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BCR-ABL positive T cell Acute Lymphoblastic Leukemia (T-ALL): Exploring A Rare Case with A Comprehensive Review 2 2 CD4+/CD8+ double-positive (DP) thymocytes are normal cells within the thymus. However, the presence of mature DP T cells is indicative of cancer and abnormality in peripheral blood. Philadelphia+ (Ph+) T-ALL is extremely rare, but it holds significant therapeutic and prognostic implications. The incidence and outcomes of BCR-ABL+ T-ALL remain uncertain, and distinguishing it from T-cell lymphoblastic crises of CML can be challenging. The current document discussed a rare case of CD4+/CD8+ BCR-ABL+ T-ALL in an 11-year-old Iranian male, detailing his medical conditions, laboratory findings, and treatment. The patient presented with enlarged lymph nodes, splenomegaly, anemia, leukocytosis, and severe thrombocytopenia. The blood smear was nearly filled with irregular/convoluted and cleaved nuclear blasts with fine chromatin. The patient received imatinib with induction chemotherapy. After two months, the patient achieved complete remission with undetectable Minimal/Measurable Residual Disease (MRD). By detailing the patient's characteristics and the required tests, the manuscript contributes to a deeper understanding of this complex disease subtype. Furthermore, by examining and comparing the current case with other available cases, the study lays the groundwork for better characterizing the disease and developing more effective therapeutic strategies. 1 6 2024/05/1 1403/2/12 2024/06/22 1403/4/2 Setare Kheyrandish Setare Kheyrandish Student Research Committee, Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 7masterstar@gmail.com Shiva Shadani Shiva Shadani Clinical Research Development Center of Aliasghar Hospital, Iran University of Medical Sciences, Tehran, Iran. shiva_shadani@yahoo.com Aziz Eghbali Aziz Eghbali Clinical Research Development Center of Aliasghar Hospital, Iran University of Medical Sciences, Tehran, Iran. aziz_eghbali@yahoo.com Behzad Poopak Behzad Poopak Department Of Medical Laboratory Sciences, Faculty of Paramedical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. bpoopak@gmail.com Davood Bashash Davood Bashash Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. david_5980@yahoo.com P-190 BCR-ABL Philadelphia CD4+/CD8+ double-positive T-ALL Malignancy Liu-Dumlao, T., et al., Philadelphia-positive acute lymphoblastic leukemia: current treatment options. Curr Oncol Rep, 2012. 14(5): p. 387-94.##Barnes, D.J. and J.V. Melo, Cytogenetic and molecular genetic aspects of chronic myeloid leukaemia. Acta haematologica, 2002. 108(4): p. 180-202.##Sampaio, M.M., et al., Chronic myeloid leukemia-from the Philadelphia chromosome to specific target drugs: A literature review. World journal of clinical oncology, 2021. 12(2):p. 69.##Azad, N.A., et al., Prognostic implication of BCR-ABL fusion transcript variants in chronic myeloid leukemia (CML) treated with imatinib. a first of its kind study on CML patients of kashmir. Asian Pacific journal of cancer prevention: APJCP, 2018. 19(6): p. 1479.##Hazlehurst, L.A., et al., Signaling networks associated with BCR-ABL-dependent transformation. Cancer control : journal of the Moffitt Cancer Center, 2009. 16 2: p. 100- 7.##Iqbal, Z., A comprehensive analysis of breakpoint cluster region-abelson fusion oncogene splice variants in chronic myeloid leukemia and their correlation with disease biology. Indian J Hum Genet, 2014. 20(1): p. 64-8.##Romero-Morelos, P., et al., Frequencies of BCR::ABL1 Transcripts in Patients with Chronic Myeloid Leukemia: A Meta-Analysis. Genes (Basel), 2024. 15(2).##Raanani, P., et al., Philadelphia-chromosome-positive T-lymphoblastic leukemia: acute leukemia or chronic myelogenous leukemia blastic crisis. Acta Haematol, 2005. 113(3): p. 181-9.##Alshomar, A. and R. El Fakih, Philadelphia Chromosome-Positive T-cell Acute Lymphoblastic Leukemia: A Case Report and Review of the Literature. Hematol Oncol Stem Cell Ther, 2022. 15(1): p. 59-62.##Schrappe, M., et al., Philadelphia chromosome-positive (Ph+) childhood acute lymphoblastic leukemia: good initial steroid response allows early prediction of a favorable treatment outcome. 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Jücker, Activated Src kinases downstream of BCR-ABL and Flt3 induces proteasomal degradation of SHIP1 by phosphorylation of tyrosine 1021. Biochimica Et Biophysica Acta-Molecular Cell Research, 2023. 1870(5).##Adnan-Awad, S., et al., Characterization of p190-Bcr-Abl chronic myeloid leukemia reveals specific signaling pathways and therapeutic targets. Leukemia, 2021. 35(7): p. 1964-1975.##Marks, D.I. and C. Rowntree, Management of adults with T-cell lymphoblastic leukemia.Blood, 2017. 129(9): p. 1134-1142.##Lee, S.G., et al., Therapy-related acute lymphoblastic leukemia with t(9;22)(q34;q11.2):a case study and review of the literature. Cancer Genet Cytogenet, 2009. 191(1): p. 51-4.##Dong, Q., et al., Philadelphia chromosome-positive T-cell acute lymphoblastic leukemia: a case report. 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Categorized Serum miRNAs as Potential Biomarkers for Predicting the Progression and Prognosis of Colorectal Cancer 2 2 Background: Colorectal cancer (CRC), a common and aggressive gastrointestinal cancer, presents significant challenges in diagnosis and prognosis prediction despite available detection and treatment options. Many studies emphasized the crucial link between abnormal microRNA regulation and their potential role in cancer development and progression. These miRNAs are recognized as important non-invasive biomarkers for prognosis and overall survival prediction in various cancers, including CRC. Materials and Methods: In this study, we compared the expression patterns of eight miRNAs in the serum of 36 CRC patients with those of 37 healthy controls. The matching criteria included clinicodemographic factors and CRC susceptibility, and the analysis was performed using quantitative real-time PCR (qRT-PCR). Results: The serum miRNA levels of these eight miRNAs (miR-19a, miR-92a, miR-103, miR-106a, miR-107a, miR-150, miR-221, and miR-720) in the study groups are significantly higher compared to the control group. This analysis revealed eight specific miRNAs with varying expression levels in CRC patients.  Furthermore, bioinformatic analysis using data collection and analytical tools has shown that these miRNAs may be associated with important aspects of colorectal cancer development and progression through the PI3K/AKT/PTEN, WNT/CATENIN, and EMT signaling pathways.Conclusion: Our analysis has identified a group of 8 overexpressed miRNAs (miR-19a, miR-92a, miR-103, miR-106a, miR-107a, miR-150, miR-221, and miR-720.) in serum samples of CRC patients. : Although further validation in larger and more diverse groups is necessary,  these findings support a potential mechanism of action for these miRNAs in CRC and their association with essential signaling pathways, including PI3K/AKT/PTEN, WNT/CATENIN, and EMT. 7 14 2024/05/12024/05/11 1403/2/22 2024/06/222024/06/15 1403/3/26 Meral Merve Oğuz Meral Merve Oğuz Department of Internal Medicine, Pamukkale University, Denizli, Turkey/ The Affiliated Hospital of Pamukkale University. monica.khademi@yahoo.com Ehteram Khademi Siahestalkhi Ehteram Khademi Siahestalkhi Department of Medical Genetics, Faculty of Medicine, Pamukkale University, Denizli, Turkey. e.khademi18@gmail.com Arzu Yaren Arzu Yaren Department of Internal Medicine, Pamukkale University, Denizli, Turkey/ The Affiliated Hospital of Pamukkale University. ayaren@pau.tr Aydin Demiray Aydin Demiray Department of Medical Genetics, Faculty of Medicine, Pamukkale University, Denizli, Turkey. ademiray@pau.edu.tr Atike Gökçen Demiray Atike Gökçen Demiray Department of Internal Medicine, Pamukkale University, Denizli, Turkey/ The Affiliated Hospital of Pamukkale University. agakaslan@pau.edu.tr Colorectal cancer (CRC) microRNAs (miRNAs) Biomarkers Prognosis PI3K/AKT/PTEN WNT/CATENIN EMT Hoseini SH, Enayati P, Nazari M, Babakhanzadeh E, Rastgoo M, Sohrabi NB. Biomarker Profile of Colorectal Cancer: Current Findings and Future Perspective. J Gastrointest Cancer. 