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Introduction: Leukocytes causing a wide variety of side effects after transfusion are present in all blood products prepared by standard methods. As a consequence, the use of filter technology for leukoreduction has been widely practiced .According to AABB accreditation in 1996, leukoreduced blood components must contain less than 5×106 leukocytes per unit, but sometimes this value is higher even in leukoreduced products. In this study we did absolute leukocyte count in filtered (home made bedside filter) packed cell units by two methods of true count as standard method and CD45 MoAb.

Materials & Methods: 93 packed cell units were stored at 4°c and filtered by two types of home-made filters according to manufacturer's instructions. Furthermore, eight packed cell units were filtered by Europe certified control group filters (bio-fil). Sample preparation was done according to True count kit and CD45 MoAb procedures and analysis was performed by flowcytometry (EPICS-XL,coulter) and (Partec PAS III).The results were then analyzed by chi2 test via SPSS.

Results: The mean values of leukocyte count/unit by anti CD45 and True count method were 9×106 and 10×106 respectively in 55 pre-revised filter bags these figures were 4.2×106 and 4.8×106 in 30 post-revised filters, whereas the mean leukocyte count/bag in eight control filters was 2.3×106,we selected randomly eight test units out of 53 and 30 pre-revised and post-revised filtered bags, respectively(equal with number of units in the control group) to compare the test and control groups The mean values of leukocyte count/bag in pre-revised test group was 7.9±5.4×106 and in postrevised test group was 4.2 ×106 but in the control group it was 2.3 ×106 (p value<0.05).

Discussion: According to the results, the mean leukocyte count/bag in pre-revised group was higher than AABB standard. 38.2 % of bags had lower and 61.8 % had higher leukocyte count than the standard value (48.9 to 74.6 % with CI=95 %), this indicates the necessity of revision in product technology of homemade filters. relevant manufacturer revised the product technology and material accordingly, so that new filters (post-revised group) reduced leukocytes within standard limits (leukocyte count in 6 bags were out of standard range).In post-revise filter group, 20 % had a leukocyte count of more than 5×106 while 80% showed less than this value (5.7%-34.3% with CI=95%).There is a significant difference between control and pre-revised test groups (p=0.03).In post-revised test group, despite significant differences, the mean values of leukocyte count/bag were within normal standard range. The results of this research caused home-made filter production with higher quality.

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Background: Hepatitis C virus (HCV) infection is the most common transfusion transmitted disease in poly-transfused patients worldwide. In this study we aimed to evaluate the effects of pegylated interferon alfa-2a (PEG-IFN A-2a) in reducing serum ALT and eradicating serum hepatitis C virus (HCV) RNA in HCV infected polytransfused thalassemic patients.

Materials and Methods: A cohort of 51 HCV-RNA positive thalassemic patients were enrolled to our study and received 180 µg PEG-IFN A-2a once-weekly for 48 weeks. The primary end point was sustained virological response (SVR). The secondary outcome was normalization of ALT. Patient safety was assured by monthly, and if needed, weekly laboratory assessment and visits.

Results: Of 52 patients, 42 participants completed the treatment schedule. A sustained virological response (SVR) was attained in 22/51 (43%) cases. Among non-responders or relapsers to previous HCV antiviral therapy, 9/27 (33%) attained an SVR. Five patients died during treatment and 3 subjects discontinued the therapy because of adverse effects. Adverse events were generally mild, and laboratory abnormalities were rare.

Conclusion: A course of 48-week PEG-IFN A-2a monotherapy is effective in eradicating HCV-RNA during treatment. But about one third of thalassemic patients would relapse within 6 months of treatment schedule completion, in whom combination therapy is needed.

