Long-term Results of Splenectomy in Transfusion-dependent Thalassemia.

Splenectomy is indicated in transfusion-dependent thalassemia (TDT) only in certain situations. This study aimed to present the effectiveness, complications, and long-term follow-up results of splenectomy in children with TDT. We performed a 30-year single-institution analysis of cases of splenectomy for TDT between 1987 and 2017 and their follow-up until 2021. A total of 39 children (female/male: 24/15) were included. The mean age at splenectomy was 11.2±3.2 years, and their mean follow-up duration after splenectomy was 21.5±6.4 years. Response was defined according to the patient's annual transfusion requirement in the first year postsplenectomy and on the last follow-up year. Complete response was not seen in any of the cases; partial response was observed in 32.3% and no response in 67.6%. Thrombocytosis was seen in 87% of the patients. The platelet counts of 7 (17.9%) patients were >1000 (10 9 /L), and aspirin prophylaxis was given to 22 (56.4%) patients. Complications were thrombosis in 2 (5.1%) patients, infections in 11 (28.2%) patients, and pulmonary hypertension in 4 (10.2%) patients. Our study showed that after splenectomy, the need for transfusion only partially decreased in a small number of TDT patients. We think splenectomy can be delayed with appropriate chelation therapy up to higher annual transfusion requirement values.

[Congenital hemolytic anemias due to erythrocyte membrane and enzyme defects]. / Kongenitale hämolytische Anämien durch Membran- und Enzymdefekte der Erythrozyten.

Erythrocyte membrane and enzyme defects are the most common cause of congenital hemolytic anemias in the Central European population. Diagnostics include erythrocyte morphology, special biochemical tests such as osmotic fragility (AGLT) and EMA. For enzymopenic hemolytic anemias, cost-effective biochemical analysis remains the gold standard, supplemented by molecular genetic diagnostics when appropriate. Therapeutically, near complete splenectomy reduces hemolysis significantly for spherocytosis. The residual spleen at least provides a considerable phagocytic function and better response to immunisation and by inference possibly better protection against severe post-splenectomy infection. For pyruvate kinase deficiency, which is not so rare, a new molecular therapy (Mitapivat) is currently being introduced. In G6PD deficiency, there are very few drugs that cause hemolytic crisis. Sudden onset of hemoglobinuria is an early important hallmark of severe hemolytic crisis in G6PD deficiency and these patients should be hospitalized. Aplastic crises in the setting of parvovirus B19 infection occur in all congenital hemolytic anemias. Transfusion is not preventable in most cases. Iron-excreting treatment is required in the rare patients in need of chronic transfusion.

Research Progress in Chinese Medicine Preparations for Promoting Blood Circulation and Removing Blood Stasis for Cirrhotic Patients with Portal Vein Thrombosis Following Splenectomy.

This article presented an overview of the therapeutic effects of Chinese medicine (CM) preparations for promoting blood circulation and removing blood stasis for patients with portal vein thrombosis (PVT) after splenectomy. Based on published clinical researches of CM preparations for PVT after splenectomy in patients with cirrhotic portal hypertension (CPH), this paper evaluated the incidence of PVT, and explored potential active components and mechanisms of CM preparations. Safflower Yellow Injection, Danshen Injection () Danhong Injection (), and Compound Danshen Dropping Pill () achieved good curative effect alone or combined with anticoagulant therapy. In addition, Compound Biejia Ruangan Tablet () and Anluo Huaxian Pill () can also significantly improve the hemodynamic disorders of portal vein system in patients with cirrhosis. Considering the role of CM preparations in ameliorating the incidence of PVT after splenectomy in patients with CPH, we suggested that future research should provide more attention to CM alone or CM combined with anticoagulant for cirrhosis with PVT.

Survival and complications in patients with haemoglobin E thalassaemia in Sri Lanka: a prospective, longitudinal cohort study.