2024 Jan 2;##Keum N, Giovannucci E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol. 2019 Dec;16(12):713-32.##Zlobec I, Lugli A. Prognostic and predictive factors in colorectal cancer. Postgrad Med J. 2008 Aug;84(994):403-11.##Schreuders EH, Ruco A, Rabeneck L, Schoen RE, Sung JJ, Young GP, et al. Colorectal cancer screening: a global overview of existing programs. Gut. 2015 Oct;64(10):1637-49.##Allison JE, Tekawa IS, Ransom LJ, Adrain AL. A comparison of fecal occult blood tests for colorectal-cancer screening. N Engl J Med. 1996;334(3):155-9.##Koh JL, Yan TD, Glenn D, Morris DL. Evaluation of preoperative computed tomography in estimating peritoneal cancer index in colorectal peritoneal carcinomatosis. Ann Surg Oncol. 2009 Feb;16(2):327-33.##Motalleb G, Sancholi S, Yegane Moghadam A, Talaee R. P53 gene expression evaluation in patients with esophageal cancer using reverse transcriptase real-time polymerase chain reaction. Pajoohandeh J [Internet]. 2015 Aug 10 [cited 2024 Jun 4];20(3):154-62. Available from: http://pajoohande.sbmu.ac.ir/article-1-2023-en.html##Stein, L. C D. Reactome: a database of reactions, pathways and biological processes. Nucleic Acids Research, [Internet]. 2010. Available from: https://reactome.org/##KEGG: Kyoto Encyclopedia of genes and genomes - PubMed [Internet]. [cited 2024 May 30]. Available from: https://pubmed.ncbi.nlm.nih.gov/10592173/##miRBase [Internet]. [cited 2024 May 30]. Available from: https://www.mirbase.org/##miRTarBase: the experimentally validated microRNA-target interactions database [Internet]. [cited 2024 May 30]. Available from: https://mirtarbase.cuhk.edu.cn/~miRTarBase/miRTarBase_2022/php/index.php##TargetScanHuman 8.0 [Internet]. [cited 2024 May 30]. Available from: https://www.targetscan.org/vert_80/##Enrichr [Internet]. [cited 2024 May 30]. Available from: https://maayanlab.cloud/Enrichr/##DAVID Functional Annotation Bioinformatics Microarray Analysis [Internet]. [cited 2024 May 30]. Available from: https://david.ncifcrf.gov/##Sherman BT, Hao M, Qiu J, Jiao X, Baseler MW, Lane HC, et al. DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res. 2022 Jul 5;50(W1): W216-21.##Cytoscape: An Open Source Platform for Complex Network Analysis and Visualization [Internet]. [cited 2024 May 30]. Available from: https://cytoscape.org/##Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res [Internet]. 2019 Jan 8 [cited 2024 May 30];47(D1):D607-13. Available from:##Zhang GJ, Li LF, Yang GD, Xia SS, Wang R, Leng ZW, et al. MiR-92a promotes stem cell-like properties by activating Wnt/β-catenin signaling in colorectal cancer. Oncotarget. 2017 Nov 24;8(60):101760-70.##Liu Y, Liu R, Yang F, Cheng R, Chen X, Cui S, et al. miR-19a promotes colorectal cancer proliferation and migration by targeting TIA1. Mol Cancer. 2017 Mar 4;16(1):53.##Dou L, Meng X, Sui X, Wang S, Shen T, Huang X, et al. MiR-19a regulates PTEN expression to mediate glycogen synthesis in hepatocytes. Sci Rep. 2015;5:11602.##Colakoglu T, Yildirim S, Kayaselcuk F, Nursal TZ, Ezer A, Noyan T, et al. Clinicopathological significance of PTEN loss and the phosphoinositide 3-kinase/Akt pathway in sporadic colorectal neoplasms: is PTEN loss predictor of local recurrence? Am J Surg. 2008 Jun;195(6):719-25.##Peng Y, Huang D, Qing X, Tang L, Shao Z. Investigation of MiR-92a as a Prognostic Indicator in Cancer Patients: a Meta-Analysis. J Cancer. 2019;10(18):4430-41.##Zheng YB, Xiao K, Xiao GC, Tong SL, Ding Y, Wang QS, et al. MicroRNA-103 promotes tumor growth and metastasis in colorectal cancer by directly targeting LATS2. Oncol Lett. 2016 Sep;12(3):2194-200.##Geng L, Sun B, Gao B, Wang Z, Quan C, Wei F, et al. MicroRNA-103 promotes colorectal cancer by targeting tumor suppressors DICER and PTEN. Int J Mol Sci. 2014 May 13;15(5):8458-72.##Nonaka R, Miyake Y, Hata T, Kagawa Y, Kato T, Osawa H, et al. Circulating miR-103 and miR-720 as novel serum biomarkers for patients with colorectal cancer. Int J Oncol. 2015 Sep;47(3):1097-102.##Liu J, Ke F, Chen T, Zhou Q, Weng L, Tan J, et al. MicroRNAs that regulate PTEN as potential biomarkers in colorectal cancer: a systematic review. J Cancer Res Clin Oncol. 2020;146(4):809-20.##Hao H, Xia G, Wang C, Zhong F, Liu L, Zhang D. miR-106a suppresses tumor cell death in colorectal cancer through targeting ATG7. Med Mol Morphol. 2017;50(2):76-85.##Yu FB, Sheng J, Yu JM, Liu JH, Qin XX, Mou B. MiR-19a-3p regulates the Forkhead box F2-mediated Wnt/β-catenin signaling pathway and affects the biological functions of colorectal cancer cells. World J Gastroenterol. 2020 Feb 14;26(6):627-44.##Chen HY, Lin YM, Chung HC, Lang YD, Lin CJ, Huang J, et al. miR-103/107 Promote Metastasis of Colorectal Cancer by Targeting the Metastasis Suppressors DAPK and KLF4. Cancer Res. 2012;72(14):3631-41.##Chen HY, Lang YD, Lin HN, Liu YR, Liao CC, Nana AW, et al. miR-103/107 prolong Wnt/β-catenin signaling and colorectal cancer stemness by targeting Axin2. Sci Rep. 2019 Jul 4;9(1):9687.##Guo YH, Wang LQ, Li B, Xu H, Yang JH, Zheng LS, et al. The Wnt/β-catenin pathway transactivates microRNA-150 and promotes EMT of colorectal cancer cells by suppressing CREB signaling. Oncotarget. 2016 Jul 5;7(27):42513-26.##Zhao F, Yang Z, Gu X, Feng L, Xu M, Zhang X. miR-92b-3p Regulates Cell Cycle and Apoptosis by Targeting CDKN1C, Thereby Affecting the Sensitivity of Colorectal Cancer Cells to Chemotherapeutic Drugs. Cancers. 2021;13(13):3323.##Hong Z, Feng Z, Sai Z, Tao S. PER3, a novel target of miR-103, plays a suppressive role in colorectal cancer in vitro. BMB Rep. 2014 Sep;47(9):500-5.##Debnath P, Huirem RS, Dutta P, Palchaudhuri S. Epithelial-mesenchymal transition and its transcription factors. Biosci Rep. 2022 Jan 28;42(1):BSR20211754.##Li C, Du X, Xia S, Chen L. MicroRNA-150 inhibits the proliferation and metastasis potential of colorectal cancer cells by targeting iASPP. Oncol Rep. 2018;##Ameri A, Ahmed HM, Pecho RDC, Arabnozari H, Sarabadani H, Esbati R, et al. Diverse activity of miR-150 in Tumor development: shedding light on the potential mechanisms. Cancer Cell Int. 2023 Nov 3;23(1):261.##Wang X, Kuang Y, Shen X, Zhou H, Chen Y, Han Y, et al. Evaluation of miR-720 prognostic significance in patients with colorectal cancer. Tumor Biol. 2015 Feb 1;36(2):719-27.## ##

