Correlation of Antithrombin Functional Status and Levels with Liver Fibrosis in Patients with Hepatitis C.

BACKGROUND: Abnormal levels of coagulation factors and their inhibitors have shown association with liver diseases. The objective of this study was to determine the qualitative and quantitive status of antithrombin (AT) in patients with chronic liver disease associated hepatitis C infection and their correlation with severity of liver fibrosis. METHODS: In this study, 75 (43 male and 32 female) known patients with chronic liver disease associated hepatitis C infection were enrolled. AT activity and quantitative immunoassays were carried out using Stachrom AT reagent kit (Diagnostica Stago, France) and Liatest AT reagent (Diagnostica Stago, France), respectively. Hepatic biopsies were obtained and graded for liver fibrosis from all study participants. RESULTS: Of the 75 patients, 45 had normal AT while 30 showed lower activity of AT. Similarly, the quantitative assay showed reduced levels of AT in 30 patients and normal levels in 45 patients. CONCLUSIONS: In the early stages of liver fibrosis, AT activity and antigenic levels were found to be normal or minimally affected. While advanced stages of the disease showed markedly reduced levels of AT and activity. Hence, it can be concluded that the degree of fibrosis affects the status of AT.

Prevalence of Rh and K phenotypes among blood donors from different ethnicities in Samtah (Southwestern Region) Saudi Arabia.

INTRODUCTION: Rh and Kell blood group systems are amongst the most important blood group systems; being highly immunogenic after ABO system. The aim of this study was to evaluate the frequencies of Rh antigens, haplotypes and K antigen among blood donors belonging to various ethnicities in Samtah, Jazan, Saudi Arabia. METHODS: This study was conducted during January 2019 and August 2020 at Samtah General Hospital, Samtah. Records of all blood donors recruited during this period were included for data acquisition. A total of 4977 blood donors' records were reviewed and data were analysed. A total of 3863 donors' results were considered in the final analysis. RESULTS: In comparison to Saudi blood donors, C antigen was less frequent in Sudanese donors (69.7% and 34.0%), the c antigen was less frequent in Indian (79.2% and 59.3%) and Philippine (79.2% and 40.0%) donors and more frequent in Sudanese (79.2% and 97.9%) donors, the E antigen was less frequent in Yemini (27.0% and 19.5%) and the e antigen was more frequent in Yemini (96.7% and 99.2%) donors. The DcE haplotype was less frequent (3.1% and 0.7%) and the ce haplotype was more frequent (4.3% and 7.6%) in Yemini donors. The K antigen was less frequent in Pakistani (11.9% and 4.1%; p = .041) and Indian (11.9% and 1.9%; p = .023) donors. CONCLUSION: Rh and K antigens showed marked variations in their frequencies among blood donors of different ethnicities. Utilization of blood from various ethnicities warrant extended phenotyping of Rh and K antigens to avoid the risk of alloimmunization in multiply transfused patients.

Utilization of Discriminant Formulas in the Differentiation of Alpha Thalassemia, Beta Thalassemia, and Iron Deficiency in Premarital Setting.

BACKGROUND: Iron deficiency and thalassemia are two commonly encountered microcytic and hypochromic anemias. The primary objective was to find the best discriminant formula between alpha thalassemia and iron deficiency to be used in premarital screening centers. The secondary objective, was to find cutoff values that might differentiate alpha thalassemia, beta thalassemia, and iron deficiency collectively. METHODS: A total of 224 females divided into four groups (normal, alpha thalassemia, beta thalassemia, and iron deficiency) were recruited in this study after carrying out complete blood count, hemoglobin electrophoresis, serum ferritin, and molecular analysis. Based upon the laboratory data, 26 discriminant formulas (DF) were applied to differentiate alpha thalassemia, beta thalassemia, and iron deficiency anemia. Receiver Operating Characteristic (ROC) curve was constructed and sensitivity, specificity, and Youden's index were determined. RESULTS: In this study, Shine and Lal, Ehsani, Telissani, Sirachainan, Hisham, Kandhro 2, and Mantos indexes showed 100% sensitivity, specificity, Youden's index, and 1.00 AUC for differentiating alpha thalassemia from iron deficient group. Formulas that showed best sensitivity and specificity (100%) in the discrimination of beta thalassemia and iron deficiency were Mentzer, Shine & Lal, Sarivastava & Bevington, and Sirachainan index (AUC 1.00). AUC of Mentzer index was lower (0.988 vs. 1.00) in differentiating alpha thalassemia and iron deficiency than beta thalassemia and iron deficiency. CONCLUSIONS: Almost all discriminant formulas can be utilized for the prediction of microcytic anemia in a premarital setup after excluding beta thalassemia; however, further confirmation is mandatory for genetic counselling and iron supplementation. Furthermore, Bordbar, Kerman index I, and Huber-Herklotz index showed the lowest performance in the discrimination of alpha thalassemia and iron deficiency.

