Many tumours are organised in a hierarchical structure with at its apex a cell that can maintain, establish, and repopulate the tumour—the cancer stem cell. The haematopoietic stem cell (HSC) is the founder cell for all functional blood cells. Like HSCs, the leukaemia stem cells (LSC) are hypothesised to be the leukaemia-initiating cells, which have features of stemness such as self-renewal, quiescence, and resistance to cytotoxic drugs. Immunophenotypically, CD34+CD38− defines HSCs by adding lineage negativity and CD90+CD45RA−. At which stage of maturation the further differentiation is blocked, determines the type of leukaemia, and determines the immunophenotype of the LSC specific to the leukaemia type. No apparent LSC phenotype has been described in lymphoid leukaemia, and it is debated if a specific acute lymphocytic leukaemia-initiating cell is present, as all cells are capable of engraftment in a secondary mouse model. In chronic lymphocytic leukaemia, a B-cell clone is responsible for uncontrolled proliferation, not a specific LSC. In chronic and acute myeloid leukaemia, LSC is described as CD34+CD38− with the expression of a marker that is aberrantly expressed (LSC marker), such as CD45RA, CD123 or in the case of chronic myeloid leukaemia CD26. In acute myeloid leukaemia, the LSC load had prognostic relevance and might be a biomarker that can be used for monitoring and as an addition to measurable residual disease. However, challenges such as the CD34-negative immunophenotype need to be explored.
{"title":"Immunophenotypic features of early haematopoietic and leukaemia stem cells","authors":"Tom Reuvekamp, Costa Bachas, Jacqueline Cloos","doi":"10.1111/ijlh.14348","DOIUrl":"10.1111/ijlh.14348","url":null,"abstract":"<p>Many tumours are organised in a hierarchical structure with at its apex a cell that can maintain, establish, and repopulate the tumour—the cancer stem cell. The haematopoietic stem cell (HSC) is the founder cell for all functional blood cells. Like HSCs, the leukaemia stem cells (LSC) are hypothesised to be the leukaemia-initiating cells, which have features of stemness such as self-renewal, quiescence, and resistance to cytotoxic drugs. Immunophenotypically, CD34+CD38− defines HSCs by adding lineage negativity and CD90+CD45RA−. At which stage of maturation the further differentiation is blocked, determines the type of leukaemia, and determines the immunophenotype of the LSC specific to the leukaemia type. No apparent LSC phenotype has been described in lymphoid leukaemia, and it is debated if a specific acute lymphocytic leukaemia-initiating cell is present, as all cells are capable of engraftment in a secondary mouse model. In chronic lymphocytic leukaemia, a B-cell clone is responsible for uncontrolled proliferation, not a specific LSC. In chronic and acute myeloid leukaemia, LSC is described as CD34+CD38− with the expression of a marker that is aberrantly expressed (LSC marker), such as CD45RA, CD123 or in the case of chronic myeloid leukaemia CD26. In acute myeloid leukaemia, the LSC load had prognostic relevance and might be a biomarker that can be used for monitoring and as an addition to measurable residual disease. However, challenges such as the CD34-negative immunophenotype need to be explored.</p>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"46 5","pages":"795-808"},"PeriodicalIF":2.2,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ijlh.14348","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141753668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ping Guo, Chi Zhang, Dandan Liu, Ziyong Sun, Jun He, Jianbiao Wang
Introduction
This study aims to assess the performance of the platelet count estimation using artificial intelligence technology on the MC-80 digital morphology analyzer.
Methods
Digital morphology analyzer uses two different computational principles for platelet count estimation: based on PLT/RBC ratio (PLT-M1) and estimate factor (PLT-M2). 977 samples with various platelet counts (low, median, and high) were collected. Out of these, 271 samples were immunoassayed using CD61 and CD41 antibodies. The platelet counts obtained from the hematology analyzer (PLT-I and PLT-O), digital morphology analyzer (PLT-M1 and PLT-M2), and flow cytometry (PLT-IRM) were compared.