Evaluating Adverse Events in COVID-19 Recovered Convalescent Plasma Donors: A Comprehensive Analysis 2 2 Background: The emergence of the COVID-19 pandemic prompted the exploration of convalescent plasma therapy (CPT) as a potential treatment modality. This study provides a comprehensive understanding of adverse events in COVID-19-recovered convalescent plasma (CP) donors for optimizing donor safety and refining donation protocols. The aim is to quantify the type and severity of adverse events associated with CP donation. Materials and Methods: The present one-year retrospective study was undertaken in the blood center of a tertiary care hospital of Western Uttar Pradesh that was a multicentric site in the ICMR Placid trial and a dedicated COVID hospital during the first and second wave in India. Data was analyzed from donor adverse events (DARs) captured during the study period and evaluated for different parameters namely age, gender, body weight, donor status (first-time donor or previous donor), body mass index, blood volume processed, plasma volume collected and lag time between negative RT-PCR report and plasmapheresis. To determine the significance of variations in rates of DARs, Chi-square test was performed (p-value <0.05 considered significant). Results: A total of 769 donations were performed in the study duration. The maximum donors were between the age group of 26-33 years with 301 donations were from this age group.  Out of 769 donations, 648 donors (84.3%) showed no DARs, while 121 donors (15.7%) experienced adverse reactions. Conclusion: Our findings provide essential insights into donor safety, hoping to support and plan future pandemic response strategies against novel infectious diseases. 15 23 2024/05/12024/05/112024/03/9 1402/12/19 2024/06/222024/06/152024/06/13 1403/3/24 Shalini Bahadur Shalini Bahadur Department of Pathology, Government Institute of Medical Sciences, Greater Noida Shalini.bahadur2008@rediffmail.com Bhumika Gupta Bhumika Gupta Department of Pathology, Government Institute of Medical Sciences, Greater Noida drshalinishukla.8@gmail.com Shalini Shukla Shalini Shukla Department of Pathology, Government Institute of Medical Sciences, Greater Noida Shivani.kalhan69@gmail.com Paridhi - Paridhi - Department of Pathology, Government Institute of Medical Sciences, Greater Noida paridhi.dr@gmail.com Shivani Kalhan Shivani Kalhan Department of Pathology, Government Institute of Medical Sciences, Greater Noida drbhumigupta@gmail.com Madhuvan Gupta Madhuvan Gupta Department of Pathology, Government Institute of Medical Sciences, Greater Noida drmadhuvangupta@gmail.com Plasmapheresis Novel infections Donor safety Adverse reactions. Filip R, GheorghitaPuscaselu R, Anchidin-Norocel L, Dimian M, Savage WK. Global Challenges to Public Health Care Systems during the COVID-19 Pandemic: A Review of Pandemic Measures and Problems. J Pers Med. 2022 Aug 7;12(8):1295. doi: 10.3390/jpm12081295. PMID: 36013244; PMCID: PMC9409667.##Peng HT, Rhind SG, Beckett A. Convalescent Plasma for the Prevention and Treatment of COVID-19: A Systematic Review and Quantitative Analysis. JMIR Public Health Surveill. 2021 Apr 7;7(4):e25500. doi: 10.2196/25500. Erratum in: JMIR Public Health Surveill. 2021 Jun 30;7(6):e31554. PMID: 33825689; PMCID: PMC8245055.##Abolghasemi H, Eshghi P, Cheraghali AM, ImaniFooladi AA, BoloukiMoghaddam F, Imanizadeh S, MoeiniMaleki M, Ranjkesh M, Rezapour M, Bahramifar A, Einollahi B, Hosseini MJ, Jafari NJ, Nikpouraghdam M, Sadri N, Tazik M, Sali S, Okati S, Askari E, Tabarsi P, Aslani J, Sharifipour E, Jarahzadeh MH, Khodakarim N, Salesi M, Jafari R, Shahverdi S. Clinical efficacy of convalescent plasma for treatment of COVID-19 infections: Results of a multicenter clinical study. TransfusApher Sci. 2020 Oct;59(5):102875. doi: 10.1016/j.transci.2020.102875. Epub 2020 Jul 15. PMID: 32694043; PMCID: PMC7362821.##Piyush R, Rajarshi K, Khan R, Ray S. Convalescent plasma therapy: a promising coronavirus disease 2019 treatment strategy. Open Biol. 2020 Sep;10(9):200174. doi: 10.1098/rsob.200174. Epub 2020 Sep 9. PMID: 32898468; PMCID: PMC7536086.##Casadevall A, Pirofski LA. The convalescent sera option for containing COVID-19. J Clin Invest. 2020 Apr 1;130(4):1545-1548. doi: 10.1172/JCI138003. PMID: 32167489; PMCID: PMC7108922.##Al-Riyami AZ, Schäfer R, van den Berg K, Bloch EM, Estcourt LJ, Goel R, Hindawi S, Josephson CD, Land K, McQuilten ZK, Spitalnik SL, Wood EM, Devine DV, So-Osman C. Clinical use of Convalescent Plasma in the COVID-19 pandemic: a transfusion-focussed gap analysis with recommendations for future research priorities. Vox Sang. 2021 Jan;116(1):88-98. doi: 10.1111/vox.12973. Epub 2020 Sep 3. PMID: 32542847; PMCID: PMC7891452.##Crocco I, Franchini M, Garozzo G, Gandini AR, Gandini G, Bonomo P, Aprili G. Adverse reactions in blood and apheresis donors: experience from two Italian transfusion centres. Blood Transfus. 2009 Jan;7(1):35-8. doi: 10.2450/2008.0018-08. PMID: 19290078; PMCID: PMC2652234.##Kasprisin DO, Glynn SH, Taylor F, Miller KA. Moderate and severe reactions in blood donors. Transfusion. 1992 Jan;32(1):23-6. doi: 10.1046/j.1537-2995.1992.32192116426.x. PMID: 1731431.##Ogata H, Iinuma N, Nagashima K, Akabane T. Vasovagal reactions in blood donors. Transfusion. 1980 Nov-Dec;20(6):679-83. doi: 10.1046/j.1537-2995.1980.20681057157.x. PMID: 7434451. Ref DRUG CON GEN##Ministry of Health and Family Welfare, Government of India. Drugs and Cosmetics Act 1940 and Rules 1945, Amended. [accessed on October 11, 2023]. Available from: https://cdsco.gov.in/opencms/export/sites/CDSCO_WEB/Pdf-documents/acts_rules/2016DrugsandCosmeticsAct1940Rules1945.pdf##Bisht A, Marwaha N, Kaur R, Gupta D, Chhabra R. Haemovigilance Programme of India: Comparative analysis of transfusion reactions reported over a 5-year period through two reporting formats and key recommendations for blood safety. Asian J Transfus Sci. 2020 Jul-Dec;14(2):103-116. doi: 10.4103/ajts.ajts_192_20. Epub 2020 Dec 19. PMID: 33767535; PMCID: PMC7983136.##Narayan S, Shanmugaranjan S, Griffiths A, Roberts D. Vasovagal reactions reported in COVID-19 convalescent plasma donors-NHSBT experience.Transfusion Medicine ; 31(SUPPL 1):10, 2021.##He R, Lin H, Xie S, Lv Q, Kong Y, Li L, Xu H, Wang J, Li W, Fang P, Wu Y, Liu Z. Donor tolerability of convalescent plasma donation. J ClinApher. 2021 Jun;36(3):429-436. doi: 10.1002/jca.21882. Epub 2021 Feb 15. PMID: 33587767; PMCID: PMC8013347.##Cho, JH, Rajbhandary, S, van Buren, NL, et al. The safety of COVID-19 convalescent plasma donation: A multi-institutional donor hemovigilance study. Transfusion. 2021; 61: 2668-2676.##Crocco A, D'Elia D. Adverse reactions during voluntary donation of blood and/or blood components. A statistical-epidemiological study. Blood Transfus. 2007 Jul;5(3):143-52. doi: 10.2450/2007.0005-07. PMID: 19204767; PMCID: PMC2535889.##Del Fante C, Franchini M, Baldanti F, Percivalle E, Glingani C, Marano G, Mengoli C, Mortellaro C, Viarengo G, Perotti C, Liumbruno GM. A retrospective study assessing the characteristics of COVID-19 convalescent plasma donors and donations. Transfusion. 2021 Mar;61(3):830-838. doi: 10.1111/trf.16208. Epub 2020 Dec 14. PMID: 33231325; PMCID: PMC7753739.##McLeod BC, Price TH, Owen H, Ciavarella D, Sniecinski I, Randels MJ, Smith JW. Frequency of immediate adverse effects associated with apheresis donation. Transfusion. 1998 Oct;38(10):938-43. doi: 10.1046/j.1537-2995.1998.381098440858.x. PMID: 9767744.##Philip J, Sarkar RS, Pathak A. Adverse events associated with apheresis procedures: Incidence and relative frequency. Asian J Transfus Sci. 2013 Jan;7(1):37-41. doi: 10.4103/0973-6247.106730. PMID: 23559763; PMCID: PMC3613659.##Arora D, Garg K, Kaushik A, Sharma R, Rawat DS, Mandal AK. A Retrospective Analysis of Apheresis Donor Deferral and Adverse Reactions at a Tertiary Care Centre in India. J ClinDiagn Res. 2016 Nov;10(11):EC22-EC24. doi: 10.7860/JCDR/2016/20707.8925. Epub 2016 Nov 1. PMID: 28050376; PMCID: PMC5198329.##Khade, A. L., Poflee, S. V, Parate, S. N., Gadhave, S. B., Golhar, V. S., ;Kumbhalkar, D. T. (2022). Single Donor Plasmapheresis for COVID-19: An Experience from a Tertiary Care Hospital Based Blood Centre. National Journal of Laboratory Medicine, 11(4). ##https://doi.org/10.7860/NJLM/2022/55562.2677## ##

