International journal of laboratory hematology最新文献

Hematology laboratories have traditionally monitored hemophilia replacement therapy by measuring coagulation factors before and after infusion. However, new drugs that do not rely on the replacement of the deficient factor require new approaches to laboratory monitoring, as factor VIII (FVIII) or factor IX (FIX) assays are no longer adequate. Non-factor therapies come in many different forms, that have one thing in common: they all increase thrombin generation. Their main adverse effect is thrombosis which may occur when too much thrombin is formed. This is the perfect mirror image of anticoagulant treatment, which always diminishes the amount of thrombin formed and has bleeding as its main adverse effect. Thrombin-forming capacity is decreased in congenital bleeding disorders and increased in prothrombotic conditions, indicating it governs bleeding and thrombosis. Therefore, the thrombin generation assay (TGA) is a logical tool for monitoring non-factor therapies, offering a comprehensive assessment of hemostatic balance. TGA identifies patients with severe bleeding, helps to optimize bypassing therapy, and detects hypercoagulability, making it ideal for guiding and monitoring hemophilia treatment with non-factor therapies. It also assesses the efficacy and safety of combined therapies, including non-factor therapies with bypassing agents or FVIII/FIX concentrates. The purpose of this paper is to review the current state of knowledge regarding the use of TGA to monitor novel hemophilia therapies. It will address controversies, limitations, and knowledge gaps related to the integration of TGA into personalized medicine in routine clinical practice.

Background: A wide variety of laboratory hemostasis tests is available, but the majority is plasma-based, static and unable to assess platelet function and fibrin formation simultaneously. The Total Thrombus-Formation Analysis System (T-TAS) is a microchip-based flow chamber system that simulates in vivo conditions for evaluating whole blood thrombogenicity.

Aim: A comprehensive overview of its applicability in different thrombosis and hemostasis related clinical situations is lacking and therefore this scoping review was performed.

Materials & methods: A literature search was done using the electronic databases PubMed, Scopus and Embase on January 7, 2024. Original studies assessing the usefulness of the T-TAS in thrombosis and hemostasis related clinical situations were eligible for this scoping review.

Results: A total of 28 studies were included; six studies investigating the role of the T-TAS in congenital bleeding disorders, five studies using the T-TAS to assess 1-year bleeding risk in patients on antiplatelet or anticoagulant medications, four studies investigating the effects of thrombocytopenia and hemodialysis on thrombus formation as measured by the T-TAS, 11 studies testing the applicability of the T-TAS in the monitoring of anticoagulant and antiplatelet therapies and eventually two studies on the ability of the T-TAS to assess the thrombogenicity in different disease entities.

Discussion & conclusion: The T-TAS method is an interesting technology that mimics the complex biological coagulation process using shear forces, creating a "blood vessel component on a chip". More research is needed, but it could eventually function as a screening test for platelet function and coagulation. Moreover, it could be used to detect the presence of anticoagulant and/or antiplatelet medication.

Introduction: The first-step in diagnosis of myelodysplastic neoplasms (MDS) is essentially based on bone marrow cytomorphology. However, cytomorphology of MDS is often a difficult exercise, subject to inter-operator variability. Our study aims to evaluate whether the combination of two dysplasia scores, the extended Ogata score and the MDS-CBC score, could improve the screening of MDS patients among patients with chronic cytopenia.

Methods: Extended Ogata score and MDS-CBC score have been measured on a retrospective cohort of 63 patients with a clinical suspicion of MDS based on the presence of cytopenia. Among these patients, 33 patients were diagnosed as MDS (MDS group) and 30 patients were diagnosed with another cause of cytopenia (non-MDS cytopenic control group).

Results: Our results show excellent performance of the combined scores in predicting MDS when the two scores are concordant: positive predictive value (PPV) = 96% and negative predictive value (NPV) = 92%. In comparison, in the same cohort, extended Ogata score alone showed a PPV = 90% and NPV = 79%, MDS-CBC score alone showed a PPV = 85% and NPV = 86%.

Conclusion: For the first time, our results show that the combination of these two dysplasia scores constitutes a useful and rapid tool for the assessment of dysplasia associated with MDS. In the MDS diagnostic process, the use of combined scores could constitute a valuable tool to enable early strong prediction of MDS in cytopenic patients and to target patients who initially require additional genetic assays.

Objective: In this study, clinical bioinformatics analysis was used to identify potential biomarkers of acute myeloid leukemia (AML) occurrence and development, drug resistance, and poor prognosis to provide a theoretical basis for the treatment of AML.