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Background: Human leukocyte antigens (HLA) are polymorphic cell surface proteins. Distribution of HLA alleles vary among different racial and ethnic populations in unrelated stem cell registries. Determination of HLA allele frequencies in different ethnic groups is useful for population genetic analyses. Materials and Methods: Based on data available from the Iranian Stem Cell Donor Registry, HLA-A, B, DRB1 allele frequencies were evaluated from 244 individuals who were recruited as unrelated volunteer donors by PCR-SSP method in people of Fars ethnicity living in Tehran, Iran. Results: The most frequent alleles found were HLA-A*02(19.8%), HLA-A*03(13%), HLA-A*11 and -24 (12.5%), HLA-B*35(17.7%) HLA-B*51(13.2%), HLA-DRB1*11(20.8%), whereas HLA-A*34 and HLA-A*44 (0.2%), HLA-B*47, B*54, B*56, B*73(0.2%), and HLA-DRB1*09 (0.4%) were the least frequent alleles. Conclusion: Identifying HLA allele frequencies in different ethnic groups, helps in designing a better plan for development of donor centers in different provinces of a country, and a more precise prediction of donor size in the registry, in addition to finding suitable donors for patients in need of hematopoietic stem cell transplantation. Keywords: HLA, unrelated donors, ethnic groups, Iran

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Background: Transfusion is the mainstay treatment of patients with thalassemia major and occasionally in thalassemia intermediate. Alloimmunization is an unwanted side effect of blood transfusion. The present study intended to determine the frequency of alloimmunization in patients with β- thalassemia major and thalassemia intermediate in Southwest Iran. Patients and Methods: This was a cross-sectional study on 133 transfusion dependent β-thalassemia patients at Shafa hospital-in Southwest Iran. The method of antibody screening was the tube method. All panel test phases were done at immunohematology laboratory of Iranian Blood Transfusion Organization. Results: There were 66 males (49.1%) and 67 females (50.9%) with the mean age of 17.5 years (SD±7.5) included in this study. The antibody screening panel test was positive in 42 patients (32.06%). Twenty five patients (18.7%) had alloantibody and 17 patients (12.7%) also had autoantibody. The predominant pattern of alloimmunization was alloantibodies against RH sub groups system in 55 percent of patients and 33% of patients had alloantibodies against Kell system. Three important factors that significantly influenced the frequency of alloimmunization were: age at the first blood transfusion, splenectomy and β- thalassemia intermediate. Conclusion: Alloimmunization is a common complication among patients with transfusion dependent β-thalassemia in Khuzestan province, Iran. Matching the selected donors with recipients based on the extended red blood cell antigen typing may decrease the incidence of alloimmunization. Key Words: Alloimmunization, thalassemia major, thalassemia intermediate, RH blood group, Kell blood group.

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Background: Hemophilia B is an X-linked hereditary disorder of blood coagulation system which is caused by factor IX (FIX) deficiency. Factor IX is a plasma glycoprotein that participates in the coagulation process leading to the generation of fibrin. Replacement of factor IX with plasma-derived or recombinant factor IX is the conventional treatment for hemophilia B to raise the factor IX level to therapeutic range. Recently, gene therapy has been regarded as a promising approach to treat hemophilia B. This study was aimed to express the factor IX in human amniotic membrane-derived mesenchymal stem cells (hAM-MSCs). Materials and Methods: Human amniotic membrane-derived mesenchymal stem cells were isolated and characterized from amnion membrane. Factor IX from commercially available plasmid was sub-cloned into pcDNA3.1 vector. Recombinant pcDNA3.1-FIX construct was confirmed by PCR, enzymatic digestion and DNA sequencing. Mesenchymal stem cells were transfected with the recombinant vector. Expression of factor IX was determined by RT-PCR, ELISA and its biological activity assay was performed using aPTT. Results: Isolated hAM-MSCs expressed specific mesenchymal stem cells markers and were able to differentiate to osteocytes and adipocytes lineages. hAM-MSCs expressed hrFIX at mRNA and protein level. The maximum amount of hrFIX was 120 ng/ml at 72 hrs after hAM-MSCs transfection. This hrFIX was biologically active (11% activity), formed fibrin clot in aPTT test and caused more than two fold decrease in clotting time. Conclusion: The hAM-MSCs expressing factor IX would be useful for gene therapy of hemophilia B. However further studies are required to prove these finding. Key words: Hemophilia B, amnion membrane, mesenchymal stem cell, factor IX, gene therapy.