Results
There was no significant deviation observed before and after verification for both PLT-M1 and PLT-M2 across the analysis range (average bias: −0.845/−0.682, 95% limit of agreement (LOA): −28.675–26.985/−29.420–28.056). When platelet alarms appeared, PLT-M1/PLT-M2 showed the strongest correlation with PLT-IRM than PLT-I with PLT-IRM (r: 0.9814/0.9796 > 0.9601). The correlation between PLT-M1/PLT-M2 and PLT-IRM was strong for samples with interference, such as large platelets or RBC fragments, but relatively weak in small RBCs. The deviation between PLT-M1 and PLT-M2 is related to the number of RBCs. Compared with PLT-I, PLT-M1/PLT-M2 showed higher accuracy for platelet transfusion decisions, especially for samples with low-value PLT.
Conclusion
The novel platelet count estimation on the MC-80 digital morphology analyzer provides high accuracy, especially the reviewed result, which can effectively confirm suspicious platelet count.
{"title":"Evaluation of artificial intelligence-assisted morphological analysis for platelet count estimation","authors":"Ping Guo, Chi Zhang, Dandan Liu, Ziyong Sun, Jun He, Jianbiao Wang","doi":"10.1111/ijlh.14345","DOIUrl":"10.1111/ijlh.14345","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>This study aims to assess the performance of the platelet count estimation using artificial intelligence technology on the MC-80 digital morphology analyzer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Digital morphology analyzer uses two different computational principles for platelet count estimation: based on PLT/RBC ratio (PLT-M1) and estimate factor (PLT-M2). 977 samples with various platelet counts (low, median, and high) were collected. Out of these, 271 samples were immunoassayed using CD61 and CD41 antibodies. The platelet counts obtained from the hematology analyzer (PLT-I and PLT-O), digital morphology analyzer (PLT-M1 and PLT-M2), and flow cytometry (PLT-IRM) were compared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There was no significant deviation observed before and after verification for both PLT-M1 and PLT-M2 across the analysis range (average bias: −0.845/−0.682, 95% limit of agreement (LOA): −28.675–26.985/−29.420–28.056). When platelet alarms appeared, PLT-M1/PLT-M2 showed the strongest correlation with PLT-IRM than PLT-I with PLT-IRM (<i>r</i>: 0.9814/0.9796 > 0.9601). The correlation between PLT-M1/PLT-M2 and PLT-IRM was strong for samples with interference, such as large platelets or RBC fragments, but relatively weak in small RBCs. The deviation between PLT-M1 and PLT-M2 is related to the number of RBCs. Compared with PLT-I, PLT-M1/PLT-M2 showed higher accuracy for platelet transfusion decisions, especially for samples with low-value PLT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The novel platelet count estimation on the MC-80 digital morphology analyzer provides high accuracy, especially the reviewed result, which can effectively confirm suspicious platelet count.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"46 6","pages":"1012-1020"},"PeriodicalIF":2.2,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Landry Seyve, Jean Baptiste Prigent, Caroline Lo Presti, Damien Bédague, Gautier Szymanski, Bénédicte Bulabois, Claire Barro, Raphaël Marlu
{"title":"Effect of emicizumab on activated clotting time performed on i-STAT Alinity analyzer","authors":"Landry Seyve, Jean Baptiste Prigent, Caroline Lo Presti, Damien Bédague, Gautier Szymanski, Bénédicte Bulabois, Claire Barro, Raphaël Marlu","doi":"10.1111/ijlh.14343","DOIUrl":"10.1111/ijlh.14343","url":null,"abstract":"","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"46 6","pages":"1132-1135"},"PeriodicalIF":2.2,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chun-fun Sin, Ka-ping Wong, Chun Wah Siu, Tsz-fu Wong, Hoi-man Wong
Introduction
Specific assays of plasma rivaroxaban level are not always readily available with short turnaround time, which hamper the management of urgent clinical situations. In this study, we aimed to build a predictive formula of plasma rivaroxaban levels from international normalized ratio (INR) value and validated in real world clinical situations.
Methods
Ninety-four patients who were taking rivaroxaban participated in the study. Patients were randomized into testing cohort and validation cohorts. The prediction formula was built from the testing cohort and then validated in validation cohort. The predictive performance was further validated on real-world clinical requests.