BACKGROUND: Worldwide, haemoglobin E ß-thalassaemia is the most common genotype of severe ß-thalassaemia. The paucity of long-term data for this form of thalassaemia makes evidence-based management challenging. We did a long-term observational study to define factors associated with survival and complications in patients with haemoglobin E thalassaemia. METHODS: In this prospective, longitudinal cohort study, we included all patients with haemoglobin E thalassaemia who attended the National Thalassaemia Centre in Kurunegala, Sri Lanka, between Jan 1, 1997, and Dec 31, 2001. Patients were assessed up to three times a year. Approaches to blood transfusions, splenectomy, and chelation therapy shifted during this period. Survival rates between groups were evaluated using Kaplan-Meier survival function estimate curves and Cox proportional hazards models were used to identify risk factors for mortality. FINDINGS: 109 patients (54 [50%] male; 55 [50%] female) were recruited and followed up for a median of 18 years (IQR 14-20). Median age at recruitment was 13 years (range 8-21). 32 (29%) patients died during follow-up. Median survival in all patients was 49 years (95% CI 45-not reached). Median survival was worse among male patients (hazard ratio [HR] 2·51, 95% CI 1·16-5·43), patients with a history of serious infections (adjusted HR 8·49, 2·90-24·84), and those with higher estimated body iron burdens as estimated by serum ferritin concentration (adjusted HR 1·03, 1·01-1·06 per 100 units). Splenectomy, while not associated with statistically significant increases in the risks of death or serious infections, ultimately did not eliminate a requirement for scheduled transfusions in 42 (58%) of 73 patients. Haemoglobin concentration less than or equal to 4·5 g/dL (vs concentration >4·5 g/dL), serum ferritin concentration more than 1300 µg/L (vs concentration ≤1300 µg/L), and liver iron concentration more than 5 mg/g dry weight of liver (vs concentration ≤5 mg/g) were associated with poorer survival. INTERPRETATION: Patients with haemoglobin E thalassaemia often had complications and shortened survival compared with that reported in high-resource countries for thalassaemia major and for thalassaemia intermedia not involving an allele for haemoglobin E. Approaches to management in this disorder remain uncertain and prospective studies should evaluate if altered transfusion regimens, with improved control of body iron, can improve survival. FUNDING: Wellcome Trust, Medical Research Council, US March of Dimes, Anthony Cerami and Ann Dunne Foundation for World Health, and Hemoglobal.

Indications et résultats de la splénectomie chez le drépanocytaire au Centre Hospitalier Universitaire de Libreville / Indications and results of splenectomy in sickle cell patients at the University Hospital Center of Libreville

Introduction : la drépanocytose est une affection génétique héréditaire responsable d'une déformation des hématies en «faucilles¼. Elle peut engendrer de nombreuses complications parmi lesquelles la séquestration splénique et l'hypersplénisme. La splénectomie fait partie de l'arsenal thérapeutique, induisant un état d'hyposplénie ou d'asplénie aux conséquences parfois mortelles, surtout chez le sujet drépanocytaire. Le but de ce travail mené au service de chirurgie du centre hospitalier universitaire de Libreville au Gabon, est de déterminer les indications et les résultats à moyen terme de la splénectomie chez le drépanocytaire.Matériel et méthodes : il s'agissait d'une étude rétrospective, descriptive et monocentrique allant d'octobre 2016 à avril 2019. Tous les dossiers des patients drépanocytaires opérés d'une splénectomie seule ou associée à un autre geste chirurgical étaient retenus.Résultats : au total treize patients ont été inclus dans notre étude. L'âge moyen des patients était de 10,7 ans [3-25 ans]. L'indication opératoire était l'hypersplénisme (8 cas), la séquestration splénique (3 cas), et l'infarctus splénique (2 cas). Tous les patients étaient opérés d'une splénectomie totale par laparotomie. La vaccinothérapie et l'antibioprophylaxie post-opératoire étaient réalisées chez tous les patients. Aucune complication post-opératoire immédiate ni aucun décès n'avaient été noté chez tous les patients.Conclusion : l'indication des splénectomies chez le drépanocytaire est dominée par l'hypersplénisme. Dans notre context la splénectomie totale par laparotomie semble être la règle. La vaccination prophylactique est bien administrée. La morbi-mortalité post-opératoire immédiate est nulle.