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Background: Beta thalassemia gene mutations are among common mutations in southwest Iran. However, Hemoglobin E (Hb E) and Hb E/β⁰ thalassemia account for a small number of hemoglobinopathies in Iran. This is the first study to directly address the existence of Hb E and consequently Hb E/β⁰ thalassemia in southwest Iran. Methods: This retrospective study discovered seven cases of Hb E/β⁰ thalassemia among 700 patients with hemoglobinopathies referring to Health Institute and Research Center for Thalassemia and Hemoglobinopathy in southwest Iran. EDTA and clot blood samples were obtained and analyzed for complete blood counts, hemoglobin electrophoresis, LDH, bilirubin, ferritin and amplification refractory mutation system (ARMS) technique by polymerase chain reaction (PCR) and DNA sequencing. Results: Out of 700 cases, seven patients with Hb E/β⁰ thalassemia were detected (1%). Four patients were classified into non-transfused dependent Hb E/β⁰ thalassemia and three cases were classified into transfusion dependent Hb E/β⁰ thalassemia group. Alpha thalassemia (deletional and non-deletional) and XmnI gene polymorphism were not found in either of cases. Conclusion: Hb E/β Thalassemia is not a common hemoglobin disorder in southwest Iran. Phenotype heterogeneity is common in Iranian patients from a mild asymptomatic anemia to severe anemia that can be presented in the early years of life. This was the first report of Hb E/β⁰ thalassemia from Iran. Keywords: Hb E/β⁰ Thalassemia, Southwest Iran, Transfusion dependent, Non-transfusion dependent, Hb E mutation.

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Autoimmune lymphoproliferative Syndrome (ALPS) is a rare inherited disorder of apoptosis. It usually presents with chronic lymphadenopathy, splenomegaly, and symptomatic cytopenia in a child. Herein, we report a 14-year-old boy with symptoms misdiagnosed as hemophagocytic lymphohistiocytosis who was treated before ALPS was diagnosed for the patient. This case should alert pediatricians to consider ALPS in differential diagnosis of a child with lymphadenopathy, splenomegaly, and cytopenia.

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Background: Considering the increasing number of patients with hemophilia and infrastructure requirements for a comprehensive approach, development of a recombinant factor has become a milestone. The objective of this study was to assess the safety, efficacy and non inferiority of Safacto (Recombinant factor VIII) compared with plasma-derived factor in the treatment of hemophilia A. Methods: 10 patients with severe hemophilia A were enrolled in this study. Each patient was treated by a 40-50 IU/kg infusion of either plasma derived or recombinant factor VIII after initiation of each of 4 consecutive hemarthrosis episodes in a triple-blind prospective crossover permuted block randomizing method. Clinical efficacy scale score and in vivo recovery of factor VIII was assessed in each of the treated bleeding episodes. Any adverse event was also recorded. Results: The mean±SD level of factor VIII in the plasma versus recombinant groups was 111.5±39 and 115±39, respectively without any significant difference. Response scaling method which assessed pain and range of motion revealed equalized scores along with in vivo recovery, hence treatment success rate was comparable in both groups. One non-recurring, mild skin rash reaction occurred simultaneous with the administration of plasma derived factor. Conclusion: Safacto (r-FVIII) is safe and effective and non-inferior to plasma derived factor VIII in the treatment of hemophilia A related bleeding events.