Results
The root mean square error (RMSE) of the predictive formula for the testing and validation cohorts were 61.81 and 69.32 ng/mL, respectively. The sensitivity and specificity for the formula to predict the threshold plasma rivaroxaban level of 75 ng/mL were 95% (95% CI: 85.4%–100%) and 87.5% (95% CI: 71.3%–100%), respectively, in real-world clinical situations.
Conclusion
Plasma rivaroxaban level of threshold level of 75 ng/mL can be calculated from prediction formula by INR value with satisfactory accuracy and it can be used to guide the decision for reversal.
{"title":"Utilization of international normalized ratio-derived formula to predict plasma rivaroxaban level—Validation study and real-world experience","authors":"Chun-fun Sin, Ka-ping Wong, Chun Wah Siu, Tsz-fu Wong, Hoi-man Wong","doi":"10.1111/ijlh.14347","DOIUrl":"10.1111/ijlh.14347","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Specific assays of plasma rivaroxaban level are not always readily available with short turnaround time, which hamper the management of urgent clinical situations. In this study, we aimed to build a predictive formula of plasma rivaroxaban levels from international normalized ratio (INR) value and validated in real world clinical situations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Ninety-four patients who were taking rivaroxaban participated in the study. Patients were randomized into testing cohort and validation cohorts. The prediction formula was built from the testing cohort and then validated in validation cohort. The predictive performance was further validated on real-world clinical requests.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The root mean square error (RMSE) of the predictive formula for the testing and validation cohorts were 61.81 and 69.32 ng/mL, respectively. The sensitivity and specificity for the formula to predict the threshold plasma rivaroxaban level of 75 ng/mL were 95% (95% CI: 85.4%–100%) and 87.5% (95% CI: 71.3%–100%), respectively, in real-world clinical situations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Plasma rivaroxaban level of threshold level of 75 ng/mL can be calculated from prediction formula by INR value with satisfactory accuracy and it can be used to guide the decision for reversal.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"46 6","pages":"1101-1108"},"PeriodicalIF":2.2,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ijlh.14347","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhen Li, Jian Zhang, Jingying Han, Qian Wang, Hui Sun, Zhifen Zhang, Tianpu Liu, Yena Che, Jing Wang, Jie Wang, Lulu Xu, Lu Pan, Li Li
Introduction
Aplastic anemia (AA) and hypoplastic myelodysplastic syndrome (MDS-h) are bone marrow failure disease and difficult to distinguish merely by morphological analysis. In this study, we investigated the value of flow cytometry (FCM) in the differential diagnosis of AA and MDS-h.
Methods
We included 822 patients (626 control, 69 AA, 22 MDS-h and 105 dilution patients) from January 2017 to December 2022 for a retrospective study. Bone marrow myeloid progenitor (MP) cell and mature lymphocytes proportions were analyzed by FCM. The ratio of MP cell proportion and mature lymphocytes proportion, MPLR, was calculated. Data were compared by Kruskal–Wallis test. Differential diagnostic efficacy was evaluated by receiver operating characteristic (ROC) curve. Cutoff value was determined by the maximum Youden index.
Results
Bone marrow MP cell proportion and MPLR of MDS-h patients were higher than AA patients. Mature lymphocytes proportion of MDS-h patients was lower than AA patients. Area under ROC curve (AUC of ROC) of MP cell proportion, MPLR and mature lymphocytes proportion to distinguish AA from MDS-h were 0.992, 0.988, and 0.850, respectively. Moreover, MPLR of dilution patients was higher than AA patients but lower than MDS-h patients. The AUC of ROC curves of MPLR to distinguish MDS-h and AA from dilution were 0.854 and 0.871, respectively.
Conclusion
Bone marrow MP cell proportion and MPLR can effectively discriminate AA from MDS-h with similar differential efficacy, which is higher than mature lymphocytes proportion. Moreover, MPLR can evaluate the quality of bone marrow aspirates, which would interfere with the differential diagnosis.
