinoma (48%) being the most common histological subtype. Gynecological malignancies (30%) were the most common malignancies, followed by genitourinary (11%) malignancies. Most of the cases occurred during first year of diagnosis (51%), and only 14% occurred after 3 years. Most of the patients were on combined treatment. Almost 40% of the patients developed thrombosis within 30 days of surgical treatment. Lower limb thrombosis was the most commonly seen type (56%), while abdominal and pulmonary thrombosis were both seen in 5%. Patients were managed with LMWH and vitamin K antagonists (84.3%) and only 6.25% with LMWH alone. Direct oral anticoagulants were not commonly used during the study period. Discussion At the hospital studied, most of the cases occurred early in the disease course. Postoperative prophylaxis could have contributed towards reducing thrombosis in the peri-operative period. Early suspicion and prompt treatment can improve quality of life in such patients.

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Abstract Introduction Acute myeloid leukemia (AML) is a heterogeneous disease and approximately one-third of its carriers do not have evident genetic abnormalities. The mutation of specific molecular markers, such as fms-like tyrosine kinase 3 (FTL3) internal tandem duplication (ITD), FLT3 tyrosine kinase domain (TKD) and nucleophosmin (NPM1), are associated with an adverse and favorable prognosis, respectively. Objective The objective was to determine the prevalence of FLT3/ITD and NPM1 in Chilean patients and their association with clinical data and prognosis. Method and Results Two hundred and thirty-two children were studied between 2011 and 2017, the median being 8.6 years (ranging from 1 to 18 months). Acute promyelocytic leukemia (APL) was diagnosed in 29%. The FLT3/ITD-mutated in non-promyelocytic AML was at 10% (14/133) and the FLT3/TKD, at 3.7% (2/54). In APL, it was at 25.4% (16/63). In non-promyelocytic AML, the FLT3/ITD-mutated was associated with a high leucocyte count, the median being 28.5 x mm3 (n= 14) versus 19.4 x mm3 (n= 119), (p= 0.25), in non-mutated cases. In APL, the median was 33.6 x mm3 (n= 15) versus 2.8 x mm3 (n= 47), (p < 0.001). The five-year overall survival (OS) in non-promyelocytic AML with non-mutated and mutated FLT3/ITD were 62.7% and 21.4%, respectively, (p < 0.001); the 5-year event-free survival (EFS) were 79.5% and 50%, respectively, (p < 0.01). The five-year OS in APL with non-mutated and mutated FLT3/ITD was 84.7% and 62.5%, respectively, (p= 0.05); the 5-year EFS was 84.7% and 68.8%, respectively, (p= 0.122). The NPM1 mutation was observed in 3.2% (5/155), all non-promyelocytic AML with the normal karyotype. Conclusion The FLT3/ITD mutation was observed more frequently in APL and associated with a higher white cell count at diagnosis. However, the most important finding was that the FLT3/ITD mutation was associated with a shorter survival in non-promyelocytic AML.

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Abstract Objective To evaluate the efficacy and safety of romiplostim (thrombopoietin-receptor agonist) in the treatment of pediatric immune thrombocytopenia (ITP). Methods Searches were conducted in MEDLINE, EMBASE, LILACS, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov (from January 2011 to August 2021). Randomized controlled trials (RCTs), double-blind, comparing romiplostim with a placebo in pediatric persistent or chronic ITP were included. The primary outcome was the overall response rate (platelets ≥ 50 × 109/L) in the absence of rescue therapy for at least two consecutive weeks. The secondary endpoints were the minimization of clinically significant bleeding and the necessity for rescue treatments and the maximization of safety (incidence of overall adverse events) and durable response (maintaining platelet counts for at least twelve weeks). Results Two double-blind randomized placebo-controlled trials (84 participants) were included in this systematic review. Our data showed that, compared to the placebo group, the proportion of patients achieving durable platelet response was significantly higher in the romiplostim group (p= 0.003, RR = 6.34, 95%CI = 1.89 - 21.23), as was the overall response in the romiplostim group (p= 0.002, RR = 3.62, 95%CI = 1.63 - 8.03). Significant bleeding incidents (p= 0.49), overall adverse events (p= 0.71) and the need for rescue treatment (p= 0.13) were not statistically different between the romiplostim and placebo groups. Conclusions Romiplostim might improve both durable and overall platelet response in children and adolescents with ITP, compared to a placebo. More clinical trials are needed to evaluate the efficacy and safety of romiplostim and to compare it with other second-line treatments that are being used in pediatric ITP.