Blood Diseases and In vitro Methods and Technologies
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Abstract
In vitro diagnostics, which appraise bodily functions or illnesses by extra-corporeal examination of materials like tissue and blood, have become increasingly important in our daily lives due to increased health consciousness and the advancement of new technology. Moreover, in addition to therapeutic applications, in-vitro diagnostics may also be used to screen for and prevent diseases. Laboratory methods and techniques have changed and have forwarded movements and developed. Laboratory hematology has a role in all aspects of patient care, from basic screening to more complex investigations in third-party care services. It also includes non-laboratory services like bone marrow transplantation and blood transfusion. Diagnosis of hematology patients correlated to the target and material that they want to find and rectify the reasons of illness, such as molecular assays that tested genetic materials and macromolecules, biochemistry assays that detected the metabolic disorders, which differentiated factors by biochemical properties and interactions, and biophysical assays that utilized the light and microscopically analyzed tools for tests. In this systematic analysis, the contemporary published articles that discuss the diagnosis of hematological diseases and demonstrate the factors of diseases that correlate with the Laboratory methods of assays. And want to indicate the correlation between the factor of illness in diagnosis analysis and laboratory methods and techniques that are utilized in diagnosis.
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Vitzthum F, Behrens F, Anderson NL, Shaw JH. Proteomics: from basic research to diagnostic application. A review of requirements & needs. J Proteome Res. 2005;4(4):1086–97. Available from: https://doi.org/10.1021/pr050080b
Lippi G, Plebani M, Favaloro EJ, Trenti T. Laboratory testing in pharmacies. Clin Chem Lab Med. 2010;48(7):943–53. Available from: https://doi.org/10.1515/cclm.2010.184
Mackie IJ, d’Onofrio G. Recent developments in the International Journal of Laboratory Hematology. Int J Lab Hematol. 2022;44(S1):4–5. Available from: https://doi.org/10.1111/ijlh.13858?urlappend=%3Futm_source%3Dresearchgate.net%26medium%3Darticle
Ozaslan M, Oguzkan SB. The use of molecular biology methods in evaluating hematologic diseases. Eurasia Proc Sci Technol Eng Math. 2020;9:18–22. Available from: https://dergipark.org.tr/en/download/article-file/1174342
Boender J, Kruip MJHA, Leebeek FWG. A diagnostic approach to mild bleeding disorders. J Thromb Haemost. 2016;14(8):1507–16. Available from: https://doi.org/10.1111/jth.13368
Pavlou EG, Georgatzakou HT, Fortis SP, Tsante KA, Tsantes AG, Nomikou EG, et al. Coagulation abnormalities in renal pathology of chronic kidney disease: the interplay between blood cells and soluble factors. Biomolecules. 2021;11(9). Available from: https://doi.org/10.3390/biom11091309
Murphree CR, Nguyen NN, Raghunathan V, Olson SR, DeLoughery T, Shatzel JJ. Diagnosis and management of hereditary haemochromatosis. Vox Sang. 2020;115(4):255–62. Available from: https://doi.org/10.1111/vox.12896
Greinacher A, Pecci A, Kunishima S, Althaus K, Nurden P, Balduini CL, et al. Diagnosis of inherited platelet disorders on a blood smear: a tool to facilitate worldwide diagnosis of platelet disorders. J Thromb Haemost. 2017;15(7):1511–21. Available from: https://doi.org/10.1111/jth.13729
Mailer RK, Kuta P, Renné T. An update on safe anticoagulation. Hamostaseologie. 2022;42(1):65–72. Available from: https://doi.org/10.1055/a-1717-7958
Mensah C, Sheth S. Optimal strategies for carrier screening and prenatal diagnosis of α- and β-thalassemia. Hematology Am Soc Hematol Educ Program. 2021;2021(1):607–13. Available from: https://doi.org/10.1182/hematology.2021000296