Methods: On the basis of the TCGA, GEO, and GTEx databases, an AML secondary database was established, and differential expression analysis and WGCNA were carried out to identify genes related to the prognosis of AML patients. Survival analysis was carried out for internal verification of key genes, and GEO data were used for external verification to obtain core genes related to prognosis. For differentially expressed genes, the EpiMed platform independently developed by the team was used for drug prediction.

Results: A total of 36 overlapping genes were obtained via difference analysis and WGCNA. Enrichment analysis revealed that the overlapping genes were associated with neutrophil activation, transcription dysregulation, AML, apoptosis, and other biological indicators. A protein interaction network was constructed for NCOA4, ACSL4, DPP4, ATL1, MT1G, ALOX15, and SLC7A11, which are key genes. Survival analysis revealed that NCOA4, ACSL4, DPP4, and ATL1 significantly affected the survival of patients with AML. The GSE142698 dataset verified that MPO, BCL2A1, and STMN1 had a statistically significant impact on the survival of AML patients.

Conclusion: NCOA4, ACSL4, DPP4, and ATL1 may be potential biomarkers related to the survival and prognosis of patients with AML, and the calcineurin signaling pathway is associated with the risk of vascular fragility in AML patients, which can provide a reference for further research and optimization of treatment regimens.

Background: Platelets, besides being traditionally associated with hemostasis, have been recently positioned as immune cells. Alterations in platelet number and function have been reported in some viral infections. Zika virus (ZIKV) and Dengue virus (DENV) are arboviruses that encode for a non-structural protein 1 (NS1). NS1 is mainly involved in the viral replication process and can also be secreted by infected cells and has been associated with immune response evasion. The assessment of platelet reactivity against these viral agents and their proteins, through the use of different innovative technologies such as flow cytometry (FC), atomic force microscopy (AFM), and quartz crystal microbalance (QCM), will allow further study of the pathophysiology of these emerging diseases.

Aim: The aim of this study was to assess platelet reactivity to ZIKV and DENV NS1 protein through the use of FC, AFM, and QCM.

Methods: Platelet-rich plasma (PRP) was stimulated with ZIKV and DENV NS1 protein in individual assays. The expression of P-selectin and the activity of the glycoprotein IIb-IIIa, platelet activation markers, were assessed by FC, morphological changes were assessed by AFM, and interaction between NS1 protein and platelet were evaluated by QCM.

Results: An increased expression of P-selectin and GP IIb-IIIa activity (p < 0.001) was observed when PRP was stimulated with ZIKV and DENV NS1 proteins. AFM images showed an increase in cell size and the appearance of pseudopods upon stimulation with the viral proteins. QCM results showed a significant increase in the oscillation frequency of the quartz precoated with ZIKV or DENV NS1 when PRP was injected (p < 0.001).

Conclusion: FC, AFM, and QCM are techniques that can be used in the study of platelet response to viral structures such as NS1 protein, broadening the range of existing methodologies in the study of these cells. It is imperative to study platelets in arboviral infections to better understand their involvement in these diseases.

Introduction: The link between DNA repair gene polymorphisms and cancer susceptibility has gained significant attention. Thus, we investigated the impact of base excision repair (BER) gene polymorphisms on acute myeloid leukemia (AML) risk and pathogenesis.

Methods: In total, 106 patients with AML and 191 healthy controls were included in the study, wherein polymorphisms in four BER genes (APEX1, MUTYH, OGG1, and XRCC1) were examined.

Results: Notably, the APEX1-656 T>G polymorphism exhibited a significant association with AML risk in the recessive (TT vs. TG + GG) (p = 0.046) and co-dominant models (TT vs. GG) (p = 0.02). Assessing APEX1 expression levels, APEX1 expression was elevated in the bone marrow of patients with AML compared with that in controls (p = 0.02). Subsequently, we compared the percentages of CD34+ cells between the APEX1 high or low expression groups, revealing a significant difference (high vs. low = 29.9% vs. 11.5%, p = 0.01). Additionally, we observed reduced APEX1 expression in HL60 cells differentiated with all-trans retinoic acid (p < 0.001). We hypothesized that APEX1 expression could correlate with stemness and analyzed its expression in stem and differentiated cells.

Conclusions: In the GSE48558 dataset, AML cells and normal CD34+ cells expressed APEX1 at higher levels than did granulocytes (p < 0.01). Functional experiments revealed that APEX1 knockdown led to a reduction in AML cell proliferation. These findings indicated that APEX1 polymorphisms were a potential risk factor for AML and highlighted the important role of APEX1 in regulating AML cell differentiation and proliferation.