International journal of laboratory hematology最新文献

Hematopathology workflows are complex, since they include numerous data points necessary for guiding further testing, diagnosis, and patient management. The workflows start with complete blood cell counts, with subsequent morphologic evaluation of peripheral blood (PB) and bone marrow (BM). Digital pathology has the potential to revolutionize PB and BM assessment through the implementation of artificial intelligence for assisted and automated evaluation, but there remain major hurdles toward this ultimate goal, such as lack of regulatory oversight, data standardization, insufficient knowledge and training, and resistance to change, among others. This article reviews the current state of digitalization in the hematopathology practice, recent research using machine learning models for automated specimen analysis, outlines the advantages and barriers facing clinical implementation of artificial intelligence, and offers prospective artificial intelligence-driven clinical workflows for efficient and comprehensive clinical workup.

Digital pathology (DP) has evolved alongside other technical advances, transforming our daily lives and diagnostic medicine. It is likely that, as in other areas of life, science, and medicine, the overall level of digitization will continue to rise, along with an increasing number of groups implementing DP. This review explores the clinical DP ecosystem with a focus on hematology and hematopathology, addressing the benefits of DP, such as improved workflow efficiency, remote practice, enhanced collaboration, and integration of artificial intelligence tools. Several challenges and pitfalls are also highlighted, such as technical scanner challenges, image management system issues, IT infrastructure, regulations, and the critical (and expensive) topic of data storage, and retrieval for DP. We also propose a roadmap for the successful implementation of DP, designed to support institutions of all sizes to make the transition to DP. This roadmap emphasizes well-thought-out, strategic planning and aims to ensure that organizations and individuals considering a switch to DP are able to deliver meaningful benefits to pathologists, health systems, providers, and most importantly, patients.

Hematologic emergencies are urgent health conditions which result in significant mortality and morbidity unless timely therapeutic measures are taken. Therapeutic success depends on their timely and accurate recognition by hematology laboratory services. This review highlights the laboratory's role in identifying conditions associated with increased schistocytes (thrombotic microangiopathies) and acute promyelocytic leukemia. Their detection based on the routine laboratory and morphology methods should trigger appropriate additional laboratory workup including molecular tests, flow cytometry, etc. Hematology laboratory professionals should be skilled to recognize these emergencies and recommend additional workup, playing a critical role in the timely diagnosis and management of life-threatening conditions.

The recent fifth edition WHO classification and ICC classification systems have moved further toward genetically defined classifications of acute leukemias. Both now recognize myelodysplasia-related (MR) mutations as defining of MDS-related AML (AML-MR). Acute leukemias of ambiguous lineage (ALAL) are a heterogenous group of acute leukemias characterized by leukemic blasts that either express markers of multiple lineages, mixed phenotype acute leukemia (MPAL), or too few to be assigned a definitive lineage, acute undifferentiated leukemia (AUL). However, the recent classifications are unclear on how ALALs should be categorized in the presence of MR mutations. In short, the current recommendations are to classify cases that are immunophenotypically consistent with ALAL but harbor MR cytogenetics or mutations as AML-MR. Due to their rarity, investigations into the genetic basis of ALAL are limited but show great heterogeneity in their mutational landscapes. Data on the frequencies and significance of MR mutations in ALAL is particularly scant. Our comprehensive review of the literature reporting on the genetic landscapes of MPAL and AUL shows that a significant proportion of MPAL and AUL cases, ~32% and ~59% on average respectively, may harbor one or more mutations in MR genes, with mutations in RUNX1 and ASXL1 among the most common. Additional research is needed into the clinical, immunophenotypic, and genetic characteristics of ALAL to aid in refining classification and to support therapeutic decision making.

Sickle cell disease (SCD) is one of the most frequent monogenic diseases worldwide and a highly heterogeneous and complex disease. SCD care carries several challenges. This includes early and accurate diagnosis as well as optimal red blood cell transfusion matching in this population carrying a high risk of alloimmunization. For decades, molecular biology has used hemoglobin and SCD as models for the development of several molecular tools. Such tools can now be used for various aspects of SCD care. Molecular diagnosis is notably the root of noninvasive prenatal testing. In postnatal diagnosis, including newborn screening, molecular approaches can overcome several limitations of protein-based methods. Simple approaches such as polymerase chain reaction can be used as a high-throughput and low-cost screening test. Moreover, combining sequence and deletion analyses allows for a comprehensive study of the β-globin locus, resolving complex cases. In transfusion care, genotyping for blood group determination has been shown to be more accurate compared to protein-based serological testing. Future development of molecular testing in SCD includes their use as prognostic tools and recent molecular diagnosis approaches. However, despite carrying major advantages, molecular testing may also present some limitations, such as high cost, limited accessibility in many countries, and limited information using targeted approaches. Molecular testing has a different pattern of advantages and limitations than protein-based analyses. Therefore, the optimal use of molecular testing is frequently not as a standalone approach but in combination with protein-based techniques. The optimal combination depends on the resources available and the clinical challenge, to ultimately improve SCD care.