导言：再生障碍性贫血（AA）和低增生性骨髓增生异常综合征（MDS-h）是骨髓衰竭性疾病，仅通过形态学分析难以区分。在这项研究中，我们探讨了流式细胞术（FCM）在 AA 和 MDS-h 鉴别诊断中的价值：我们纳入了2017年1月至2022年12月的822名患者（626名对照组患者、69名AA患者、22名MDS-h患者和105名稀释患者）进行回顾性研究。通过FCM分析骨髓髓系祖细胞（MP）和成熟淋巴细胞的比例。计算骨髓髓系祖细胞和成熟淋巴细胞的比例，即 MPLR。数据比较采用 Kruskal-Wallis 检验。通过接收者操作特征曲线（ROC）评估鉴别诊断效果。根据最大尤登指数确定临界值：结果：MDS-h 患者的骨髓 MP 细胞比例和 MPLR 均高于 AA 患者。MDS-h患者的成熟淋巴细胞比例低于AA患者。MP细胞比例、MPLR和成熟淋巴细胞比例区分AA和MDS-h的ROC曲线下面积（AUC）分别为0.992、0.988和0.850。此外，稀释患者的 MPLR 高于 AA 患者，但低于 MDS-h 患者。MPLR区分MDS-h和AA与稀释的ROC曲线的AUC分别为0.854和0.871：结论：骨髓MP细胞比例和MPLR能有效区分AA和MDS-h，其鉴别效力相似，均高于成熟淋巴细胞比例。此外，MPLR 还能评估骨髓穿刺的质量，这将干扰鉴别诊断。
{"title":"The ratio of bone marrow myeloid progenitor cell proportion to mature lymphocytes proportion can effectively differentiate aplastic anemia and hypoplastic myelodysplastic syndrome and evaluate the quality of bone marrow aspirates","authors":"Zhen Li, Jian Zhang, Jingying Han, Qian Wang, Hui Sun, Zhifen Zhang, Tianpu Liu, Yena Che, Jing Wang, Jie Wang, Lulu Xu, Lu Pan, Li Li","doi":"10.1111/ijlh.14346","DOIUrl":"10.1111/ijlh.14346","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Aplastic anemia (AA) and hypoplastic myelodysplastic syndrome (MDS-h) are bone marrow failure disease and difficult to distinguish merely by morphological analysis. In this study, we investigated the value of flow cytometry (FCM) in the differential diagnosis of AA and MDS-h.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We included 822 patients (626 control, 69 AA, 22 MDS-h and 105 dilution patients) from January 2017 to December 2022 for a retrospective study. Bone marrow myeloid progenitor (MP) cell and mature lymphocytes proportions were analyzed by FCM. The ratio of MP cell proportion and mature lymphocytes proportion, MPLR, was calculated. Data were compared by Kruskal–Wallis test. Differential diagnostic efficacy was evaluated by receiver operating characteristic (ROC) curve. Cutoff value was determined by the maximum Youden index.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Bone marrow MP cell proportion and MPLR of MDS-h patients were higher than AA patients. Mature lymphocytes proportion of MDS-h patients was lower than AA patients. Area under ROC curve (AUC of ROC) of MP cell proportion, MPLR and mature lymphocytes proportion to distinguish AA from MDS-h were 0.992, 0.988, and 0.850, respectively. Moreover, MPLR of dilution patients was higher than AA patients but lower than MDS-h patients. The AUC of ROC curves of MPLR to distinguish MDS-h and AA from dilution were 0.854 and 0.871, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Bone marrow MP cell proportion and MPLR can effectively discriminate AA from MDS-h with similar differential efficacy, which is higher than mature lymphocytes proportion. Moreover, MPLR can evaluate the quality of bone marrow aspirates, which would interfere with the differential diagnosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"46 6","pages":"1077-1083"},"PeriodicalIF":2.2,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. M. Adcock, G. W. Moore, G. W. Kershaw, S. A. L. Montalvao, R. C. Gosselin
This guidance document has been prepared on behalf of the International Council for Standardization in Haematology (ICSH). The aim of the document is to provide guidance and recommendations for the performance and interpretation of activated partial thromboplastin time (APTT) and prothrombin time (PT) plasma mixing tests in clinical laboratories in all regions of the world. The following areas are included in this document: preanalytical, analytical, postanalytical, and quality assurance considerations as they relate to the proper performance and interpretation of plasma mixing tests. The recommendations are based on good laboratory practice, published data in peer-reviewed literature, and expert opinion.