Lauzon-Young C, Silva A, Sadikovic B. Epigenomic insights and computational advances in hematologic malignancies. Mol Cytogenet. 2025;18(1):9. Available from: https://doi.org/10.1186/s13039-025-00712-9
Rizk SH. Challenges to laboratory hematology practice: Egypt perspective. Int J Lab Hematol. 2018;40(Suppl 1):126–36. Available from: https://doi.org/10.1111/ijlh.12834
Dobson CM. Biophysical techniques in structural biology. Annu Rev Biochem. 2019;88:25–33. Available from: https://doi.org/10.1146/annurev-biochem-013118-111947
Elmlund D, Elmlund H. Cryogenic electron microscopy and single-particle analysis. Annu Rev Biochem. 2015;84(1):499–517. Available from: https://doi.org/10.1146/annurev-biochem-060614-034226
Mandala VS, Williams JK, Hong M. Structure and dynamics of membrane proteins from solid-state NMR. Annu Rev Biophys. 2018;47:201–22. Available from: https://doi.org/10.1146/annurev-biophys-070816-033712
Mehmood S, Allison TM, Robinson CV. Mass spectrometry of protein complexes: from origins to applications. Annu Rev Phys Chem. 2015;66:453–74. Available from: https://doi.org/10.1146/annurev-physchem-040214-121732
Baddeley D, Bewersdorf J. Biological insight from super-resolution microscopy: what we can learn from localization-based images. Annu Rev Biochem. 2018;87:965–89. Available from: https://doi.org/10.1146/annurev-biochem-060815-014801
Ha T, Tinnefeld P. Photophysics of fluorescent probes for single-molecule biophysics and super-resolution imaging. Annu Rev Phys Chem. 2012;63:595–617. Available from: https://doi.org/10.1146/annurev-physchem-032210-103340
Browne WJ, North AC, Phillips DC, Brew K, Vanaman TC, Hill RL. A possible three-dimensional structure of bovine alpha-lactalbumin based on that of hen’s egg-white lysozyme. J Mol Biol. 1969;42(1):65–86. Available from: https://doi.org/10.1016/0022-2836(69)90487-2
Huang PS, Boyken SE, Baker D. The coming of age of de novo protein design. Nature. 2016;537(7620):320–7. Available from: https://doi.org/10.1038/nature19946
Zhuang C, Gould JE, Enninful A, Shao S, Mak M. Biophysical and mechanobiological considerations for T-cell-based immunotherapy. Trends Pharmacol Sci. 2023;44(6):366–78. Available from: https://doi.org/10.1016/j.tips.2023.03.007
Dror RO, Dirks RM, Grossman JP, Xu H, Shaw DE. Biomolecular simulation: a computational microscope for molecular biology. Annu Rev Biophys. 2012;41:429–52. Available from: https://doi.org/10.1146/annurev-biophys-042910-155245
Zini G, Barbagallo O, Scavone F, Béné MC. Digital morphology in hematology diagnosis and education: the experience of the European LeukemiaNet WP10. Int J Lab Hematol. 2022;44(S1):37–44. Available from: https://doi.org/10.1111/ijlh.13908
Sasada K, Yamamoto N, Masuda H, Tanaka Y, Ishihara A, Takamatsu Y, et al. Inter-observer variance and the need for standardization in the morphological classification of myelodysplastic syndrome. Leuk Res. 2018;69:54–9. Available from: https://doi.org/10.1016/j.leukres.2018.04.003
Mufti GJ, Bennett JM, Goasguen J, Bain BJ, Baumann I, Brunning R, et al. Diagnosis and classification of myelodysplastic syndrome: International Working Group on Morphology of Myelodysplastic Syndrome consensus proposals for the definition and enumeration of myeloblasts and ring sideroblasts. Haematologica. 2008;93(11):1712–7. Available from: https://doi.org/10.3324/haematol.13405
Goasguen JE, Bennett JM, Bain BJ, Brunning RD, Vallespí MT, Tomonaga M, et al. Quality control initiative on the evaluation of the dysmegakaryopoiesis in myeloid neoplasms: difficulties in the assessment of dysplasia. Leuk Res. 2016;45:75–81. Available from: https://doi.org/10.1016/j.leukres.2016.04.009
Goasguen JE, Bennett JM, Bain BJ, Brunning R, Zini G, Vallespi MT, et al. The role of eosinophil morphology in distinguishing between reactive eosinophilia and eosinophilia as a feature of a myeloid neoplasm. Br J Haematol. 2020;191(3):497–504. Available from: https://doi.org/10.1111/bjh.17026