The laboratory diagnosis of antiphospholipid syndrome (APS) relies on detecting persistent antiphospholipid antibodies (aPL), including lupus anticoagulant (LA) as one of the three laboratory criteria. LA is a well-established risk factor in APS and the cornerstone of APS diagnosis, identifying triple-positive patients. LA testing is supported by testing guidelines, but challenges remain with LA measurement, which is complex and susceptible to numerous pitfalls and interferences. A nuanced understanding of the technical and interpretative aspects of LA testing is crucial for accurate diagnosis. Limited to specific patient populations, the timing of testing in relation to clinical events is essential to avoid false results, and only persistent LA positivity is considered diagnostic. Proper sample preparation, choice of assays, test procedure, cutoff values, and strategies to handle anticoagulant therapy interference pose significant challenges in LA testing. While advances in the harmonization of test procedures and testing guidelines have improved diagnostic reliability, the complex nature of LA demands careful consideration of methodological issues and potential interferences, underscoring the importance of expertise and interdisciplinary communication in achieving accurate results. Interpretative comments and close interaction between clinical pathologists and clinicians are mandatory for diagnosis and patient management. This paper will focus on the technical aspects of the laboratory method and the interpretation of LA results in the diagnosis of APS with attention to specific situations where LA testing is difficult.

Introduction: The prototypic anti-platelet factor 4 (PF4) disorder-heparin-induced thrombocytopenia and thrombosis (HITT)-features immunoglobulin G (IgG) class antibodies that activate platelets, monocytes, and neutrophils in a mainly heparin-dependent fashion via Fcγ receptor-dependent cellular activation. The identification in 2021 of an ultrarare HITT-mimicking disorder, vaccine-induced immune thrombocytopenia and thrombosis (VITT)-triggered by two different adenoviral vector vaccines-abruptly broadened the spectrum of recognized anti-PF4 disorders.

Objective: To classify platelet-activating anti-PF4 disorders, both HITT/HITT-like and VITT/VITT-like.

Methods: Literature was reviewed from the perspective of a researcher-clinician involved in identifying novel anti-PF4 disorders.

Results: Atypical presentations of HITT with proximate heparin triggers but which evince heparin-independent platelet-activating properties ("autoimmune HITT") have been recognized since 2001; heparin-independent platelet-activating properties also characterize HITT-mimicking disorders with undefined non-heparin triggers (e.g., post-knee replacement "spontaneous HITT"). Antibodies identical to those of (vaccine-induced) VITT can rarely be triggered by natural adenovirus infection. HITT and VITT antibodies recognize different epitopes on PF4. All the aforementioned anti-PF4 disorders are acute, transient, and self-limited. Recently, however, chronic anti-PF4 disorders featuring potent VITT-like properties of monoclonal proteins (M-proteins) have been identified: this oftentimes treatment-refractory entity, named "VITT-like monoclonal gammopathy of thrombotic significance" (VITT-like MGTS), dramatically expands the clinical spectrum of recognized anti-PF4 disorders. Anti-PF4 disorders with heparin-independent platelet-activating antibodies, whether HITT or VITT, may require management strategies beyond anticoagulation alone, including high-dose intravenous immunoglobulin (IVIG) or (for VITT-like MGTS) the Bruton's tyrosine kinase inhibitor, ibrutinib.

Conclusion: Clinicians and laboratorians require knowledge of the rapidly broadening spectrum of recognized acute and chronic anti-PF4 disorders.

Introduction: There are important challenges with the measurement and interpretation of direct oral anticoagulant (DOAC) anticoagulant effect including a lack of therapeutic ranges, inaccuracy of routinely available coagulation assays, lack of established thresholds for clinically significant effect, and uncertainty about how to apply the results to patient care.

Objective: In this narrative review, we provide a practical approach to DOAC measurement in clinical practice.

Methods: By summarizing the literature and using illustrative cases, we highlight key principles of commonly available tests, outline potential indications for measuring DOAC drug levels, and provide guidance on interpreting results to inform management decisions.

Conclusion: While DOACs do not require routine monitoring of anticoagulant effect, assessment of plasma DOAC concentration may be helpful in select emergency and non-emergency clinical scenarios.