{"title":"International Council for Standardization in Haematology (ICSH) recommendations for the performance and interpretation of activated partial thromboplastin time and prothrombin time mixing tests","authors":"D. M. Adcock, G. W. Moore, G. W. Kershaw, S. A. L. Montalvao, R. C. Gosselin","doi":"10.1111/ijlh.14344","DOIUrl":"10.1111/ijlh.14344","url":null,"abstract":"<p>This guidance document has been prepared on behalf of the International Council for Standardization in Haematology (ICSH). The aim of the document is to provide guidance and recommendations for the performance and interpretation of activated partial thromboplastin time (APTT) and prothrombin time (PT) plasma mixing tests in clinical laboratories in all regions of the world. The following areas are included in this document: preanalytical, analytical, postanalytical, and quality assurance considerations as they relate to the proper performance and interpretation of plasma mixing tests. The recommendations are based on good laboratory practice, published data in peer-reviewed literature, and expert opinion.</p>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"46 5","pages":"777-788"},"PeriodicalIF":2.2,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ijlh.14344","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141621996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>Leukocytosis, defined as an increase in the number of white blood cells (WBC), is a common feature in hospitalized patients. The most common form of leukocytosis is the increase of neutrophilic granulocytes. A profound increase in neutrophilic granulocytes is also known as a leukemoid reaction (LR). Since the first introduction of the term “leukemoid reaction” by Krumbhaar in 1926,<span><sup>1</sup></span> its diagnosis has significantly improved when various laboratory methods were introduced to differentiate LR from malignant granulocytic proliferation. The prognosis for patients with LR relies primarily on their underlying causes; however, the mortality rate remains relatively high.<span><sup>2</sup></span> Therefore, a simple and reproducible method for the initial evaluation of blood, especially when ancillary studies are unavailable, is clinically paramount for improving patient care.</p><p>Different cutoffs have been reported in the literature for defining neutrophilic LR. Some authors have used a cutoff of 25.0 × 10<sup>9</sup> leukocytes/L<span><sup>3</sup></span>, while others have applied higher cutoffs of 40.0 × 10<sup>9</sup>/L, or 50.0 × 10<sup>9</sup>/L.<span><sup>4, 5</sup></span> Regardless of the cutoff, neutrophilic LR shares similar features with profound increases in neutrophils and precursors mimicking chronic leukemia of granulocytic lineage. The increase in immature forms in LR, also known as left-shift, however, is predominantly late forms (segmented neutrophils, band neutrophils) with a minority of intermediate forms (metamyelocytes, myelocytes) and no increase in early forms (promyelocytes, blasts). In addition, neutrophilic LR is usually associated with morphologic features of “toxic changes,” including heavy cytoplasmic granules (toxic granules), Dohle bodies, and cytoplasmic vacuoles. Clinical assessment of patients with potential LR relies heavily on these morphologic features.