Discrimination of Iron Deficiency, Alpha and Beta Thalassemia on the Basis of Red Cell Distribution Width and Reticulocyte Indices.

BACKGROUND: The two major causes of microcytic anemia are iron deficiency and thalassemia. In clinical practice, in some cases, differentiation of microcytic and hypochromic anemia become difficult on the basis of traditional red cell parameters. This study primarily aimed to evaluate the usefulness of red cell distribution width (RDW), immature reticulocyte fraction (IRF), and reticulocyte hemoglobin equivalent (Ret-He) in the discrimination of alpha thalassemia, beta thalassemia, and latent iron deficiency. METHODS: In this retrospective study laboratory data including complete blood counts of females diagnosed with alpha thalassemia, beta thalassemia, and latent iron deficiency were retrospectively reviewed. Receiver operating characteristic (ROC) curve was constructed to evaluate the applicability and discriminatory efficiency of RDW, IRF, and Ret-He. RESULTS: Sensitivity and specificity of RDW-CV and RDW-SD was lower in the alpha thalassemia and beta thalassemia groups. Immature reticulocyte fraction (IRF) and reticulocyte hemoglobin equivalent (Ret-He) were significantly higher in the iron deficient group as compared to alpha and beta thalassemia. CONCLUSIONS: In alpha and beta thalassemia, RDW-SD and RDW-CV were found to be poor discriminators. Sig-nificantly reduced levels of Ret-He were observed in alpha thalassemia and beta thalassemia in comparison to iron deficient group. While iron deficient group was characterized by increased values of RDW-SD, RDW-CV, IRF, and Ret-He.

Prevalence and Specificity of Red Cell Alloantibodies in Un-Transfused Multiparous Women.

BACKGROUND: Maternal alloantibodies may have devastating effects on the fetal red cells leading to hemolytic disease of the fetus and newborn (HDFN). The purpose of this study was to observe the prevalence and specificity of red cell alloantibodies in untransfused multiparous women. METHODS: This study was conducted at the Baqai Institute of Hematology, Baqai Medical University and Husaini blood bank Karachi, Pakistan. Blood samples were collected and analyzed using Bio-Rad/DiaMed reagents to determine the frequency of alloantibodies in 1,000 untransfused multiparous females (five or more than five pregnancies) from various hospitals and maternity centers of Karachi. RESULTS: In this study, red cell alloimmunization was found to be 2.8% in the studied population. Detected antibodies include anti D (28.6%), anti C (3.6%), both anti D and anti C (7.1%), anti c (3.6%), anti E (7.1%), anti K (14.3%), anti Fya (3.6%), anti M (7.1%), anti S (7.1%), anti Lea (3.6%), anti Leb (7.1%), and nonspecific cold antibodies (7.1%). CONCLUSIONS: Various clinically significant and cold type red cell alloantibodies were detected in this study. It is suggested that studies should be done from the first to the fifth pregnancy as the chances of developing alloantibodies increases with increase in parity up to the 5th gestation and it falls significantly thereafter. Antibody screening and identification of all clinically significant antibodies should be carried out during pregnancy to prevent the fatal complications of HDFN.

Revisiting Iron Metabolism, Iron Homeostasis and Iron Deficiency Anemia.