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Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most known enzyme defects in Iran with various genetic mutations. We aimed to study the predisposing factors of hemolysis in children with G6PD deficiency.
Methods: This study was done during 2007-2012 in two referral centers of Mofid Children’s Hospital and Baqiyatallah Hospital, Tehran, Iran. The hospital records of the patients were fully reviewed and questionnaires for each patient were filled for the date of admission, initial symptoms, initial laboratory results, family history and history of any drug consumption, infection or fava bean ingestion. 
Results: Medical records of 192 children with mean age of 4.2 years (1 month to 14 years) were extracted. 68.2% of the cases were male. Hemolytic crises were significantly more common in spring which is the peak time for fava bean consumption and occurred more frequently in those with a family history of G6PD deficiency especially in females. The most common initial symptoms were jaundice (71%), dark color urine (49%), fever (34.4%), and pallor (24.5%), followed by abdominal pain (16.7%). Fava bean intake (93%) was the first etiological agent triggering hemolysis followed by infectious agents and drug consumption. Initial hemoglobin level was significantly lower in male patients.
Conclusion: Regarding the high prevalence of G6PD deficiency in Iran, we should emphasize on education of parents and physicians about the disease and prevention of fava bean ingestion in people with G6PD deficiency.

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Macrophage activation syndrome (MAS) is a rare feature of rheumatic disorders in children and adolescence and its presentation as the first symptom of rheumatic disorders is very infrequent.
A 9-year-old girl, in whom MAS developed, was admitted to our Hospital in Tehran, Iran. She suffered from high grade fever and rash followed by multiple joint swelling months afterwards. Bone marrow aspiration and biopsy showed normocellular marrow with a cellularity of 90%. Benign-looking macrophages were remarkably increased; many of them showed hemophagocytic features. According to the presentation of long-standing fever and observation of “hemophagocytic macrophage” in bone marrow, MAS was diagnosed for the patient. Additionally, due to recurrent joint swelling in following months, she was diagnosed to be affected by “Juvenile Idiopathic Arhtritis” complicated by MAS.
MAS is a rare complication of rheumatic disorders which should be considered as the first presentation of rheumatic disorders in children specifically in those presenting with high fever, hepatosplenomegaly, lymphadenopathy and severe cytopenia. 

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Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease with diverse clinical manifestations involving multiple organ systems. Peritoneal involvement as a sign of gastrointestinal disease in SLE is a rare condition. Massive ascites as the initial manifestation of SLE is an extremely rare situation. Here, we report a 13-year-old female with bile-stained vomiting, ascites and signs of pseudo-obstructions with a past medical history of immune thrombocytopenic purpura (ITP) who was later diagnosed to have SLE.

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Background: Coronavirus disease 2019 (abbreviated as COVID-19) is a mysterious respiratory syndrome symptomatically spanning from healthy carriers to patients with life-threatening complications, in some cases, leading to a mournful death. For the time being, the contributory role of hematologists is much more recognized in the management of COVID-19, since the emergence of coagulopathy has recently been the focus of many studies in SARS-CoV-2 infection. 
Methods: To provide a well-conceptualized viewpoint demonstrating the prognostic value of coagulation-related laboratory tests, we planned to perform a meta-analysis of pertinent literature representing information on PT, aPTT, and D-dimer tests in patients with COVID-19. 
Results: Albeit the estimated pooled means of PT and aPTT were higher in severe cases, their mean values were not significantly higher as compared with patients in a non-severe condition. On the other hand, the mean value of D-dimer in severe patients was significantly higher than non-severe cases (X2=6.34, P=0.01), highlighting that the elevation of this parameter may be associated with the progression of the disease toward an unfavorable clinical outcome. 
Conclusion: Even though at the time of writing this article the lack of adequate and appropriate studies denotes a major limitation to the current study, planning for the future research to determine the prognostic value of laboratory tests reflecting SARS-CoV-2-induced coagulopathy, mainly D-dimer, will definitively cast a flash of light on the significance of therapeutic anticoagulation at least for those with no absolute contraindication.