High Variability in HLA-DRB1*03, a Predisposing Allele in Acute Lymphoblastic Leukemia 2 2 Acute lymphoblastic leukemia (ALL) remains a significant health concern, particularly in children, with genetic predisposition playing a crucial role in its etiology. Among the predisposing HLA Class II alleles, —DRB1*03 has emerged as a notable candidate associated with increased susceptibility to ALL. This study aims to investigate the extent of variability within the HLA-DRB1 alleles as genetic biomarkers and its implications in ALL pathogenesis. Through methods of polymerase chain reaction—sequence-specific oligonucleotides (PCR-SSO) and sequence-based typing (SBT) analysis, our data revealed HLA-DRB1*16 as another genetic risk and HLA-DRB1*07 and HLA-DRB1*12 alleles as protective alleles in ALL patients. Further sequencing demonstrates a remarkable diversity in the HLA-DRB1*03 allele in ALL patients but none among the HLA-DRB1*16 alleles compared to normal samples. Our findings confirmed the association of HLA-DRB1 alleles with ALL and shed light on SNPs or mutations in the risk alleles. Genetic variability in HLA-DRB1 alleles is a significant factor to consider in improving outcomes in immunotherapy. 24 33 2024/05/12024/05/112024/03/92024/03/29 1403/1/10 2024/06/222024/06/152024/06/132024/05/24 1403/3/4 Norfarazieda Hassan Norfarazieda Hassan UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400 UPM, Selangor, Malaysia fara.hassan@usm.my Siti Zuleha Idris Siti Zuleha Idris Department of Pathology, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia zuleha@moh.gov.my Kian Meng Chang Kian Meng Chang Department of Hematology, Hospital Ampang, Clinical Hematology Laboratory, Jalan Mewah Utara, Pandan Mewah, Ampang, Selangor 68000, Malaysia drchangkm@gmail.com Raudhawati Osman Raudhawati Osman Hematology Unit, Hospital Kuala Lumpur, Jalan Pahang, 50586 Wilayah, Persekutuan Kuala Lumpur, Malaysia raudhaosman@yahoo.com Hishamshah Mohd Ibrahim Hishamshah Mohd Ibrahim Pediatric Department, Hospital Kuala Lumpur, 50586 Wilayah, Persekutuan Kuala Lumpur, Malaysia drhishamshah@moh.gov.my Jasbir Singh Dhaliwal Jasbir Singh Dhaliwal Allergy and Immunology Research Centre, Institute for Medical Research, 50588 Jalan Pahang, Kuala Lumpur jasbir@gmail.com Maha Abdullah Maha Abdullah Department of Pathology, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia maha@upm.edu.my Human leukocyte antigen HLA-DRB1*03 HLA class II Acute lymphoblastic leukemia Pre-B ALL Karp DR, Teletski CL, Scholl P, Geha R, Long EO. 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Optimizing Patient Blood Management in Cardiac Surgery: A Systematic Review 2 2 Background: Heart diseases are typically treated with cardiac surgery, which often requires preoperative, intraoperative, and postoperative blood transfusion. However, blood transfusion is a risk factor for serious complications after cardiac surgery, including death. Patient Blood Management (PBM) programs were developed to mitigate the risks of blood transfusion by reducing its use in cardiac surgery. Objective: This systematic review aims to study the currently published literature on PBM strategies that effectively reduce the rates of preoperative, intraoperative, and postoperative blood transfusion for cardiac surgery. Methodology: This systematic review analyzed preoperative blood management strategies in cardiac surgery, focusing on studies published between 2018 and 2024 designed to reduce blood transfusion rates. The study utilized a modified 2022 protocol for systematic reviews and meta-analysis, grading evidence using a 2008 system, and selected 21 studies for a systematic review. Results: The studies identified 12 PBM strategies, including iron therapy, Aminocaproic acid, Cardiopulmonary by-pass system, cell salvage, Perfusion Blood Collection, gel foam patches, Large-volume acute normovolemic hemodilution, Platelets Transfusion Therapy, Modified Ultrafiltration, TEM-based algorithms, and restrictive management of SVO2, which significantly reduced blood transfusion volumes and rates before, during, and after cardiac surgery. Conclusion: The 12 PBM strategies identified are valuable additions to the current list, but further clinical evaluation is needed to improve their efficacy and safety in cardiac surgery. 34 50 2024/05/12024/05/112024/03/92024/03/292024/04/2 1403/1/14 2024/06/222024/06/152024/06/132024/05/242024/05/24 1403/3/4 Sultan Ghazzay Alotaibi Sultan Ghazzay Alotaibi Cardiac Center, King Fahd Armed Forces Hospital, Ministry of Defense, Jeddah, Saudi Arabia. sultanalotaibi678@outlook.com Muneeb Ammar Alnouri Muneeb Ammar Alnouri Cardiac Center, King Fahd Armed Forces Hospital, Ministry of Defense, Jeddah, Saudi Arabia. muneebalnouri733@outlook.com Rawaa Mahmoud Sulaiman Rawaa Mahmoud Sulaiman Family Medicine Department, Dr. Sulaiman Fakeeh Hospital, Jeddah, Saudi Arabia rawaamsulaiman78@outlook.com Abdulkhalek Abduljaleel Abdulkhalek Abduljaleel King Fahad General Hospital, Jeddah, Saudi Arabia. Abdulkhalek.A.Abduljalee@outlook.com Ahmed Foad Bogari Ahmed Foad Bogari King Fahad General Hospital, Jeddah, Saudi Arabia. Ahemd.Bogari7@outlook.com Hani Nabeel Mufti Hani Nabeel Mufti King Faisal Cardiac Center, King Abdul-Aziz Medical City, Ministry of National Guard Health Affairs, Jeddah, Saudi Arabia Mufti@outlook.com Blood transfusion Cardiac surgery Patient blood management Systematic review Bleeding disorder. Senst B, Kumar A, Diaz RR. Cardiac surgery. StatPearls [Internet]: StatPearls Publishing; 2022.##Barker CM, Goel K. Transcatheter Tricuspid Interventions: Past, Present, and Future. Methodist DeBakey Cardiovascular Journal. 2023;19(3):57.##Yasuda N, Goto K, Kuribayashi Y, Ohchi Y, Kitano T. Incidence, outcome, and risk factors of cardiovascular surgery-associated disseminated intravascular coagulation: a single-center retrospective study. Journal of Clinical Medicine. 2022;11(13):3633.##Woldendorp K, Manuel L, Srivastava A, Doane M, Bassin L, Marshman D. Perioperative transfusion and long-term mortality after cardiac surgery: a meta-analysis. General Thoracic and Cardiovascular Surgery. 2023;71(6):323-30.##Hinton JV, Xing Z, Fletcher CM, Perry LA, Karamesinis A, Shi J, et al. Cryoprecipitate transfusion after cardiac surgery. Heart, Lung and Circulation. 2023;32(3):414-23.##Maisat W, Yuki K. Narrative Review of Systemic Inflammatory Response Mechanisms in Cardiac Surgery and Immunomodulatory Role of Anesthetic Agents. Annals of Cardiac Anaesthesia. 2023;26(2):133.##Sugisman SB, Agustian R, Putra PLP, Simorangkir BP. TOPICAL APPLICATION EFFECT OF TRANEXAMIC ACID IN POSTOPERATIVE BLEEDING AND BLOOD PRODUCTS TRANSFUSION AFTER CARDIAC SURGERY. 2022.##Yousuf MS, Samad K, Ahmed SS, Siddiqui KM, Ullah H, Yousuf MS. Cardiac Surgery and Blood-Saving Techniques: An Update. Cureus. 2022;14(1).##Ștefan M, Tomescu D, Predoi C, Goicea R, Perescu M, Popescu M, et al. Less (Transfusion) Is More-Enhancing Recovery through Implementation of Patient Blood Management in Cardiac Surgery. A Retrospective, Single-Centre Study of 1174 Patients. Journal of Cardiovascular Development and Disease. 2023;10(7):266.##Breel JS, Wensing AG, Eberl S, Preckel B, Schober P, Müller MC, et al. Patients with infective endocarditis undergoing cardiac surgery have distinct ROTEM profiles and more bleeding complications compared to patients without infective endocarditis. Plos one. 2023;18(4):e0284329.##Chegini A, Jamalian A, Abolhassani MR, Alavi AB. A review of issues and challenges of implementation of patient blood management. Asian Journal of Transfusion Science. 