Introduction: Sickle cell disease is a genetic inherited disorder responsible for the deformation of red blood cells into"sickles". It can lead to many complications including splenic sequestration and hypersplenism. Splenectomy is the indicated gesture. It induces a state of hyposplenia or asplenia with dreadful consequences, sometimes fatal especially in this sickle cell patient. The aim of this work, conducted at the Surgery Department of Libreville University Hospital Center in Gabon, is to determine the indications and results of splenectomy in sickle cell patients.Material and methods: this was a retrospective, descriptive and single-center study from October 2016 to April 2019.All records of sickle cell patients undergoing splenectomy alone or with other surgical procedures were included.Results: a total of thirteen patients were included in our study. The average age of the patients was 10.7 years [3-25years]. The operative indication was hypersplenism (8 cases), splenic sequestration (3 cases), and splenic infarction(2 cases). All patients underwent total splenectomy under laparotomy. Vaccine therapy and postoperative antibiotic prophylaxis were performed in all patients. No immediatepostoperativecomplications or deaths were noted in all patients. Conclusion: the indication of splenectomies in sickle cell disease is dominated by hypersplenism. In our context, total splenectomy under laparotomy was the rule. Prophylactic vaccination is well administered. Immediate postoperative morbidity and mortality is nil.

Risk factors for gastric perforation after cytoreductive surgery in patients with peritoneal carcinomatosis: Splenectomy and increased body mass index.

BACKGROUND: Gastric perforation after cytoreductive surgery (CRS) is an infrequent complication. There is lack of evidence regarding the risk factors for this postoperative complication. The aim of this study was to assess the prevalence of postoperative gastric perforation in patients undergoing CRS for peritoneal carcinomatosis (PC) and to evaluate risk factors predisposing to this complication. METHODS: We designed a unicentric retrospective study to identify all patients who underwent an open upfront or interval CRS after a primary diagnosis of PC of different origins between March 2007 and December 2018 at a French Comprehensive Cancer Center. The main outcome was the occurrence of postoperative gastric perforation. RESULTS: Five hundred thirty-three patients underwent a CRS for PC during the study period and 13 (2.4%) presented a postoperative gastric perforation with a mortality rate of 23% (3/13). Neoadjuvant chemotherapy was administered in 283 (53.1%) patients and 99 (18.6%) received hyperthermic intraperitoneal chemotherapy (HIPEC). In the univariate analysis, body mass index (BMI), peritoneal cancer index, splenectomy, distal pancreatectomy, and histology were significantly associated with postoperative gastric perforation. After multivariate analysis, BMI (OR [95%CI] = 1.13 [1.05-1.22], p = 0.002) and splenectomy (OR [95%CI] = 26.65 [1.39-509.67], p = 0.029) remained significantly related to the primary outcome. CONCLUSIONS: Gastric perforation after CRS is a rare event with a high rate of mortality. While splenectomy and increased BMI are risk factors associated with this complication, HIPEC does not seem to be related. Gastric perforation is probably an ischemic complication due to a multifactorial process. Preventive measures such as preservation of the gastroepiploic arcade and prophylactic suture of the greater gastric curvature require further assessment.

Effects of Omega-3 Polyunsaturated Fatty Acids on Cognitive Function after Splenectomy in Rats.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after abdominal surgery. Several studies have reported that POCD is related to neuroinflammation caused by surgery. Omega-3 polyunsaturated fatty acids (PUFAs) can effectively inhibit the systematic inflammatory response. So, we use fish oil to study the effect of fish oil on inflammation, immunity, and cognitive behavior after splenectomy in rats. METHODS: 60 SD (Sprague-Dawley) rats were randomly divided into control group (group C, n = 20), surgery group (group S, n = 20), and omega-3 (fish oil) intervention group (group F, n = 20). Omega-3 PUFA was injected intraperitoneally from 3 days before operation to 7 days after operation in group F, and normal saline was injected simultaneously in group S. Rats in group S and group F received splenectomy under general anesthesia. Morris water maze behavioral evaluation was performed on the first, third, fifth, and seventh day after operation. The levels of IL-1ß (interleukin-1ß), IL-6 (interleukin-6), TNF-α (tumor necrosis factor-α), SOD (superoxide dismutase), and GSH-PX (glutathione peroxidase) were detected. RESULTS: Serums IL-1ß, IL-6, and TNF-α concentrations in group S and group F were higher than those in group C (P < 0.01), while those inflammatory cytokines in group F were significantly lower than those in group S (P < 0.01); serum GSH-PX levels in group F were higher than group S (P < 0.01). The Morris water maze behavior test performance of group F was better than that of group S (P < 0.05). CONCLUSION: Omega-3 PUFA can effectively improve postoperative inflammatory response, reduce the damage of antioxidant defense system, and improve postoperative cognitive function.