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Background: Although by comparing the number of deaths to the total number of cases one may conclude that most of the infected cases are recovering, taking a look at the increasing statistics of deaths shows that SARS-CoV-2 continues to take its toll. Since lymphocytes are the main immune cells battling with rapidly evolving viruses, it comes as no surprise to assume that a decreased number of these propitious soldiers may contribute to poor prognosis of the wide range of viral infections, including COVID-19. 
Methods: To provide a better prospect representing the prognostic value of lymphopenia in COVID-19, we searched the national library of medicine Medline/PubMed and performed a meta-analysis of pertinent literature representing information on the lymphocyte count in COVID-19 patients. 
Results: The results of our meta-analysis revealed that the number of lymphocytes retains a specific clinical and biological significance in this infection and lymphopenia is seemingly an important hematological abnormality that contributes to mirror the evolution toward an unfavorable outcome. 
Conclusion: The rapidly evolving nature of COVID-19 together with relentless disclosure of novel findings denotes a major limitation to the current study, and further investigations in the field of prognostic biomarkers will definitively pave the way to better manage patients with severe COVID-19. 

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Background: Educational evaluation is a broad concept that is related to all elements of the educational system. This concept is the result of the interaction of all values that are implemented with different titles and forms inside and outside the educational system to increase the performance of the educational system. The field of pediatric hematology and oncology is one that is constantly evolving due to extensive and numerous researches in various fields. These changes must be in line with changes in the health care delivery system. In this study, among the decision models, the CIPP model which is an evaluation model for curriculum evaluation given by Stufflebeam in 1983 which includes four elements: C- Context, I- Input, P- Process and P- Product., was selected to evaluate the educational curriculum of Iranian pediatric hematology and oncology fellowship.
Methods: The present study has two quantitative and qualitative aspects and a quantitative cross-sectional, descriptive-analytical study. This analysis was conducted in 2021 by the strategic group of the Iranian pediatric hematology and oncology association. Its statistical population consisted of members of this association. Most members have a degree in pediatric hematology and oncology. The research was conducted by census method. Data were collected using a researcher-made questionnaire. In general, the training course was examined in 4 areas of education and research, hardware facilities of the training and current environment, and professional abilities other than the content of the course. The efficacy of the evaluation questionnaire of the Pediatric hematology and oncology fellowship course was a combination of open and closed questions based on the “Kirk Patrick evaluation model”. This questionnaire had 20 questions. The internal evaluation based on Cronbach’s alpha was 0.92. The items surveyed in the questionnaire were: learning modern medical principles such as evidence-based medicine and clinical reasoning, learning the principles of medical ethics, study skills, understanding of legal procedures, ability to electronically research and adequacy of educational subjects. Satisfaction of the faculty members, students ‘satisfaction and the need for supplementary courses, the current method of evaluating students’ communication skills, the scientific ability of the eligible faculty in teaching current topics and participation in educating the students were among the other items of the questionnaire.
Results: In the internal validity study, Cronbach’s alpha coefficient of 0.92 was obtained for the current situation and 0.96 for the optimal situation. Descriptive statistics (mean and standard deviation) and one-group and independent t-test were used to analyze the data. Findings indicated that there was a significant difference between the current and desired status of free and absentee university exams in the areas of purpose, design, implementation, modification and feedback and the three components of each of these axes. According to the obtained results, changing the current educational curriculum of the subspecialty fellowship in pediatric blood and cancer is necessary and inevitable.
Conclusion: Corrective suggestions for writing a new curriculum in accordance with modern sciences and medical needs of the country were extracted and applied in the new curriculum.

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Several studies have demonstrated the undeniable value of plasma as the source of myriads of proteins with numerous biological activities, many of which might not be discovered yet. Plasma fractionation is a process aiming at the production of plasma-derived medicinal products (PDMPs) such as gamma globulins (immunoglobulin [Ig]), hyperimmune serum globulins, albumin, and clotting and coagulation factors like Factor VIII (FVIII) and FIX. Despite several challenges in the evolution of the plasma industry, there is still worldwide increasing demand for PDMPs with the proof that the market size value of this industry is estimated at 28.69 billion dollars in 2021. In Iran, the plasma industry began its journey with the initial activities of the Iranian Blood Transfusion Organization (IBTO). Regarding the expense of establishing companies for plasma fractionation and elevating demands of PDMP in Iran’s health system, decision-makers implemented contract fractionation which not only supply the needs of the country but also cause significant savings in financial resources. Although the amount of collected plasma has been raised, more than 400,000 liters of collected plasma is still half of the required amount as Iran’s demand for FVIII and albumin is over the supply. Putting together these data that the clinical indications for PDMPs, particularly IVIg, are growing (as seen in COVID-19) and commercially purchasing products is not economically beneficial, it is necessary for Iran’s policymakers to invest in the plasma industry by establishing more plasmapheresis centers and raising people’s awareness to donate more amount of plasma in order to elevate the levels of plasma collection annually. Moreover, entering the industry of fractionation by localization of this science and construction of fractionation plants should be on the agenda.