2023.##Shou BL, Aravind P, Ong CS, Alejo D, Canner JK, Etchill EW, et al. Early reexploration for bleeding is associated with improved outcome in cardiac surgery. The Annals of Thoracic Surgery. 2023;115(1):232-9.##Yang K, Huang H, Dai R, Zhang J, Wei X, Gao F, et al. Modified cardiopulmonary bypass with low priming volume for blood conservation in cardiac valve replacement surgery. Journal of Cardiothoracic Surgery. 2023;18(1):1-11.##Ali SME, Hafeez MH, Nisar O, Fatima S, Ghous H, Rehman M. Role of preoperative erythropoietin in the optimization of preoperative anemia among surgical patients-A systematic review and meta-analysis. Hematology, Transfusion and Cell Therapy. 2022;44:76-84.##Cain MT, Joyce DL, Szabo A, Wu R, Kohmoto T, Joyce LD, et al. Reduced Morbidity and Mortality Associated With Minimally Invasive Single-vessel Coronary Artery Bypass Compared With Conventional Sternotomy. Annals of Surgery. 2023;277(5):e1176-e83.##Elkhouly M, Fouad A. The Role of Absorbable Gelatin Sponge (Gel Foam) in Control of Sternal Bleeding during Cardiac Surgery. The Egyptian Journal of Hospital Medicine. 2023;90(1):335-42.##Hasan O, Tung RC, Freeman H, Taylor W, Helmer SD, Reyes J, et al. Thromboelastography after cardiopulmonary bypass: does it save blood products? Kansas Journal of Medicine. 2022;15:27.##Hinton JV, Fletcher CM, Perry LA, Greifer N, Hinton JN, Williams-Spence J, et al. Platelet versus fresh frozen plasma transfusion for coagulopathy in cardiac surgery patients. Plos one. 2024;19(1):e0296726.##Kelava M, Mehta A, Sale S, Gillinov M, Johnston D, Thuita L, et al. Effectiveness and Safety of E-aminocaproic Acid in Overall and Less-Invasive Cardiac Surgeries. Journal of Cardiothoracic and Vascular Anesthesia. 2022;36(10):3780-90.##Kloeser R, Buser A, Bolliger D. Treatment strategies in anemic patients before cardiac surgery. Journal of Cardiothoracic and Vascular Anesthesia. 2023;37(2):266-75.##Ledergerber K, Hollinger A, Zimmermann S, Todorov A, Trutmann M, Gallachi L, et al. Impact of Additional Administration of von Willebrand Factor Concentrates to Thrombocyte Transfusion in Perioperative Bleeding in Cardiac Surgery. Transfusion Medicine and Hemotherapy. 2024;51(1):22.##Liu H-M, Tang X-s, Yu H, Yu H. The efficacy of intravenous iron for treatment of anemia before cardiac surgery: An updated systematic review and meta-analysis with trial sequential analysis. Journal of Cardiothoracic Surgery. 2023;18(1):16.##Matzek LJ, LeMahieu AM, Madde NR, Johanns DP, Karon B, Kor DJ, et al. A contemporary analysis of phlebotomy and iatrogenic anemia development throughout hospitalization in critically ill adults. Anesthesia & Analgesia. 2022;135(3):501-10.##Ming Y, Zhang F, Yao Y, Cheng Z, Yu L, Sun D, et al. Large volume acute normovolemic hemodilution in patients undergoing cardiac surgery with intermediate-high risk of transfusion: A randomized controlled trial. Journal of Clinical Anesthesia. 2023;87:111082.##Naguib AN, Carrillo SA, Corridore M, Bigelow AM, Walczak A, Tram NK, et al. A ROTEM-guided algorithm aimed to reduce blood product utilization during neonatal and infant cardiac surgery. The Journal of ExtraCorporeal Technology. 2023;55(2):60-9.##Navaratnam M, Mendoza JM, Zhang S, Boothroyd D, Maeda K, Kamra K, et al. Activated 4-factor prothrombin complex concentrate as a hemostatic adjunct for neonatal cardiac surgery: a propensity score-matched cohort study. Anesthesia & Analgesia. 2023;136(3):473-82.##Amanvermez Senarslan D, Yildirim F, Kurdal AT, Damar A, Ozturk T, Tetik O. Efficacy and cost-effectiveness of cell saver usage in the repair of thoracic aortic aneurysms and dissections. Perfusion. 2022;37(7):722-8.##Shi J, Zhou C, Pan W, Sun H, Liu S, Feng W, et al. Effect of high-vs low-dose tranexamic acid infusion on need for red blood cell transfusion and adverse events in patients undergoing cardiac surgery: the OPTIMAL randomized clinical trial. Jama. 2022;328(4):336-47.##Smith MM, Schroeder DR, Nelson JA, Mauermann WJ, Welsby IJ, Pochettino A, et al. Prothrombin Complex Concentrate vs Plasma for Post-Cardiopulmonary Bypass Coagulopathy and Bleeding: A Randomized Clinical Trial. JAMA surgery. 2022;157(9):757-64.##Sutherland L, Houchin A, Wang T, Wang S, Moitra V, Sharma A, et al. Impact of early, low-dose factor VIIa on subsequent transfusions and length of stay in cardiac surgery. Journal of Cardiothoracic and Vascular Anesthesia. 2022;36(1):147-54.##Zeroual N, Blin C, Saour M, David H, Aouinti S, Picot M-C, et al. Restrictive transfusion strategy after cardiac surgery: role of central venous oxygen saturation trigger: a randomized controlled trial. Anesthesiology. 2021;134(3):370-80.##Zhou Y, Yang C, Jin Z, Zhang B. Intraoperative use of cell saver devices decreases the rate of hyperlactatemia in patients undergoing cardiac surgery. Heliyon. 2023;9(5).##Gunaydin S, Robertson C, Budak AB, Gourlay T. Comparative evaluation of blood salvage techniques in patients undergoing cardiac surgery with cardiopulmonary bypass. 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Evaluation of the Home Safety and Child-friendly Environment for Children with Bleeding Tendency Disorders 2 2 Background: This study aims to assess the safety level of the different home parts for children with a bleeding tendency disorder (especially hemophilia) and identify the elements that affect this safety. Materials and methods: We conducted a cross-sectional study on the children referred to the Mofid Children’s Hospital from the beginning of 2018 to the end of 2020. Information was gathered via a checklist. Inclusion criteria were children between 1 to 5 years old with bleeding tendencies, and exclusion criteria were the presence of other disorders. The safety was measured in five areas at home: 1- physical conditions 2- kitchen 3- bathroom 4- toys 5- first aid equipment and essential phone numbers. Results: Forty-one children participated in this study which 31 (75.61 %) were boys. Eleven (28.95 %) children experienced zero accidents at home and eight (21.05 %) children experienced more than three accidents at home. The Mean and 95% confidence interval scores were 7.97 (7.37-8.57) for the physical condition section, 8.22 (7.73-8.70) for the kitchen section, 8.15 (7.66-8.65) for the bathroom section, 7.93 (7.15-8.71) for the toys section, and 7.30 (6.60-8.01) for the first aid equipment and essential phone numbers section. The physical condition safety score was significantly higher in families whose fathers had a college education than in fathers with secondary and diploma education (P-value = 0.024). The kitchen section safety score was significantly higher in families where the father has a freelance job than the employee or worker (P-value = 0.040). Conclusion: The mother’s age, father’s educational level, and father’s job are the factors that affect the level of safety significantly. Providing toys that are age-appropriate and safe (without separable parts or holes) could be an important point for parents with children with bleeding disorders. 