</p><p>One of the most important differential diagnoses of LR is chronic myeloid leukemia (CML), which may show similar findings when evaluating blood smears. CML is a stem cell neoplasm affecting all three lineages of hematopoietic cells, with the most profound proliferation in the granulocytic lineage. The patients typically present with marked granulocytosis with a predominance of neutrophilic granulocytes and precursors. Eosinophilic and basophilic lineages are also increased but to a lesser degree. CML can be differentiated from LR by several features when evaluating blood smears. CML shows a more prominent left-shift in neutrophilic granulocytes with the entire spectrum of immature forms. Eosinophils and basophils are also increased in CML. The granulocytic cells in CML typically lack the “toxic changes” commonly seen in LR.</p><p>The vast majority of CML and LR can be readily differentiated by a review of blood smears and clinical history. Occasionally, differentiating LR from CML can be challenging on blood smear review due to morph
使用 Microsoft Excel 整理数据，对范围、中位数、均值进行描述性分析，并使用 t 检验进行统计分析。P 值等于或低于 0.01 即为具有统计学意义。CML 患者的年龄从 21 岁到 83 岁不等，中位年龄为 56.5 岁。男女比例为 2.1:1。所有慢性骨髓性白血病患者均在慢性期表现为慢性骨髓性白血病。LR患者的年龄从18岁到90岁不等，中位年龄为61岁。男女比例为 1:1.4。LR的病因是感染（45%）、炎症（43%）和药物（18%）。CML 白细胞计数中位数为 86.75 × 109/L（31.0 × 109-365.1 × 109），而 LR 白细胞计数中位数为 33.5 × 109/L（25.6 × 109- 67.4 × 109）。对 CML 和 LR 病例进行的人工鉴别计数显示，CML 病例的偏骨髓细胞、髓细胞、原髓细胞、囊泡、嗜酸性粒细胞和嗜碱性粒细胞的百分比明显更高。然而，LR 中性粒细胞的百分比明显更高。为了评估白细胞计数在区分 LR 和慢性粒细胞性白血病方面的诊断性能，我们进行了接收者操作特征（ROC）曲线分析。ROC曲线下面积（AUC）为0.92（95% CI：0.85-0.99），显示出良好的鉴别能力。最佳临界值为 45 × 109/L，灵敏度为 0.93，特异度为 0.76，可确保识别出大多数 CML 病例。建议临床使用 45 × 109/L 的临界值来区分 LR 和 CML。然而，由于存在假阴性和假阳性结果，该临界值不能单独使用，应与所有可用的实验室结果结合使用，以进行最准确的评估。这些结果证实，CML 中的粒细胞增多倾向于更深层次的左移，中期和早期粒细胞增多。同时，LR 主要影响晚期患者，分段中性粒细胞增多。此外，在 CML 中更容易看到血泡，而在与感染和炎症相关的 LR 中始终检测不到血泡。CML 和 LR 的带状中性粒细胞计数无明显差异。正如预期的那样，嗜酸性粒细胞和嗜碱性粒细胞在 CML 中作为肿瘤群体的一部分而增加，而细菌感染和慢性疾病相关炎症通常不会影响嗜酸性粒细胞和嗜碱性粒细胞。可以预见的是，单核细胞通常不受这两种实体的影响，而且 CML 和 LR 的单核细胞计数没有明显差异。这项研究为文献提供了 CML 和 LR 中血细胞类别的数值范围和统计数据，可作为执业病理学家的有用指南，也可纳入医学教育的教科书中。该研究的局限性在于样本量较小，且主要是来自一家机构的住院患者，存在选择偏差。未来可能需要进行更大规模、多机构的研究来证实我们的发现。
{"title":"Comparison of blood cell counts in leukemoid reaction and chronic myeloid leukemia: A study using Scopio blood cell counter with statistical analysis","authors":"Alaa S. Hrizat, Jerald Z. Gong","doi":"10.1111/ijlh.14341","DOIUrl":"10.1111/ijlh.14341","url":null,"abstract":"<p>Leukocytosis, defined as an increase in the number of white blood cells (WBC), is a common feature in hospitalized patients. The most common form of leukocytosis is the increase of neutrophilic granulocytes. A profound increase in neutrophilic granulocytes is also known as a leukemoid reaction (LR). Since the first introduction of the term “leukemoid reaction” by Krumbhaar in 1926,<span><sup>1</sup></span> its diagnosis has significantly improved when various laboratory methods were introduced to differentiate LR from malignant granulocytic proliferation. The prognosis for patients with LR relies primarily on their underlying causes; however, the mortality rate remains relatively high.<span><sup>2</sup></span> Therefore, a simple and reproducible method for the initial evaluation of blood, especially when ancillary studies are unavailable, is clinically paramount for improving patient care.</p><p>Different cutoffs have been reported in the literature for defining neutrophilic LR. Some authors have used a cutoff of 25.0 × 10<sup>9</sup> leukocytes/L<span><sup>3</sup></span>, while others have applied higher cutoffs of 40.0 × 10<sup>9</sup>/L, or 50.0 × 10<sup>9</sup>/L.