BACKGROUND: Iron deficiency anemia (IDA) is one of the commonest clinical scenarios especially in children, women of childbearing age, and elders. The crux of this review was revisiting iron homeostasis, mechanism of iron absorption, causes, laboratory diagnosis, and management of IDA. METHODS: This narrative review is compiled after a relevant literature search from electronic databases including, but not limited to, Google, Google Scholar, PMC, PubMed, Science Direct, and Scopus. The key words used for searching relevant literature include iron, iron deficiency, iron deficiency anemia, iron metabolism, hepcidin, transferrin, causes of iron deficiency anemia, and laboratory diagnosis of iron deficiency anemia. Reference hema-tology books were also consulted. RESULTS: According to the published literature, about one mg of iron is required daily which equals its loss, although the iron requirement increases in pregnancy and lactating mothers. Dietary non heme iron (oxidized Fe3+) is reduced to the ferrous (Fe2+) form by ferrireductase present in the brush border of duodenal enterocytes. Ferrous iron is absorbed in the brush border of duodenal enterocytes through a carrier protein, divalent metal transporter 1 (DMT1). Heme iron is absorbed by the duodenal enterocytes through a mechanism that is not well understood or a receptor yet to be discovered. Transferrin receptor helps in the internalization of iron in the cells. Hepcidin acts as a gatekeeper and controls iron absorption by enterocytes and macrophages. IDA may be caused by decreased intake of iron, increased iron requirements or loss of iron from the body. CONCLUSIONS: Iron deficiency anemia is the most common nutritional anemia that affects large numbers of people in developed as well as in developing countries. It is estimated that approximately 2 billion people around the world have IDA. Microcytosis with marked reduction in serum iron, decreased % saturation of transferrin, low ferritin, and reduced or even undetectable hepcidin are the laboratory features of IDA. In addition, total iron binding capacity and soluble transferrin receptors increase significantly in IDA. Management of IDA is incomplete if the underlying cause is not ruled out and left untreated.

Prevalence of ß-S Globin Haplotypes in Jazan Region of Saudi Arabia.

BACKGROUND: Sickle cell disease (SCD) is a common hematological genetic disorder in Saudi Arabia, Africa, the Mediterranean region, and India. The present study aimed to characterize ßS haplotypes found in the Jazan region, Saudi Arabia. METHODS: One hundred sickle cell trait (SCT) individuals, diagnosed during their visit to the premarital screening clinic at King Fahad Central Hospital, were included in the study. Molecular analysis was carried out by polymerase chain reaction (PCR) and six polymorphic sites of the ß-globin gene were analyzed using restriction endonucleases Hind II, Xmn-I, Hind III, and Ava II. RESULTS: The results of the current study revealed the presence of five typical haplotypes in which Benin, Bantu, and Senegal were found in homozygous state with 29%, 3% and 1% frequencies, respectively. Interestingly, 29% of the studied population showed atypical haplotypes in heterozygous state and 2% in homozygous state for the first time in Jazan region. CONCLUSIONS: In addition to the typical haplotypes, high frequency of atypical haplotypes in this study indicates a diverse genetic mechanism that might have a crucial effect on the severity of SCD in this region. Therefore, considering this study in a cohort population with SCD in Jazan region may provide more indepth details about the correlation between haplotypes and the clinical manifestation of the disease.

Prevalence of Duffy Blood Group Antigens and Phenotypes among Saudi Blood Donors in Southwestern Saudi Arabia.

BACKGROUND: Knowing the prevalence of blood group antigens in a given population is important to prevent hemolytic reactions. The Duffy blood group system (FY) has two main antigens, Fya and Fyb. Antibodies binding these antigens can cause immediate/delayed hemolytic transfusion reactions as well as hemolytic disease of the fetus and newborn. In this study, frequencies of Fya and Fyb antigen expression and FY phenotypes were determined in a cohort of Saudi blood donors. METHODS: For this study, 143 samples were collected from randomly selected volunteer Saudi blood donors living in Jazan Province. Serological analysis, using gel card technology, was performed to detect Fya and Fyb antigens among the samples. RESULTS: The frequencies of Fya and Fyb antigens were 12.58% and 11.18%, respectively. The numbers and frequencies of FY phenotypes were as follows: Fy(a+b-), 15 (10.48%); Fy(a-b+), 13 (9.10%); Fy(a+b+), 3 (2.10%), and Fy(a-b-), 112 (78.32%). The frequencies of the FY phenotypes were highly and significantly different in Jazan Saudis compared to other ethnicities (< 0.01). CONCLUSIONS: This study reports the frequencies of the Fya and Fyb antigens and phenotypes of the FY blood group system in the Kingdom of Saudi Arabia's Jazan Province. The null phenotype Fy(a-b-) was the most prevalent among this population. This study highlights the importance of investigating FY alleles in different provinces of the Kingdom of Saudi Arabia.