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Severe congenital neutropenias (SCNs) are the rare heterogenous group of preleukemia bone marrow failure syndromes characterized by impaired differentiation of neutrophilic granulocytes and, as a result, severe chronic neutropenia. Patients with SCN are predisposed to recurrent, often life-threatening bacterial and/or fungal infections beginning in the first months of life. Molecular abnormalities in 10 genes have been identified that are responsible for SCNs. The pathophysiological mechanisms of SCNs are the subject of extensive investigation and are not fully known. The current review aims to summarize the studies exploring the biological role of SCN-associated genes and the effects of mutant genes in neutropenia pathogenesis. We mainly focus on the genetic mutations that lead to SCN1 to SCN9 and X-linked SCN (XSCN) to shed more light on the pathophysiology of these diseases.

 

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Chat generative pre-trained transformer (GPT) is a large language model (LLM) artificial intelligence (AI). Indeed, ChatGPT is a chatbot able to participate in a conversation by pretending to be a human. ChatGPT is able to write convincing academic texts which are hard to be distinguished from a human-written manuscript. In the medical context, ChatGPT demonstrated its ability to write abstracts and texts related to the given questions. It could answer medical questions whether they are asked by students or researchers. ChatGPT is able to enhance the knowledge of students by designing tests and answering personalized questions, consequently reducing the burden on teachers. This AI system can participate in healthcare programs by providing information for patients and acting as the connector between patients and healthcare providers. Also, it could serve as a translator and a text generator for patients who speak a different language or those who have speech difficulties. ChatGPT is also able to provide and categorize medical information necessary for healthcare providers and physicians. Nonetheless, the major concern is the level of reliability of generated data. In some cases, ChatGPT produced misleading information and fake citations which warned medical researchers. Worryingly, these false data could distract the process of treatments and or the projects of medical researchers. Regarding the inevitable necessity of AI utilization in the medical field, strict criteria should be enforced in order to improve the efficacy and reduce the safety of the application of any AI chatbot like ChatGPT.
 

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Introduction: The role of Plasma-Derived Medicinal Products (PDMPs) in managing life-threatening diseases is remarkable. Human plasma as a raw material for PDMPs is obtained from volunteers through apheresis or whole blood collection. The global PDMPs market in 2021 shows an average annual growth rate of 7.4% since 1996 which is higher than the average annual pharmaceutical market growth rate. In line with WHO policies, Iran has improved its national voluntary non-remunerated donors (VNRD) program to supply the local PDMPs market. This study shows the 10-year Iran PDMPs market evolution to assess its self-sufficiency.
Method: We conducted a cross-sectional study from 2012 to 2021 to assess the self-sufficiency rate of Iran’s plasma industry for PDMPs including Albumin, Immune globulins, and Antihemophilic Factors. In addition, we show the gap between market supply and demand to lighten the self-sufficiency future.
Result: The annual growth rate of total collected plasma was 18.9% over 10 years in Iran from 2012 to 2021. Although the consumption rate of intravenous Immune globulins has increased from 777 kg to 2,108 Kg, due to a significant increase in local plasma production, its self-sufficiency rate increased from 53% to 93%.  Similarly, the demand rate for Albumin grew from 21% in 2012 to 90% in 2021.
Discussion: Although local plasma production in Iran significantly provided plasma self-sufficiency as a raw material, local market demand for PDMPs is mainly supplied through contract fractionation with European fractionators.  Access to complete self-sufficiency in Iran needs increasing plasma production, as well as developing major local plasma fractionators.