World Health Organization. Anaemia in women and children. Geneva: World Health Organization; 2021. Available from: https://www.who.int/data/gho/data/themes/topics/anaemia_in_women_and_children
Briggs C, Culp N, Davis B, d’Onofrio G, Zini G, Machin SJ. ICSH guidelines for the evaluation of blood cell analysers, including those used for differential leucocyte and reticulocyte counting. Int J Lab Hematol. 2014;36(6):613–27. Available from: https://doi.org/10.1111/ijlh.12201
Zini G, d’Onofrio G, Erber WN, Lee SH, Nagai Y, Basak GW, et al. 2021 update of the 2012 ICSH recommendations for identification, diagnostic value, and quantitation of schistocytes: impact and revisions. Int J Lab Hematol. 2021;43(6):1264–71. Available from: https://doi.org/10.1111/ijlh.13682
Fuentes-Arderiu X, García-Panyella M, Dot-Bach D. Between-examiner reproducibility in manual differential leukocyte counting. Accred Qual Assur. 2007;12:643–5. Available from: https://doi.org/10.1515/cclm.2009.014
Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J. WHO classification of tumours of haematopoietic and lymphoid tissues. International Agency for Research on Cancer; 2017. Available from: https://publications.iarc.who.int/Book-And-Report-Series/Who-Classification-Of-Tumours/WHO-Classification-Of-Tumours-Of-Haematopoietic-And-Lymphoid-Tissues-2017
John MB. Morphological classification of the myelodysplastic syndromes: how much more education of diagnosticians is necessary? Haematologica. 2013;98(4):490–1. Available from: https://doi.org/10.3324/haematol.2013.084418
Koutsi A, Vervesou EC. Diagnostic molecular techniques in haematology: recent advances. Ann Transl Med. 2018;6(12):242. Available from: https://doi.org/10.21037/atm.2018.05.30
Harper SL, Sriswasdi S, Tang HY, Gaetani M, Gallagher PG, Speicher DW. The common hereditary elliptocytosis-associated α-spectrin L260P mutation perturbs erythrocyte membranes by stabilizing spectrin in the closed dimer conformation. Blood. 2013;122(17):3045–53. Available from: https://doi.org/10.1182/blood-2013-02-487702
Wu Y, Liao L, Lin F. The diagnostic protocol for hereditary spherocytosis—2021 update. J Clin Lab Anal. 2021;35(12):e24034. Available from: https://doi.org/10.1002/jcla.24034
Pepeler MS, Falay M, Aydın MS, Parmaksız A, Keskin EY, Alanoğlu G, et al. Eosin-5′-maleimide (EMA)-binding assay as a diagnostic method of hereditary spherocytosis. Turk J Biochem. 2025. Available from: https://doi.org/10.1515/tjb-2025-0040?urlappend=%3Futm_source%3Dresearchgate.net%26medium%3Darticle
Shih YH, Huang YC, Lin CY, Lin HY, Kuo SF, Lin JS, et al. A large family of hereditary spherocytosis and a rare case of hereditary elliptocytosis with a novel SPTA1 mutation underdiagnosed in Taiwan: a case report and literature review. Medicine. 2023;102(4):e32708. Available from: https://doi.org/10.1097/md.0000000000032708
Laithaisong S, Muisuk K, Komwilaisak P, Laoaroon N, Suwannaying K, Rattanathongkom A, et al. Novel ANK1 mutation in hereditary spherocytosis in a northeastern Thai patient: a case report. Med Rep. 2025;13:100239. Available from: https://doi.org/10.1016/j.hmedic.2025.100239
Andolfo I, Russo R, Gambale A, Iolascon A. Hereditary stomatocytosis: an underdiagnosed condition. Am J Hematol. 2018;93(1):107–21. Available from: https://doi.org/10.1002/ajh.24929
Chonat S, Risinger M, Sakthivel H, Niss O, Rothman JA, Hsieh L, et al. The spectrum of SPTA1-associated hereditary spherocytosis. Front Physiol. 2019;10:815. Available from: https://doi.org/10.3389/fphys.2019.00815
Li X, Zhang T, Li X, Wang L, Li Q, Liu Q, et al. Identification of a novel SPTB gene splicing mutation in hereditary spherocytosis: a case report and diagnostic insights. Front Genet. 2025;15. Available from: https://doi.org/10.3389/fgene.2024.1522204