Frequency and genotyping of alpha thalassemia in individuals undergoing premarital screening.

OBJECTIVE: To evaluate the frequency of alpha thalassemia and detect mutations in the alpha genes in individuals undergoing premarital screening. METHODS: The cross-sectional study was conducted at King Fahad Central Hospital, Jazan, Saudi Arabia, from January 2018 to May 2019, and comprised blood samples of individuals visiting the premarital screening clinic. The samples were analyzed for complete blood counts and haemoglobin electrophoresis. Molecular analysis of samples suspected for alpha thalassemia was done using alpha-globin StripAssay kit. Data was anlaysed using SPSS 20. RESULTS: Of the 3,970 samples analysed, 1,859(46.83%) were from males and 2,111(53.17%) from females. The overall frequency of suspected alpha thalassemia was 4.43% based upon haematological parameters including complete blood count and haemoglobin electrophoresis. Overall, 80 suspected samples were selected for genetic analyses, and, of them, 76 (95%) were positive for deletional and non-deletional mutations of alpha-globin genes, while 4 (5%) were negative for any of the 21 mutations tested. CONCLUSIONS: Alpha thalassemia was found to be highly prevalent in the study area.

Undiagnosed Hemoglobinopathies: A potential threat to the premarital screening program.

OBJECTIVES: To evaluate the prevalence of undiagnosed hemoglobinopathies among individuals visiting the premarital screening Centre. METHODS: This study was conducted at Premarital Screening Centre, King Fahad Central Hospital and Research Centre, Jazan, between January 2018 and October 2018. A total of 3,970 (male n =1,859 and female n = 2,111) individuals were included in the study. Data of complete blood count, hemoglobin electrophoresis and sickling tests of all individuals recruited in the study were obtained and statistically analyzed. RESULTS: One thousand three hundred and twelve individuals had abnormal complete blood counts or hemoglobin electrophoresis results, that include sickle cell trait (13.5%), sickle cell disease (0.7%), ß thalassemia with sickle cell trait (2.46%), ß thalassemia trait (1.51%), ß thalassemia major (0.075%), suspected α thalassemia or other hemoglobinopathies (4.43%), hemoglobin H (0.3%), hemoglobin E (0.075%), undiagnosed cases (0.91%) and iron deficient (7.23%). CONCLUSION: A high percentage of individuals are suspected for α thalassemia or other hemoglobinopathies that needs to be diagnosed. Further investigations shall be included in the premarital screening program to diagnose these inconclusive cases. Coexistence iron deficiency with thalassemia shall also be ruled out during premarital screening program.

Pre and post apheresis platelet CD markers evaluation using flow cytometry.

OBJECTIVE: To evaluate the effect of apheresis procedure on platelet's activation dependent glycoproteins' expression on their surface. METHODS: This study was conducted between June 2012 and June 2014, and comprised blood and platelet samples. Two samples were collected i.e. venous blood sample and apheresed platelet sample from the same donor. Platelet cluster of differentiation markers (41, 61, 62p and 63) were analysed within 2 hours of sample collection using flow cytometry. SPSS 20 was used for data analysis. RESULTS: A total of 100 donors were recruited in this study. Cluster of differentiation (CD) markers' expression of 100 pre-apheresis and 100 platelet apheresis samples was compared after the completion of platelet apheresis procedure. CD 41 and 61 showed no significant difference between pre- and post-apheresis platelets; (p=0.447 and 0.712, respectively). CD 62p positivity of pre-apheresis platelets (9.57±5.88%), and post-apheresis platelets (55.57±24.59%) showed statistically highly significant difference (p<0.001). CD 63 expression of pre- and post-apheresis platelets was 14.19±11.84% and 40.77±16.08%, respectively (p=0.04). Moderate correlation existed between post-apheresis platelets' CD 62p and 63 (r=0.62).. CONCLUSIONS: Platelet CD markers 41 and 61 did not show any change in pre- and post-apheresis samples while expression of 62p and 63 increased during the apheresis.

Disorders associated with malabsorption of iron: A critical review.