<span><sup>4, 5</sup></span> Regardless of the cutoff, neutrophilic LR shares similar features with profound increases in neutrophils and precursors mimicking chronic leukemia of granulocytic lineage. The increase in immature forms in LR, also known as left-shift, however, is predominantly late forms (segmented neutrophils, band neutrophils) with a minority of intermediate forms (metamyelocytes, myelocytes) and no increase in early forms (promyelocytes, blasts). In addition, neutrophilic LR is usually associated with morphologic features of “toxic changes,” including heavy cytoplasmic granules (toxic granules), Dohle bodies, and cytoplasmic vacuoles. Clinical assessment of patients with potential LR relies heavily on these morphologic features.</p><p>One of the most important differential diagnoses of LR is chronic myeloid leukemia (CML), which may show similar findings when evaluating blood smears. CML is a stem cell neoplasm affecting all three lineages of hematopoietic cells, with the most profound proliferation in the granulocytic lineage. The patients typically present with marked granulocytosis with a predominance of neutrophilic granulocytes and precursors. Eosinophilic and basophilic lineages are also increased but to a lesser degree. CML can be differentiated from LR by several features when evaluating blood smears. CML shows a more prominent left-shift in neutrophilic granulocytes with the entire spectrum of immature forms. Eosinophils and basophils are also increased in CML. The granulocytic cells in CML typically lack the “toxic changes” commonly seen in LR.</p><p>The vast majority of CML and LR can be readily differentiated by a review of blood smears and clinical history. Occasionally, differentiating LR from CML can be challenging on blood smear review due to morph","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"46 6","pages":"1125-1127"},"PeriodicalIF":2.2,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ijlh.14341","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Steven Bruzek, Marisol Betensky, Anthony A. Sochet, Neil A. Goldenberg, Vera Ignjatovic
Introduction
Fibrinolysis is a critical aspect of the hemostatic system, with assessment of fibrinolytic potential being critical to predict bleeding and clotting risk. We describe the method for a novel low-plasma-volume assay of fibrinolytic capacity utilizing the euglobulin fraction (the “modified mini-euglobulin clot lysis assay [ECLA]”), its analytic sensitivity to alterations in key fibrinolytic substrates/regulators, and its initial applications in acute and convalescent disease cohorts.
Methods
The modified mini-ECLA requires 50 μL of plasma, a maximal read time of 3 h (with most results available within 60 min), and is entirely performed in a 96-well microplate. Assay measurements were obtained in a variety of commercial control and deficient plasmas representing clinically relevant hypo- and hyperfibrinolytic states, and in three distinct adolescent cohorts with acute or convalescent illness: critically ill, following endotracheal intubation; acute COVID-19-related illness; and ambulatory, 3 months following a venous thromboembolic event.
Results
In 100% and 75% deficient plasmas, hypofibrinolysis for plasminogen-deficient, fibrinolysis for alpha-2-antiplasmin-deficient, and hyperfibrinolysis for plasminogen activator inhibitor-1-deficient plasmas were observed.
Conclusion
The modified mini-ECLA Clot Lysis Time Ratio (“CLTR”) demonstrated moderate-strength correlations with the Clot Formation and Lysis (CloFAL) assay, is analytically sensitive to altered fibrinolytic states in vitro, and correlates with clinical outcomes in preliminarily-studied patient populations.