Splenic marginal zone lymphoma associated with hepatitis B virus infection, remission after viral treatment, and splenectomy: A case report and review of the literature.

We report the case of a patient diagnosed with a splenic marginal zone lymphoma with a simultaneous finding of hepatitis B virus infection, who responded to antiviral treatment and splenectomy. We highlighted this association described in the literature and its possible causal role, as well as the available therapeutic choices.

Protective effect of baicalin against cognitive memory dysfunction after splenectomy in aged rats and its underlying mechanism.

Postoperative cognitive dysfunction is a common neurological complication, characterized by impaired learning and memory, that occurs after anesthesia and surgery, especially in elderly patients. The traditional Chinese medicine baicalin is known to have neuroprotective effects. Therefore, we have investigated whether baicalin can improve postoperative cognitive impairment in aged rats after splenectomy. A total of 60 Sprague Dawley rats were randomly divided, equally, into the splenectomy, sham operation (Sham), low-dose baicalin (Baicalin A), medium-dose baicalin (Baicalin B), and high-dose baicalin (Baicalin C) groups. Splenectomy was performed under anesthesia in all groups except for the Sham group, in which an appropriate concentration of saline was administered. The effects of baicalin on learning and memory were examined by the Y-maze behavioral experiments. Although splenectomy had a negative effect on cognitive function in the acute phase, all the rats spontaneously recovered on a postoperative day seven. Nonetheless, in the acute phase, the medium and high doses of baicalin slightly alleviated these effects of the procedure. The protein expression of the inflammatory cytokines tumor necrosis factor-α, Interleukin-6, and Interleukin-1ß was assessed using enzyme-linked immunosorbent assay. Their levels were elevated in the acute phase but were returned to normal with the medium and high dose of baicalin. Real-time PCR analysis of the mRNA expression of the N-methyl-D-aspartic acid receptor TNF-α, which is known to be involved in long-term potentiation, revealed that baicalin promoted its transcription. Thus, the findings indicate that baicalin may improve postoperative cognitive memory dysfunction in postoperative cognitive dysfunction in rats via anti-inflammatory mechanisms and pathways that involve N-methyl-D-aspartate receptor 2B subunit.

Prediction of the Factors Influencing the Shengjing Classification of Portal Vein Thrombosis after Splenectomy for Portal Hypertension in Cirrhosis: A Single-Center Retrospective Case-Control Study.

OBJECTIVE: To compare the survival time of patients with portal vein thrombosis after splenectomy for portal hypertension in cirrhosis and explore the influencing factors of the Shengjing classification. METHODS: Clinical data of 108 patients with portal vein thrombosis after splenectomy in the department of general surgery of our hospital from November 2011 to December 2018 were selected, and a retrospective analysis was performed. RESULTS: Among 108 patients with postoperative PVST formation, 9 had type Ia, 32 type Ib, 39 type IIa, 20 type IIb, 5 type IIIa, 3 type IIIb, and 0 type IV. Survival analysis showed that the difference in survival time distribution among the Shengjing typing groups was statistically significant (P < 0.05). The higher the classification level, the shorter the survival time and the higher the risk of death. The results of a single-factor analysis showed that there were statistically significant differences in the PVST Shengjing typing groups between the preoperative group with or without hepatitis, preoperative d-dimer level, and postoperative day 14 fibrinogen (FIB) level (P < 0.05). Multivariate logistic regression analysis showed that the OR value of higher PVST Shengjing typing in patients with hepatitis was 4.634 times higher than that in patients without hepatitis (95% CI: 1.593-13.478, χ 2 = 7.922, P = 0.005 < 0.05). Preoperative d-dimer volume increased by 1 µg/L; the OR value of higher grade PVST Shengjing typing was 1.001 times higher (95% CI: 1.000-1.002) than that of lower grade PVST Shengjing typing (χ 2 = 8.369, P = 0.004 < 0.05). CONCLUSIONS: The survival time of patients with portal vein system thrombosis after splenectomy was significantly different among Shengjing typing groups, and the higher the classification level, the shorter the survival time and the higher the risk of death. In patients with portal hypertension in cirrhosis and PVST formation after splenectomy, if the preoperative d-dimer level is high or accompanied by hepatitis virus, the formation of PVST will involve a wide range, the disease is more serious, and the prognosis is also poor, so corresponding preventive measures should be taken to avoid the aggravation of PVST.