Han E, Kim A, Park J, Kim M, Kim Y, Han K, et al. Spectrin Tunis (Sp alpha (I/78)) in a Korean family with hereditary elliptocytosis. Ann Lab Med. 2013;33(5):386–9. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC3756249/
Sun X, Zeng Q, He R, Zhou L, Hou Q. Frameshift mutation in the EPB41 gene with hereditary elliptocytosis. Indian J Hematol Blood Transfus. 2024:1–2. Available from: https://doi.org/10.1007/s12288-024-01868-x
Onat M, Kavak EC, Akcabay C, Malkan Z, Kaya T, Batmaz I, et al. Evaluation of transcutaneous bilirubin levels in healthy and preeclamptic pregnancies: a pilot study. BMC Pregnancy Childbirth. 2025;25(1):764. Available from: https://doi.org/10.1186/s12884-025-07878-5
Trabelsi N, Bouguerra G, Haddad F, Ouederni M, Darragi I, Boudrigua I, et al. Biochemical, cellular, and proteomic characterization of hereditary spherocytosis among Tunisians. Cell Physiol Biochem. 2021;55(1):117–29. Available from: https://doi.org/10.33594/000000333
Bernhardt I, Kaestner L. Historical view and some unsolved problems in red blood cell membrane research. 2025. Available from: https://doi.org/10.31083/fbl25331
Al-Rawaf HA, Gabr SA, Iqbal A, Alghadir AH. Circulating microRNAs and hepcidin as predictors of iron homeostasis and anemia among school children: a biochemical and cross-sectional survey analysis. Eur J Med Res. 2023;28(1):595. Available from: https://doi.org/10.1186/s40001-023-01579-5
Huibers MHW, Calis JC, Allain TJ, Coupland SE, Phiri C, Phiri KS, et al. A possible role for hepcidin in the detection of iron deficiency in severely anaemic HIV-infected patients in Malawi. PLoS One. 2020;15(2):e0218694. Available from: https://doi.org/10.1371/journal.pone.0218694
Stojkovic Lalosevic M, Toncev L, Stankovic S, Dragasevic S, Stojkovic S, Jovicic I, et al. Hepcidin is a reliable marker of iron deficiency anemia in newly diagnosed patients with inflammatory bowel disease. Dis Markers. 2020;2020:8523205. Available from: https://doi.org/10.1155/2020/8523205
Zhang JY, Wang J, Lu Q, Tan M, Wei R, Lash GE. Iron stores at birth in a full-term normal birth weight birth cohort with a low level of inflammation. Biosci Rep. 2020;40(12). Available from: https://doi.org/10.1042/bsr20202853
Chatterjee P, Mohammadi M, Goozee K, Shah TM, Sohrabi HR, Dias CB, et al. Serum hepcidin levels in cognitively normal older adults with high neocortical amyloid-β load. J Alzheimers Dis. 2020;76(1):291–301. Available from: https://doi.org/10.3233/jad-200162
Singh A, Pandey HC, Chaudhary R. Establishment of normal reference range of serum hepcidin in Indian blood donors. Asian J Transfus Sci. 2023;17(1):1–6. Available from: https://doi.org/10.4103/ajts.ajts_7_22
Tarancon-Diez L, Iriarte-Gahete M, Sanchez-Mingo P, Perez-Cabeza G, Romero-Candau F, Pacheco YM, et al. Real-world experience of intravenous iron sucrose supplementation and dynamics of soluble transferrin receptor and hepcidin in a Spanish cohort of absolute iron-deficient patients. Biomed Pharmacother. 2023;167:115510. Available from: https://doi.org/10.1016/j.biopha.2023.115510
Kali A, Charles MV, Seetharam RS. Hepcidin – a novel biomarker with changing trends. Pharmacogn Rev. 2015;9(17):35–40. Available from: https://doi.org/10.4103/0973-7847.156333
Rusch JA, van der Westhuizen DJ, Gill RS, Louw VJ. Diagnosing iron deficiency: controversies and novel metrics. Best Pract Res Clin Anaesthesiol. 2023;37(4):451–67. Available from: https://doi.org/10.1016/j.bpa.2023.11.001
Nemeth E, Ganz T. Hepcidin and iron in health and disease. Annu Rev Med. 2023;74:261–77. Available from: https://doi.org/10.1146/annurev-med-043021-032816
van der Staaij H, Donker AE, Bakkeren DL, Salemans J, Mignot-Evers LAA, Bongers MY, et al. Transferrin saturation/hepcidin ratio discriminates TMPRSS6-related iron refractory iron deficiency anemia from patients with multi-causal iron deficiency anemia. Int J Mol Sci. 2022;23(3). Available from: https://doi.org/10.3390/ijms23031917