51 59 2024/05/12024/05/112024/03/92024/03/292024/04/22024/03/1 1402/12/11 2024/06/222024/06/152024/06/132024/05/242024/05/242024/04/19 1403/1/31 Fereshteh Karbasian Fereshteh Karbasian Department of pediatric gastroenterology and hepatology, Iran University of Medical Sciences, Tehran, Iran. karbasian.md@gmail.com Maral Nikfarjam Maral Nikfarjam Department of Pediatric, Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Nikfarjammaral8@gmail.com Kiarash Noorizadeh Kiarash Noorizadeh Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran kiarash.noorizadeh@yahoo.com Ali Abbasi-Kashkooli Ali Abbasi-Kashkooli Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran ali.ab.kash.1999@gmail.com Peyman Eshghi Peyman Eshghi Pediatric Congenital Hematologic Disorders, Research Institute for Children Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran peshghi63@gmail.com Hamid Reihani Hamid Reihani Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran hmid.reihani@gmail.com Bleeding tendency disorders Hemophilia Home safety Living condition Blood Coagulation Disorders. Blanchette VS, Sparling C, Turner C. Inherited bleeding disorders. Bailliere's clinical haematology. 1991;4(2):291-332.##Mannucci PM, Tuddenham EG. The hemophilias--from royal genes to gene therapy. The New England journal of medicine. 2001;344(23):1773-9.##Hedner U, Ginsburg D, Lusher JM, High KA. Congenital Hemorrhagic Disorders: New Insights into the Pathophysiology and Treatment of Hemophilia. Hematology American Society of Hematology Education Program. 2000:241-65.##Iorio A, Stonebraker JS, Chambost H, Makris M, Coffin D, Herr C, et al. Establishing the Prevalence and Prevalence at Birth of Hemophilia in Males: A Meta-analytic Approach Using National Registries. Annals of internal medicine. 2019;171(8):540-6.##Phillips MD, Santhouse A. von Willebrand Disease: Recent Advances in Pathophysiology and Treatment. The American Journal of the Medical Sciences. 1998;316(2):77-86.##https://doi.org/10.1016/S0002-9629(15)40382-9##Sadler JE, Budde U, Eikenboom JC, Favaloro EJ, Hill FG, Holmberg L, et al. Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor. 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Family Dynamics of the Stay-at-Home Father and Working Mother Relationship. Am J Mens Health. 2015;9(5):410-20.##Mohammadinia L, Khorasani-Zavareh D, Gharibzadeh S, Roshanferk P, Malekafzali H. Social Determinants of Health and Home Safety for Under-five Children in a Neighbor's Tehran, Iran. Int J Prev Med. 2018;9:109.##Munford LA, Fichera E, Sutton M. Is owning your home good for your health? Evidence from exogenous variations in subsidies in England. Econ Hum Biol. 2020;39:100903.## ##

Type 2N von Willebrand Disease: Overcoming Diagnostic Challenges for Accurate Diagnosis 2 2 Von Willebrand Factor (vWF) defects can cause von Willebrand Disease (vWD), which is known to be the most prevalent inherited bleeding disorder worldwide. According to the latest classifications, vWD is categorized into three main types. Types 1 and 3 are quantitative defects, while type 2 vWD is caused by qualitative abnormalities in vWF. Furthermore, ISTH classifies type 2 vWD is into four subtypes known as 2A, 2B, 2N, and 2M. Type 2N vWD is an uncommon type of vWD that is inherited in an autosomal recessive pattern. In this type, the binding capacity of vWF to Factor VIII (FVIII) is reduced, resulting in FVIII's shortened half-life in the patient's plasma. Due to the pathophysiology of Type 2N vWD, affected individuals exhibit signs and symptoms similar to those with mild to moderate hemophilia A. These symptoms include mucocutaneous bleeding or bleeding following trauma or surgery. Furthermore, the primary laboratory findings of affected individuals are comparable to those of hemophilia A patients, with Factor VIII levels ranging from 1 to 40 U/dL. It is crucial to differentiate these disorders for optimal treatment and accurate genetic counseling. Physicians may use a combination of clinical assessment, family history, bleeding scores, and laboratory tests to differentiate between the two disorders. Further genetic testing may be necessary to confirm the diagnosis and assess the risk of inheritance. This review outlines methods for diagnosing type 2N vWD and distinguishing it from hemophilia A, based on published papers and current guidelines. 60 69 2024/05/12024/05/112024/03/92024/03/292024/04/22024/03/12023/03/20 1401/12/29 2024/06/222024/06/152024/06/132024/05/242024/05/242024/04/192024/04/19 1403/1/31 Behnam Azari Behnam Azari Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine behnam140@gmail.com Minoo Ahmadinejad Minoo Ahmadinejad Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine minooam@gmail.com von Willebrand Factor von Willebrand Disease Hemophilia A. VON WILLEBRAND, F., Hereditar pseudo-hemophili. Finska Lakaresallskapets Handlinger, 1926. 68: p. 87-112.##James, P.D., et al., ASH ISTH NHF WFH 2021 guidelines on the diagnosis of von Willebrand disease. Blood advances, 2021. 5(1): p. 280-300.##Seidizadeh, O., F. Peyvandi, and P.M. Mannucci, Von Willebrand disease type 2N: an update. Journal of Thrombosis and Haemostasis, 2021. 19(4): p. 909-916.##Federici, A.B., Clinical and laboratory diagnosis of VWD. Hematology 2014, the American Society of Hematology Education Program Book, 2014. 2014(1): p. 524-530.##Ng, C., D.G. Motto, and J. Di Paola, Diagnostic approach to von Willebrand disease. Blood, The Journal of the American Society of Hematology, 2015. 125(13): p. 2029-2037.##SADLER, J.E., et al., Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor. Journal of Thrombosis and Haemostasis, 2006. 4(10): p. 2103-2114.##Lillicrap, D., Translational medicine advances in von Willebrand disease. Journal of Thrombosis and Haemostasis, 2013. 11: p. 75-83.##Mazurier, C., et al., Type 2N von Willebrand disease: clinical manifestations, pathophysiology, laboratory diagnosis and molecular biology. Best Practice & Research Clinical Haematology, 2001. 14(2): p. 337-347.##Mazurier, C., et al., Evidence for a von Willebrand factor defect in factor VIII binding in three members of a family previously misdiagnosed mild haemophilia A and haemophilia A carriers: consequences for therapy and genetic counselling. British journal of haematology, 1990. 76(3): p. 372-379.##Zadeh, O.S., et al., Are Iranian patients with von Willebrand disease type 2N properly differentiated from hemophilia A and do they receive appropriate treatment? Blood Coagulation & Fibrinolysis, 2020. 31(6): p. 382-386.##Mazurier, C., et al., A new von Willebrand factor (vWF) defect in a patient with factor VIII (FVIII) deficiency but with normal levels and multimeric patterns of both plasma and platelet vWF. Characterization of abnormal vWF/FVIII interaction. 1990.##Nishino, M., et al., New variant of von Willebrand disease with defective binding to factor VIII. 1989.##Lenting, P.J., O.D. Christophe, and C.V. Denis, von Willebrand factor biosynthesis, secretion, and clearance: connecting the far ends. Blood, The Journal of the American Society of Hematology, 2015. 125(13): p. 2019-2028.##McPherson, R.A. and M.R. Pincus, Henry's clinical diagnosis and management by laboratory methods E-book. 2021: Elsevier Health Sciences.##Springer, T.A., von Willebrand factor, Jedi knight of the bloodstream. Blood, The Journal of the American Society of Hematology, 2014. 124(9): p. 1412-1425.##Sadler, J., von Willebrand factor assembly and secretion. Journal of Thrombosis and Haemostasis, 2009. 7: p. 24-27.##Drakeford, C., et al., von Willebrand factor links primary hemostasis to innate immunity. Nature Communications, 2022. 13(1): p. 6320.##Terraube, V., J. O'donnell, and P. Jenkins, Factor VIII and von Willebrand factor interaction: biological, clinical and therapeutic importance. Haemophilia, 2010. 16(1): p. 3-13.##Mazurier, C., et al., Biological effect of desmopressin in eight patients with type 2N ('Normandy') von Willebrand disease. British journal of haematology, 1994. 88(4): p. 849-854.##Tuddenham, E., et al., Response to infusions of polyelectrolyte fractionated human factor VIII concentrate in human haemophilia A and von Willebrand's disease. British journal of haematology, 1982. 