Malabsorption is a disorder of the gastrointestinal tract that leads to defective digestion, absorption and transport of important nutrients across the intestinal wall. Small intestine is the major site where most of the nutrients are absorbed. There are three main mechanisms of malabsorption; premucosal, mucosal and postmucosal. Premucosal malabsorption is the inadequate digestion due to improper mixing of gastrointestinal enzymes and bile with chyme. This could be because of surgical resection of the small intestine or a congenital deficiency of the enzymes and bile responsible for digestion e.g. postgastrectomy, chronic pancreatitis, pancreatic cancer, cystic fibrosis, gallstones, cholangitis etc. Mucosal malabsorption occurs in celiac disease, tropical sprue, Crohn's disease etc. Postmucosal condition arises due to impaired nutrients transport e.g. intestinal lymphangiectasia, macroglobulinemia etc. Disorders of malabsorption lead to decreased iron absorption and produce iron deficiency anemia. Using the index terms malabsorption, postgastrectomy, chronic pancreatitis, pancreatic cancer, cystic fibrosis, gallstones, cholangitis, celiac disease, tropical sprue, Crohn's disease intestinal lymphangiectasia, macroglobulinemia and iron deficiency anemia the MEDLINE and EMBASE databases were searched. Additional data sources included bibliographies and references of identified articles.

Comparative analysis of serum iron, serum ferritin and red cell folate levels among breast fed, fortified milk and cow's milk fed infants.

OBJECTIVE: Iron and folic acid are essential nutrients needed for hematopoiesis. Infants' diet is commonly deficient in these micronutrients that lead to nutritional anemia. Aim of this study was to determine serum iron, serum ferritin and red cell folate levels among healthy breast fed, fortified milk and cow's milk fed infants. METHODS: A total of 120 infants of 4-9 months of age were enrolled in this study. It included 40 normal breast fed controls, 40 fortified milk fed (FM) and 40 cow's milk fed (CM) infants. Serum iron, serum ferritin and red cell folate concentrations were determined using colorimetric and enzyme immunoassay techniques. RESULTS: Mean serum iron, serum ferritin and red cell folate concentrations of breast fed control group were 120.9±68.4µg/dl, 109±71.7ng/ml and 1044.1±409.2ng/ml respectively. Fortified milk (FM) group showed significantly decreased serum iron (p<0.003) as compared with controls whereas serum ferritin and red cell folate values showed insignificant change (p=0.25 and p=0.85 respectively). However serum iron, serum ferritin and red cell folate were significantly decreased in cow's milk fed (CM) group as compared with control subjects (p<0.04, p<0.006, p<0.02 respectively). Comparison of these biochemical parameters between FM and CM groups showed statistically significant difference of serum ferritin and red cell folate among cow's milk group (p<0.0001 and p<0.02) whereas serum iron level showed no significant difference, a p-value being 0.38. CONCLUSION: Healthy breast fed infants do not need any supplementation and fortification of iron and folic acid. Fortified milk appears to be an acceptable alternative in the absence of breast milk whereas cow's milk is a poor source of iron and folic acid in infants.

Cytogenetic and Molecular Analyses of Philadelphia Chromosome Variants in CML (chronic myeloid leukemia) Patients from Sindh using Karyotyping and RT-PCR.

OBJECTIVE: To determine the frequency of Philadelphia chromosome (Ph) and its variants in chronic myeloid leukemia (CML) cases at a tertiary care hospital of Sindh. METHODS: The study was conducted at the Department of Pathology, Liaquat University of Medical and Health Sciences, Jamshoro and Isra University Hospital, Hyderabad during May-to-September 2014. Bone marrow and peripheral blood samples from a total of 145 diagnosed cases of CML were collected. Cytogenetic analyses were performed using karyotyping as per the International System for Human Cytogenetic Nomenclature guidelines. All karyotypic images were analyzed using the Cytovision software. In order to identify BCR-ABL transcripts, RT-PCR was performed. Statistical analysis of the data was done using SPSS-version-21.0. RESULTS: Of the 145 samples, a total of 133 (91.7%) were positive for the Ph (Ph+) while 12 (8.3%) were negative for the Ph (Ph-). Of the 133 Ph+ samples, standard karyotypes were noted in 121 (91%), simple variants in 9 (6.7%) and complex variants in 3 (2.3%) of the samples. All the Ph+ samples (n=133) showed BCR-ABL positivity. Of the 12 Ph- samples, a total of 7 (58.3%) were BCR-ABL-positive and 5 (41.6%) were BCR-ABL-negative. CONCLUSION: Frequency of the Ph was found to be of 90.9% in CML patients using a highly sensitive technique, the RT-PCR. Cytogenetic abnormalities were at a lower frequency. Cytogenetic and molecular studies must be conducted for better management of CML cases. These findings could be very useful in guiding the appropriate therapeutic options for CML patients.