Risk adapted approach: How to treat splenic marginal zone lymphoma in resource-poor settings? - The real-life experience of a Brazilian cancer treatment center.

BACKGROUND: Splenic marginal zone lymphoma (SMZL) is a rare lymphoid B-cell malignant neoplasm with primary involvement of the spleen. It is a chronic disease, of indolent behavior and prolonged survival. However, 25% of cases have higher biological aggressiveness, propensity for histological transformation to high grade B-cell non-Hodgkin lymphoma and shortened survival. Recognition of these cases of reserved outcome is important for selecting a risk-adapted therapeutic approach in a resource-poor settings. METHODS: We described clinical and epidemiological characteristics, survival analysis and prognostic factors in a retrospective cohort of 39 SMZL patients, treated in Latin America. RESULTS: We observed a predominance of female (71.8%), median age of 63 years and higher incidence of B symptoms (56.4%) and extra-splenic involvement (87.1%) than in European and North-American series. With a median follow-up of 8.7 years (0.6-20.2 years), estimated 5-year overall survival (OS) and progression-free survival (PFS) were 76.9% and 63.7%, respectively. Factors with adverse prognostic impact on OS and PFS were Hb < 100 g/L, platelet count < 100 x 109/L, albumin < 3.5 g/dL, LDH > 480 U/L and high-risk Arcaini and SMZL/WG scores. Despite a relative low number of patients, no superiority was observed among the therapeutic regimens used including rituximab monotherapy, splenectomy and cytotoxic chemotherapy. CONCLUSION: Therefore, in resource-poor settings, where access to immunotherapy is not universal for all SMZL patients, we suggest that first-line should consist on rituximab therapy for elderly patients or with high surgical risk or with at least 1 risk factor identified in our study. Remainders can be safely managed with splenectomy.

Phenotypical and functional abnormalities of circulating neutrophils in patients with ß-thalassemia.

ß-Thalassemia is an inherited single gene disorder related to reduced synthesis of the ß-globin chain of hemoglobin. Patients with ß-thalassemia present variable clinical severity ranging from asymptomatic trait to severe transfusion-dependent anemia and multiple organs complications. Moreover, multiple immune abnormalities are a major concern in ß-thalassemia patients. Aberrant neutrophil effector function plays a pivotal role in infection susceptibility in these patients. In severe and persistent inflammation, immature neutrophils are released from the bone marrow and are functionally different compared with mature ones. Despite some abnormalities reported for thalassemia patient's immune system, few data exist on the characterization of human neutrophils in ß-thalassemia. The aim of this study was to investigate the phenotype and function of circulating neutrophil subsets in patients with ß-thalassemia major and with ß-thalassemia intermedia divided in transfusion-dependent and non-transfusion-dependent. By the use of immunochemical and cytofluorimetric analyses, we observed that patients' CD16+ neutrophils exhibit abnormalities in their phenotype and functions and the abnormalities vary according to the clinical form of the disease and to the neutrophil subset (CD16bright and CD16dim). Abnormalities include altered surface expression of the innate immune receptor CD45, Toll-like receptor 4, and CD32, reduced ability to produce an oxidative burst, and elevated levels of membrane lipid peroxidation, especially in patients with a more severe form of the disease. Overall, our results indicating the occurrence of an immuno-senescent phenotype on circulating neutrophils from thalassemia patients suggest the usefulness of neutrophil feature assessment as a tool for better clinical management of ß-thalassemia.

Management of pyruvate kinase deficiency in children and adults.

Pyruvate kinase deficiency (PKD) is an autosomal-recessive enzyme defect of the glycolytic pathway that causes congenital nonspherocytic hemolytic anemia. The diagnosis and management of patients with PKD can be challenging due to difficulties in the diagnostic evaluation and the heterogeneity of clinical manifestations, ranging from fetal hydrops and symptomatic anemia requiring lifelong transfusions to fully compensated hemolysis. Current treatment approaches are supportive and include transfusions, splenectomy, and chelation. Complications, including iron overload, bilirubin gallstones, extramedullary hematopoiesis, pulmonary hypertension, and thrombosis, are related to the chronic hemolytic anemia and its current management and can occur at any age. Disease-modifying therapies in clinical development may decrease symptoms and findings associated with chronic hemolysis and avoid the complications associated with current treatment approaches. As these disease-directed therapies are approved for clinical use, clinicians will need to define the types of symptoms and findings that determine the optimal patients and timing for initiating these therapies. In this article, we highlight disease manifestations, monitoring approaches, strategies for managing complications, and novel therapies in development.