52(2): p. 259-267.##Gensana, M., et al., Influence of von Willebrand factor on the reactivity of human factor VIII inhibitors with factor VIII. Haemophilia, 2001. 7(4): p. 369-374.##https://doi.org/10.1111/j.1365-2516.2001.00526.x##Gringeri, A., et al., Immune tolerance induction with a high purity von Willebrand factor/VIII complex concentrate in haemophilia A patients with inhibitors at high risk of a poor response. Haemophilia, 2007. 13(4): p. 373-379.##Peyvandi, F., I. Garagiola, and L. Baronciani, Role of von Willebrand factor in the haemostasis. Blood Transfusion, 2011. 9(Suppl 2): p. s3.##Chiu, P.-L., et al., Mapping the interaction between factor VIII and von Willebrand factor by electron microscopy and mass spectrometry. Blood, The Journal of the American Society of Hematology, 2015. 126(8): p. 935-938.##Wise, R.J., et al., The role of von Willebrand factor multimers and propeptide cleavage in binding and stabilization of factor VIII. Journal of Biological Chemistry, 1991. 266(32): p. 21948-21955.##Zhou, Y.-F., et al., Sequence and structure relationships within von Willebrand factor. Blood, The Journal of the American Society of Hematology, 2012. 120(2): p. 449-458.##Shiltagh, N., et al., Solution structure of the major factor VIII binding region on von Willebrand factor. Blood, The Journal of the American Society of Hematology, 2014. 123(26): p. 4143-4151.##Hampshire, D.J. and A.C. Goodeve. The international society on thrombosis and haematosis von Willebrand disease database: an update. in Seminars in thrombosis and hemostasis. 2011. © Thieme Medical Publishers.##Roberts, J.C. and V.H. Flood, Laboratory diagnosis of von Willebrand disease. Int J Lab Hematol, 2015. 37 Suppl 1(Suppl 1): p. 11-7.##Agne, J., et al., VWD type 2N (Normandy) in two sisters. Haemophilia, 2015. 21(3): p. e223-e225.##van Meegeren, M., et al., Clinical phenotype in genetically confirmed von Willebrand disease type 2N patients reflects a haemophilia A phenotype. Haemophilia, 2015. 21(5): p. e375-e383.##Tagliaferri, A., et al., The natural history of mild haemophilia: a 30‐year single centre experience. Haemophilia, 2012. 18(2): p. 166-174.##Monpoux, F., et al., [Type 2N von Willebrand disease (Normandy)]. Arch Pediatr, 2011. 18(1): p. 45-8.##Baronciani, L. and F. Peyvandi, How we make an accurate diagnosis of von Willebrand disease. Thrombosis Research, 2020. 196: p. 579-589.##Budde, U., Diagnosis of von Willebrand disease subtypes: implications for treatment. Haemophilia, 2008. 14: p. 27-38.##Casonato, A., et al., Identifying carriers of type 2N von Willebrand disease: procedures and significance. Clinical and Applied Thrombosis/Hemostasis, 2007. 13(2): p. 194-200.##Leebeek, F.W. and J.C. Eikenboom, Von Willebrand's disease. New England Journal of Medicine, 2016. 375(21): p. 2067-2080.##Batlle, J., et al., Molecular and clinical profile of von Willebrand disease in Spain (PCM-EVW-ES): Proposal for a new diagnostic paradigm. Thrombosis and haemostasis, 2016. 115(01): p. 40-50.##Borràs, N., et al., Molecular and clinical profile of von Willebrand disease in Spain (PCM-EVW-ES): comprehensive genetic analysis by next-generation sequencing of 480 patients. haematologica, 2017. 102(12): p. 2005.##Caron, C., C. Mazurier, and J. Goudemand, Large experience with a factor VIII binding assay of plasma von Willebrand factor using commercial reagents. British journal of haematology, 2002. 117(3): p. 716-718.##Costa‐Pinto, J., et al., Diagnosis of inherited von Willebrand disease: comparison of two methodologies and analysis of the discrepancies. Haemophilia, 2014. 20(4): p. 559-567.##Hampshire, D.J., et al., Identification and characterisation of mutations associated with von Willebrand disease in a Turkish patient cohort. Thrombosis and haemostasis, 2013. 110(08): p. 264-274.##Taylor, S., et al., Evaluation of an automated screening assay for von Willebrand disease type 2N. Clinical & Laboratory Haematology, 2002. 24(6): p. 369-375.##Veyradier, A., et al., A laboratory phenotype/genotype correlation of 1167 French patients from 670 families with von Willebrand disease: a new epidemiologic picture. Medicine, 2016. 95(11).##Veyradier, A., et al., Validation of the first commercial ELISA for type 2N von Willebrand's disease diagnosis. Haemophilia, 2011. 17(6): p. 944-951.##Zhukov, O., et al., Measurement of von Willebrand factor‐FVIII binding activity in patients with suspected von Willebrand disease type 2N: application of an ELISA‐based assay in a reference laboratory. Haemophilia, 2009. 15(3): p. 788-796.##de Faria, F.C., et al., Von Willebrand Disease Lab Diagnosis. Indian J Hematol Blood Transfus, 2016. 32(2): p. 135-40.##Smith, L.J., Laboratory Diagnosis of von Willebrand Disease. American Society for Clinical Laboratory Science, 2017. 30(2): p. 65-74.##Rizzatti, E.G. and R.F. Franco, Investigação diagnóstica dos distúrbios hemorrágicos. Medicina (Ribeirão Preto), 2001. 34(3/4): p. 237-247.##Barbosa, F.T., R.M.d. Cunha, and L.T. Barbosa, Doença de von Willebrand e Anestesia. Revista Brasileira de Anestesiologia, 2007. 57: p. 315-323.##Comar, S.R., H.S. Danchura, and P.H. Silva, Platelet count: evaluation of manual methodologies and application in the laboratory routine. Revista Brasileira de Hematologia e Hemoterapia, 2009. 31: p. 431-436.##Maleki, A., et al., Determination of normal range of bleeding time in rural and urban residents of Borujerd, Iran: A pilot study. ARYA atherosclerosis, 2012. 8(3): p. 136.##Lombana, M.A., G. Ramos-Ramos, and A.M. Torres, Utilidad del PFA-100 en una población colombiana como método de tamizaje en enfermedad de von Willebrand y trastornos de la función plaquetaria. Revista de Hematología, 2013. 14(2): p. 71-77.##Castaman, G., et al., Validation of a rapid test (VWF-LIA) for the quantitative determination of von Willebrand factor antigen in type 1 von Willebrand disease diagnosis within the European multicenter study MCMDM-1VWD. Thrombosis research, 2010. 126(3): p. 227-231.##Kitchen, S., et al. 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Research and Practice in Thrombosis and Haemostasis, 2018. 2(1): p. e12064.##Sharma, R. and V.H. Flood, Advances in the diagnosis and treatment of Von Willebrand disease. Hematology 2014, the American Society of Hematology Education Program Book, 2017. 2017(1): p. 379-384.##https://doi.org/10.1182/asheducation-2017.1.379##Nichols, W., et al., von Willebrand disease (VWD): evidence‐based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA) 1. Haemophilia, 2008. 14(2): p. 171-232.##Federici, A.B. and M.T. Canciani, Clinical and laboratory versus molecular markers for a correct classification of von Willebrand disease. Haematologica, 2009. 94(5): p. 610.##Casonato, A., et al., Type 2N von Willebrand disease: Characterization and diagnostic difficulties. 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Molecular Pathways of Gliomas Involving RNA-Binding Protein Dynamics 2 2 Gliomas are malignant brain tumors with complicated molecular changes contributing to their aggressiveness and limited treatment choices. RNA-binding proteins are important in post-transcriptional regulation, altering gene expression and impacting glioma formation. In this review article, we will deliberate different molecular pathways of gliomas in which RNA-binding proteins are involved. Studies reveal that a few years ago, RNA-binding proteins had a causative effect on various cancer types such as leukemia, glioblastoma, intestinal, renal, etc. RNA-binding proteins have surfaced as key players in regulating post-transcriptional processes. So, we will discuss in this article Maintaining Glioma Cells Growth, RNA-binding proteins mutations, interacting with deubiquitinating enzymes, RBP Methylation Activates Oncogenic Pathways and RNA-binding proteins in glioma subtypes, highlighting their role in tumorigenesis, invasion, angiogenesis, and therapeutic resistance. 