Malabsorption of iron as a cause of iron deficiency anemia in postmenopausal women.

OBJECTIVE: Malabsorption is one of the causes of iron deficiency anemia in postmenopausal women. The main objective of this study was to access the frequency of malabsorption in iron deficient anemic postmenopausal women. METHODS: A total of 123 postmenopausal women were enrolled in the study. Of these 123 women, 50 were included as 'control group' and 73 patients with comparable severity of anemia were the 'patient group'. Two tablets of ferrous sulfate (200 mg/tablet) along with one tablet of vitamin C (500 mg) were given to all participants. Serum iron levels were determined on samples collected from all participants before and after the administration of ferrous sulfate. Difference between before and after serum iron levels of normal and patients were compared. RESULTS: No change in serum iron between sample one and sample two represented malabsorption. Out of 73, 5 postmenopausal anemic patients showed no change in their serum iron level after the administration of ferrous sulfate. This study shows that frequency of malabsorption of iron in postmenopausal women is 6.8%. CONCLUSION: Malabsorption should be considered as a prevalent cause of iron deficiency anemia in postmenopausal women. It should be properly diagnosed and iron response should be monitored properly in postmenopausal women with IDA after oral iron therapy. If a postmenopausal woman does not show any response to oral iron therapy, she should be evaluated for iron loss (blood loss and/or malabsorption). Intravenous route should be used for the administration of iron in these patients.

Functional status of vascular endothelium in diabetes mellitus.

Normal endothelial cells synthesize and release biologically active substances. These substances maintain homeostasis through adequate blood flow, delivery of nutrients, activation and inhibition of coagulation proteins, prevention of thrombosis and diapedesis of leukocyte. Endothelial dysfunction implies failure of vascular endothelium to perform its normal functions of vasodilatation and vasoconstriction. It results from an imbalance between endothelium derived constricting and relaxing factors. Altered endothelial cell activity predisposes to increased production of vasoconstrictors, i.e., prostaglandins, endothelins, glycated proteins, endothelial adhesion molecules and platelet and vascular growth factors. These changes enhance vasomotor tone, vascular permeability, growth and remodeling of the vessels. Diabetes is associated with abnormalities of vascular endothelium. Several regulatory vasodilators and vasoconstrictors are altered in diabetes leading to diabetic vascular complications. Balance between dilating and constricting substances is altered and is shifted towards vasoconstriction in diabetes. Disturbances in the endothelial functions lead to increased platelet adhesion and aggregation in patients with diabetes. Activated platelets interact with endothelial cells and leukocytes in the genesis of atherosclerosis. High level of Von Willebrand factor (vWF) is a consistent finding in diabetes. Increased vWF level is one of the major risk factors for the development of micro vascular complications. High levels of vWF may predict cardiovascular disease progression in diabetes mellitus.

Frequency of ABH secretors and non secretors: A cross sectional study in Karachi.

OBJECTIVE: ABO blood group and secretor status is valuable in relation to some diseases in clinical and forensic medicine. Across the globe there are geographic and racial differences in the frequency of secretors and non-secretors. Aim of this study was to evaluate the status of ABH blood group secretors and non-secretors in Karachi (Pakistan). METHODS: Blood and saliva samples were randomly collected from one hundred and one (n=101) healthy adult students (76 male, 25 female) ranging in age from 15 to 40 years. Their ABO and Rhesus blood groups were determined by conventional methods, and their secretor status was studied by hemagglutination inhibition method of saliva. RESULTS: RESULTS showed that 64.4% of the study population were ABH blood group secretors while 35.6% were non-secretors. Frequencies of the secretor status among various ABO blood groups were 71.4% in group A, 79.5% in group B, 45.5% in group AB, and 61.5% in group O. CONCLUSION: Frequency of ABH secretor is high (64.4%). Blood group B has the highest secretor (79.5%) frequency while Blood group AB has the lowest (45.5%).