Local and systemic immunosuppression in pancreatic cancer: Targeting the stalwarts in tumor's arsenal.

Late detection, compromised immune system, and chemotherapy resistance underlie the poor patient prognosis for pancreatic ductal adenocarcinoma (PDAC) patients, making it the 3rd leading cause of cancer-related deaths in the United States. Cooperation between the tumor cells and the immune system leads to the immune escape and eventual establishment of the tumor. For more than 20 years, sincere efforts have been made to intercept the tumor-immune crosstalk and identify the probable therapeutic targets for breaking self-tolerance toward tumor antigens. However, the success of these studies depends on detailed examination and understanding of tumor-immune cell interactions, not only in the primary tumor but also at distant systemic niches. Innate and adaptive arms of the immune system sculpt tumor immunogenicity, where they not only aid in providing an amenable environment for their survival but also act as a driver for tumor relapse at primary or distant organ sites. This review article highlights the key events associated with tumor-immune communication and associated immunosuppression at both local and systemic microenvironments in PDAC. Furthermore, we discuss the approaches and benefits of targeting both local and systemic immunosuppression for PDAC patients. The present articles integrate data from clinical and genetic mouse model studies to provide a widespread consensus on the role of local and systemic immunosuppression in undermining the anti-tumor immune responses against PDAC.

Significance of Amylase Monitoring in Peritoneal Drainage Fluid after Splenectomy: A Clinical Analysis of Splenectomy in 167 Patients with Hepatolenticular Degeneration.

Different kinds of complications after splenectomy in hepatolenticular degeneration patients with hypersplenism have been reported in the past decades, but studies on pancreatic fistula and the corresponding targeted prevention and treatment after splenectomy still remain much unexplored. The present work investigated the pathogenic factors of pancreatic fistula after splenectomy and the variation tendency of amylase in drainage fluid, aiming to verify the significance of monitoring amylase in the abdominal drainage fluid in the early diagnosis of pancreatic fistula after splenectomy. One hundred sixty-seven patients with hepatolenticular degeneration and hypersplenism who underwent splenectomy in the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from January 2016 to August 2018 were selected and analyzed. The amylase in the abdominal drainage fluid was monitored routinely after splenectomy. We also conducted the statistics on the incidence of different types of pancreatic fistula and analyzed the influence factors of pancreatic fistula formation. After splenectomy, biochemical fistula occurred in 11 patients (6.6%), grade B fistula in six patients (3.6%), grade C fistula in one patient (0.6%), and the incidence of pancreatic fistula was 4.2 per cent (biochemical fistula excluded). The amylase in the peritoneal drainage fluid was closely concerned with the incidence of pancreatic fistula according to our statistics. Furthermore, by analyzing the different influence factors of pancreatic fistula, Child-Pugh grading of liver function (P = 0.041), pancreatic texture (P = 0.029), degree of splenomegaly (P = 0.003), and operative method (P = 0.001) were supposed to be closely related to the formation of pancreatic fistula. Monitoring of amylase in peritoneal drainage fluid is regarded as an important physiological parameter in the early diagnosis of pancreatic fistula after splenectomy, which provides effective clinical reference and plays a significant role in preventing the occurrence and development of pancreatic fistula.

Beta-Thalassemia Intermedia: A Single Thalassemia Center Experience from Northeastern Iraq.