70 83 2024/05/12024/05/112024/03/92024/03/292024/04/22024/03/12023/03/202024/04/11 1403/1/23 2024/06/222024/06/152024/06/132024/05/242024/05/242024/04/192024/04/192024/06/15 1403/3/26 Saman Batool Saman Batool Gomal Centre of Biochemistry and Biotechnology, Gomal University, D.I.Khan, Pakistan. Samanbatool450@gmail.com Hamza Tanveer Hamza Tanveer Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan hamzatanveer.riphah@gmail.com Faisal Naeem Faisal Naeem Department OF Forensic Medicine and Toxicology, Post Graduate Medical Institute, Lahore, Pakistan faisalbandeshah@gmail.com Asma Sarfaraz Asma Sarfaraz Shifa Tameer-e-Millat University of Pharmaceutical Sciences, Islamabad, Pakistan asmasarfraz.0237.scps@gmail.com RNA-binding proteins Gliomas post-transcriptional regulation Oncogenetic pathways RBP Methylation ## ##

Investigating the Dynamic Interplay Between Cellular Immunity and Tumor Cells in the Fight Against Cancer: An Updated Comprehensive Review 2 2 The dynamic interplay between cellular immunity and tumor cells is essential in cancer advancement and response to therapy. This updated, comprehensive review examines the intricate relationship between these components, focusing on the function of different subsets of immune cells in both innate and acquired immunity. A literature search was conducted to identify cytokines involved in tumor cell induction, using keywords such as cytokines, tumor cells, immune cells, and cancer. Relevant articles published between 2003 and 2024 were reviewed, and their data were summarized. The review highlights the different roles of immune cell subsets in coordinating immune responses against tumors. Tumor-associated macrophages (TAMs) And Myeloid-derived suppressor cells (MDSCs) often stimulate cancer growth and evasion of the immune system by suppressing effector cells. Eosinophils and natural killer (NK) cells contribute to tumor surveillance and cytotoxicity, while dendritic cells (DCs) recreate paramount function in T-cell activation and antigen presentation. The complement system and neutrophils contribute to immune regulation and tumor-associated inflammation. T lymphocytes, particularly antigen-presenting cells (APCs) and cytotoxic CD8+ T cells are central to acquired immunity and the anti-tumor immune response. This review highlights how cytokines interact with tumor cells and their role in cancer biology, paving the way for identifying improved prognostic and diagnostic factors. The compiled findings discuss valuable cytokines for a more effective diagnosis of tumors and an accurate prognosis prediction. 84 101 2024/05/12024/05/112024/03/92024/03/292024/04/22024/03/12023/03/202024/04/112024/04/28 1403/2/9 2024/06/222024/06/152024/06/132024/05/242024/05/242024/04/192024/04/192024/06/152024/06/24 1403/4/4 Seyed Ali Aghapour Seyed Ali Aghapour Neonatal & Children᾿s Health Research Center, Golestan University of Medical Sciences, Gorgan, Iran. aghapou@gmail.com Mehdi Torabizadeh Mehdi Torabizadeh Abuzar Children’s Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran torabizadeh@ajums.ac.ir Seyed Sobhan Bahreiny Seyed Sobhan Bahreiny Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran bahsobi@gmail.com Najmaldin Saki Najmaldin Saki Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. najmaldinsaki@gmail.com Mohammad Ali Jalali Far Mohammad Ali Jalali Far Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. alijalilfar@gmail.com Arshid Yousefi-Avarvand Arshid Yousefi-Avarvand Department of Laboratory Sciences, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Arshid.yousefi5@gmail.com Kiana Dost Mohammad Ghasemi Kiana Dost Mohammad Ghasemi Department of Medical Sciences, Lahijan Azad University of Medical Sciences, Lahijan, Gilan, Iran kianaghasemi2023@gmail.com Mojtaba Aghaei Mojtaba Aghaei Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. mojtabaaghaei745@gmail.com Mohammad Mehdi Abolhasani Mohammad Mehdi Abolhasani Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran mahdiabolhasani.20@gmail.com Mohammad Sharif Sharifani Mohammad Sharif Sharifani School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran sharif2022@gmail.com Ehsan Sarbazjoda Ehsan Sarbazjoda Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran ehsan.sarbazjoda@gmail.com Moslem Javidan Moslem Javidan Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran moslemjavidann@gmail.com Cytokines Tumor Cells Cancer Immunity Cells Siegel RL, Miller KD, Wagle NS, Jemal A. 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Impact of Low-Dose Alendronate Therapy on Target Joints in Hemophilia Patients in a Low-Income Country 2 2 Background: Osteoporosis poses a significant clinical challenge for patients with hemophilia (PWH), primarily due to repeated intra-articular bleeding and joint inflammation. The objective of this study was to assess the impact of a combination of calcium-vitamin D and alendronate tablets on reducing the frequency of hemarthrosis in PWH in Lorestan province. Methods: This non-randomized controlled trial involved a total of 118 PWH, out of which 55 patients with severe hemophilia A and B. Each patient underwent two assessments including the frequency and duration of bleeding episodes, and improvement in chronic joint pain, before and after receiving a combination of calcium-vitamin D, alendronate, tranexamic acid, and capsaicin ointment. Variables were measured at six-month intervals (at the beginning and end of the study). The statistical software used was SPSS version 21. Results: The average age of the patients was 33.99 ± 10.67 years. The average number of target joints was 4.18 ± 0.88. A significant correlation was observed between the number of bleeding episodes before and after medication intake (p <0.0001). Similarly, a correlation was found between pre- and post-medication atrophy around the target joint in PWH (p <0.0001). However, no association was detected between joint ankylosis before and after drug administration (p = 0.5). Importantly, there was an improvement in chronic pain post-medication (p <0.0001). Conclusion: The findings suggest that the combination of calcium-vitamin D and low-dose intermittent alendronate can improve hemophilia joint condition. 102 110 2024/05/12024/05/112024/03/92024/03/292024/04/22024/03/12023/03/202024/04/112024/04/282024/04/3 1403/1/15 2024/06/222024/06/152024/06/132024/05/242024/05/242024/04/192024/04/192024/06/152024/06/242024/07/7 1403/4/17 Babak Abdolkarimi Babak Abdolkarimi Lorestan University of Medical Sciences, Khorramabad, Iran b.abdolkarimi@yahoo.com Javad Rostami Javad Rostami Lorestan University of Medical Sciences, Khorramabad, Iran drfrostami@gmail.com Fatemeh Varehzardi Fatemeh Varehzardi Lorestan University of Medical Sciences, Khorramabad, Iran varehzardi.fateme@gmail.com Shadi Tabibian Shadi Tabibian Iranian Comprehensive Hemophilia Care Center, Tehran, Iran Niki Panahi Niki Panahi Health service management, Science and Research branch, Islamic Azad University,Tehran, Iran nikipanahi64@gmail.com Hemophilia Alendronate Hemarthrosis Bisphosphonates Palliative therapy Hoots WK, Rodriguez N, Boggio L, Valentino LA. 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