Erythroferrone in focus: emerging perspectives in iron metabolism and hematopathologies.

Beyond its core role in iron metabolism, erythroferrone (ERFE) has emerged as a key player with far-reaching implications in various hematologic disorders. Its regulatory effect on hepcidin underlines its significance in conditions characterized by disrupted iron homeostasis. In ß-thalassemia and myelodysplastic syndromes, its dysregulation intricately contributes to the clinical challenges of anemia and iron overload which highlights its potential as a therapeutic target. In anemia of chronic disease and iron deficiency anemia, ERFE presents a unique profile. In chronic kidney disease (CKD), the intricate interplay between ERFE, erythropoietin, and hepcidin undergoes dysregulation, contributing to the complex iron imbalance characteristic of this condition. Recent research suggests that ERFE plays a multifaceted role in restoring iron balance in CKD, beyond simply suppressing hepcidin production. The potential to modulate ERFE activity offers a novel approach to treating a spectrum of disorders associated with iron dysregulation. As our understanding of ERFE continues to evolve, it is poised to become a key focus in the development of targeted treatments, making it an exciting and dynamic area of ongoing research. Modulating ERFE activity presents a groundbreaking approach to treat iron dysregulation in conditions like iron deficiency anemia, thalassemia, and hemochromatosis. As new research unveils its intricate roles, ERFE has rapidly emerged as a key target for developing targeted therapies like ERFE agonists and antagonists. With promising studies underway, this dynamic field holds immense potential to improve patient outcomes, reduce complications, and offer personalized treatment options in hematology research. This comprehensive overview of ERFE's role across various conditions underscores its pivotal function in iron metabolism and associated pathologies.

Exploring antithrombin: insights into its physiological features, clinical implications and analytical techniques.

Antithrombin is an essential protein that acts as a natural anticoagulant in the human body. It is synthesized by the liver and belongs to the serine protease inhibitors, which are commonly referred to as the SERPINS superfamily. The antithrombin molecule comprises 432 amino acids and has a molecular weight of approximately 58 200 D. It consists of three domains, including an amino-terminal domain, a carbohydrate-rich domain, and a carboxyl-terminal domain. The amino-terminal domain binds with heparin, whereas the carboxyl-terminal domain binds with serine protease. Antithrombin is a crucial natural anticoagulant that contributes approximately 60-80% of plasma anticoagulant activities in the human body. Moreover, antithrombin has anti-inflammatory effects that can be divided into coagulation-dependent and coagulation-independent effects. Furthermore, it exhibits antitumor activity and possesses a broad range of antiviral properties. Inherited type I antithrombin deficiency is a quantitative disorder that is characterized by low antithrombin activity due to low plasma levels. On the other hand, inherited type II antithrombin deficiency is a qualitative disorder that is characterized by defects in the antithrombin molecule. Acquired antithrombin deficiencies are more common than hereditary deficiencies and are associated with various clinical conditions due to reduced synthesis, increased loss, or enhanced consumption. The purpose of this review was to provide an update on the structure, functions, clinical implications, and methods of detection of antithrombin.

Retinoblastoma: An update on genetic origin, classification, conventional to next-generation treatment strategies.

The most prevalent paediatric vision-threatening medical condition, retinoblastoma (RB), has been a global concern for a long time. Several conventional therapies, such as systemic chemotherapy and focal therapy, have been used for curative purposes; however, the search for tumour eradication with the least impact on surrounding tissues is still ongoing. This review focuses on the genetic origin, classification, conventional treatment modalities, and their combination with nano-scale delivery systems for active tumour targeting. In addition, the review also delves into ongoing clinical trials and patents, as well as emerging therapies such as gene therapy and immunotherapy for the treatment of RB. Understanding the role of genetics in the development of RB has refined its treatment strategy according to the genetic type. New approaches such as nanostructured drug delivery systems, galenic preparations, nutlin-3a, histone deacetylase inhibitors, N-MYC inhibitors, pentoxifylline, immunotherapy, gene therapy, etc. discussed in this review, have the potential to circumvent the limitations of conventional therapies and improve treatment outcomes for RB. In summary, this review highlights the importance and need for novel approaches as alternative therapies that would ultimately displace the shortcomings associated with conventional therapies and reduce the enucleation rate, thereby preserving global vision in the affected paediatric population.