OBJECTIVE: To determine the molecular characterization and disease-associated complications of beta-thalassemia intermedia (ß-TI) patients in Sulaymaniyah province, northeastern Iraq. METHODS: A total of 159 ß-TI) patients in Sulaymaniyah province, northeastern Iraq. ß-TI) patients in Sulaymaniyah province, northeastern Iraq. RESULTS: Nineteen different ß-globin gene mutations arranged in 37 various genotypes were determined. The most frequent were IVS-II-I (G>A) (47.2%), followed by IVS-I-6 (T>C) (23.3%) and IVS-I-110 (G>A) (5%). Among disease-related morbidities documented, bone disease amounted to 53% (facial deformity and osteoporosis), followed by endocrinopathies 17.6% (growth retardation and subclinical hypothyroidism), cholelithiasis 13.8%, pulmonary hypertension 11.3%, and abnormal liver function test 7.5%, whereas venous thrombosis, extramedullary hemopoiesis, and leg ulcer were less frequently observed. Age ≥ 35 and female sex were risk factors for cholelithiasis, while age was an independent risk for hypothyroidism and female sex was associated with increased risk for osteoporosis. Mean serum ferritin of ≥1000 µg/L was associated with an increased risk of osteoporosis, whereas chelation therapy was protective for a multitude of other complications. Transfusion, on the other hand, increased the risk of osteoporosis, yet it was protective for cholelithiasis and hypothyroidism. Moreover, splenectomy was protective for cholelithiasis, although it was an independent risk for hypothyroidism. Finally, hydroxyurea was associated with an increased risk of osteoporosis, while it was protective for cholelithiasis. Discussion and Conclusion. ß +-thalassemia mutation had contributed to 41.25 of families with a less severe ß-thalassemia phenotype in the northeastern part of Iraq, justifying the need to investigate the contribution of genetic modifiers in ameliorating disease severity. In addition, the substantial number of ß-TI patients developed disease-related morbidities, which necessitates the need for more appropriate clinical management with earlier intervention.ß-TI) patients in Sulaymaniyah province, northeastern Iraq. µg/L was associated with an increased risk of osteoporosis, whereas chelation therapy was protective for a multitude of other complications. Transfusion, on the other hand, increased the risk of osteoporosis, yet it was protective for cholelithiasis and hypothyroidism. Moreover, splenectomy was protective for cholelithiasis, although it was an independent risk for hypothyroidism. Finally, hydroxyurea was associated with an increased risk of osteoporosis, while it was protective for cholelithiasis. Discussion and Conclusion. ß +-thalassemia mutation had contributed to 41.25 of families with a less severe ß-thalassemia phenotype in the northeastern part of Iraq, justifying the need to investigate the contribution of genetic modifiers in ameliorating disease severity. In addition, the substantial number of ß-TI patients developed disease-related morbidities, which necessitates the need for more appropriate clinical management with earlier intervention.Discussion and Conclusion. ß +-thalassemia mutation had contributed to 41.25 of families with a less severe ß-thalassemia phenotype in the northeastern part of Iraq, justifying the need to investigate the contribution of genetic modifiers in ameliorating disease severity. In addition, the substantial number of ß-TI patients developed disease-related morbidities, which necessitates the need for more appropriate clinical management with earlier intervention.ß-TI) patients in Sulaymaniyah province, northeastern Iraq. ß-TI) patients in Sulaymaniyah province, northeastern Iraq.

The effect of deferasirox on endocrine complications in children with thalassemia.

Endocrine system dysfunctions are the significant complications of excessive iron overload in beta thalassemia patients. The aim of this study was to evaluate the long-term effect of chelation with deferasirox on endocrine complications. The study group consisted of children with beta thalassemia who had been evaluated for the growth and pubertal development, bone metabolism, thyroid/parathyroid functions, glucose metabolism dysfunctions in the department of pediatric hematology of Ankara Diskapi Child Health and Diseases Hematology Oncology Training And Research Hospital between 2009-2011 and reevaluated after deferasirox chelation therapy in 2018. Thirty-one transfusion dependent beta-thalassemia patients were enrolled for the study. Seventeen (54.8%) patients were male and the mean age was 16.9 ± 3.8 (9-23) years. Splenectomy was performed in 11 patients (35.5%). In the initial evaluation, 26 patients (84%) received deferoxamine and/or deferiprone and five (17%) patients received deferasirox as a chelator; in the final evaluation all patients were receiving deferasirox. The mean duration of deferasirox treatment was 5.9 ± 2.02 years (1-10 years). Of the 26 patients who had endocrine complications between 2009-2011, 18 were recovered. In the final evaluation, eight patients (25%) developed new endocrinopathies. The frequency of endocrine complications seen before the deferasirox treatment (83%) was higher than the frequency of complications while receiving deferasirox treatment (25.8%) (p < 0,05). In this study, it was determined that both existing endocrine abnormalities were reduced and recent developed problems were less likely with long-term deferasirox treatment in thalassemia patients.