{"title":"Methods, precision, and analytical sensitivity of a novel low-plasma-volume assay of fibrinolytic capacity utilizing the euglobulin fraction","authors":"Steven Bruzek, Marisol Betensky, Anthony A. Sochet, Neil A. Goldenberg, Vera Ignjatovic","doi":"10.1111/ijlh.14340","DOIUrl":"10.1111/ijlh.14340","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Fibrinolysis is a critical aspect of the hemostatic system, with assessment of fibrinolytic potential being critical to predict bleeding and clotting risk. We describe the method for a novel low-plasma-volume assay of fibrinolytic capacity utilizing the euglobulin fraction (the “modified mini-euglobulin clot lysis assay [ECLA]”), its analytic sensitivity to alterations in key fibrinolytic substrates/regulators, and its initial applications in acute and convalescent disease cohorts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The modified mini-ECLA requires 50 μL of plasma, a maximal read time of 3 h (with most results available within 60 min), and is entirely performed in a 96-well microplate. Assay measurements were obtained in a variety of commercial control and deficient plasmas representing clinically relevant hypo- and hyperfibrinolytic states, and in three distinct adolescent cohorts with acute or convalescent illness: critically ill, following endotracheal intubation; acute COVID-19-related illness; and ambulatory, 3 months following a venous thromboembolic event.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In 100% and 75% deficient plasmas, hypofibrinolysis for plasminogen-deficient, fibrinolysis for alpha-2-antiplasmin-deficient, and hyperfibrinolysis for plasminogen activator inhibitor-1-deficient plasmas were observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The modified mini-ECLA Clot Lysis Time Ratio (“CLTR”) demonstrated moderate-strength correlations with the Clot Formation and Lysis (CloFAL) assay, is analytically sensitive to altered fibrinolytic states in vitro, and correlates with clinical outcomes in preliminarily-studied patient populations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"46 6","pages":"1092-1100"},"PeriodicalIF":2.2,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Didier Jambou, Noemie Saut, Viviane Queyrel, Anny Appert-Flory, Florence Fischer, Pierre Suchon, Neila De Pooter, Pierre Toulon
Introduction
G20210A (c.*97G>A) prothrombin gene variant, found in white population has been associated with an increased risk of venous thromboembolism (VTE). Other rare polymorphisms in F2 gene (C20209T) have been reported, more rare and touching black people, but its potential association with VTE remain uncertain.
Methods
About a 69 years-old Caucasian woman presenting an unprovoked deep venous thrombosis of the leg, we analyzed retrospectively 25.000 thrombophilia tests on a 11-year period of time (2007–2018), at Nice and Marseille University Hospitals, and performed extensive review of the literature.
Results
Genetic determination included a similar PCR protocol and sequencing. Twenty-one heterozygous cases out of 25.585 determinations (0.08%) was found. The C20209T mutation detected in our Caucasian patient is rare, with a frequency that differed from what was reported in the previous literature, mainly in non-Caucasian patients (Africans, Africans-Americans, and Caribbeans). One hundred and thirteen patients with this mutation have been described in the literature, of which only one homozygous.
Conclusion
This study is the most important on C20209T mutation performed at present, allowing to precise its frequency and its potential role in venous thromboembolism.
{"title":"F2c.*C20209T mutation in patients with a history of thrombosis: A case report, retrospective 2 site-results and review of the literature","authors":"Didier Jambou, Noemie Saut, Viviane Queyrel, Anny Appert-Flory, Florence Fischer, Pierre Suchon, Neila De Pooter, Pierre Toulon","doi":"10.1111/ijlh.14312","DOIUrl":"10.1111/ijlh.14312","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>G20210A (c.*97G>A) prothrombin gene variant, found in white population has been associated with an increased risk of venous thromboembolism (VTE). Other rare polymorphisms in F2 gene (C20209T) have been reported, more rare and touching black people, but its potential association with VTE remain uncertain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>About a 69 years-old Caucasian woman presenting an unprovoked deep venous thrombosis of the leg, we analyzed retrospectively 25.000 thrombophilia tests on a 11-year period of time (2007–2018), at Nice and Marseille University Hospitals, and performed extensive review of the literature.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Genetic determination included a similar PCR protocol and sequencing. Twenty-one heterozygous cases out of 25.585 determinations (0.08%) was found. The C20209T mutation detected in our Caucasian patient is rare, with a frequency that differed from what was reported in the previous literature, mainly in non-Caucasian patients (Africans, Africans-Americans, and Caribbeans). One hundred and thirteen patients with this mutation have been described in the literature, of which only one homozygous.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study is the most important on C20209T mutation performed at present, allowing to precise its frequency and its potential role in venous thromboembolism.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"46 5","pages":"894-898"},"PeriodicalIF":2.2,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ijlh.14312","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141556256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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