Thalassemia: Common Clinical Queries in Management.

Beta thalassemia major (TM) is the most frequent form of transfusion-dependent inherited anemia in India. The thalassemia syndromes exhibit enormous variability in their genetic basis and phenotypic expression. The authors recommend that the diagnosis of TM or non-transfusion-dependent thalassemia (NTDT) should not be based on a one-time assessment. Many patients have a chronic anemia that is not severe enough to justify regular transfusions, but the clinical course can evolve with age. Continued observation may reveal that some patients who are considered NTDT will benefit from transfusions later in life. Clinical decision making can be influenced by the perceived difficulty in access to a safe blood supply and the cost of therapy. Here, authors present selected case scenarios that address common issues in the management of TM or NTDT. The recommendations are based on published evidence where available or on the authors' shared experience. Among the topics under discussion are deciding when to start regular transfusions, the role of hydroxyurea in TM, the procedure for blood administration, the use of deferasirox for chelation and monitoring of side effects, the role of splenectomy, and the prospects for gene therapy. In order to achieve an optimal outcome with blood transfusions and chelation therapy over the lifetime, it is essential to adhere to the current guidelines for the management of thalassemia.

Vascular endothelial growth factor and pulmonary hypertension in children with beta thalassemia major / Fator de crescimento endotelial vascular e hipertensão pulmonar em crianças com talassemia beta maior

Abstract Objective: The purpose of this study was to illustrate the association between vascular endothelial growth factor level and pulmonary artery hypertension in children with β-thalassemia major. Method: This case-control study was conducted on 116 children with β-thalassemia major; 58 of them had pulmonary artery hypertension. They were compared to 58 healthy children who were age and sex-matched (control group). Serum levels of vascular endothelial growth factor and echocardiographic assessment were done for all children. Results: Vascular endothelial growth factor serum level was significantly higher in children with β-thalassemia major with pulmonary artery hypertension than in those without pulmonary artery hypertension, as well as in control groups (p < 0.001). Vascular endothelial growth factor serum level had a significant positive correlation with pulmonary artery pressure and serum ferritin, as well as a significant negative correlation with the duration of chelation therapy. Logistic regression analysis revealed that elevated vascular endothelial growth factor (Odd Ratio = 1.5; 95% Confidence Interval, 1.137-2.065; p = 0.005) was an independent risk factor of pulmonary artery hypertension in such children. Vascular endothelial growth factor serum level at a cutoff point of >169 pg/mL had 93.1% sensitivity and 93.1% specificity for the presence of pulmonary artery hypertension in children with β-thalassemia major. Conclusion: Elevated vascular endothelial growth factor serum level is associated with pulmonary artery hypertension in children with β-thalassemia.

Resumo: Objetivo: A finalidade deste estudo foi exemplificar a associação entre o nível de fator de crescimento endotelial vascular e a hipertensão arterial pulmonar em crianças com talassemia beta maior. Método: Este estudo caso-controle foi realizado em 116 crianças com talassemia beta maior; 58 das quais apresentaram hipertensão arterial pulmonar em comparação com 58 crianças saudáveis pareadas por idade e sexo (grupo de controle). Os níveis séricos do fator de crescimento endotelial vascular e a avaliação ecocardiográfica foram realizados em todas as crianças. Resultados: O nível sérico do fator de crescimento endotelial vascular foi significativamente maior em crianças com talassemia beta maior com hipertensão arterial pulmonar que as crianças sem hipertensão arterial pulmonar e os grupos de controle (p < 0,001). O nível sérico do fator de crescimento endotelial vascular apresentou uma correlação positiva significativa com a pressão arterial pulmonar e a ferritina sérica e correlação negativa significativa com a duração da terapia de quelação. A análise de regressão logística revelou que o fator de crescimento endotelial vascular elevado (RC = 1,5; IC de 95%: 1,137-2,065; p = 0,005) foi um fator de risco independente de hipertensão arterial pulmonar nessas crianças. O nível sérico do fator de crescimento endotelial vascular no ponto de corte > 169 (pg/mL) apresentou 93,1% de sensibilidade e 93,1% de especificidade na presença de hipertensão arterial pulmonar em crianças com talassemia beta maior. Conclusão: O nível sérico do fator de crescimento endotelial vascular elevado está associado à hipertensão arterial pulmonar em crianças com talassemia beta.