CLINICS IN LABORATORY MEDICINE

Platelet Subpopulations: Characteristics, Function, Clinical Relevance, and Translational Potential
Song AB and Battinelli E
Beyond playing a role in primary hemostasis, platelets can be characterized by several subpopulations, each with distinct characteristics and contribution to human pathophysiology. Procoagulant platelets, related to aggregatory and apoptotic platelets, contribute to thrombin generation and are implicated in cardiovascular, inflammatory, and oncologic disease. Procoagulant platelets contribute to tumorigenesis, and tumor-educated platelets are promising biomarkers in cancer assessment. Reticulated platelets are associated with high platelet turnover states. Megakaryocyte subpopulations are also being characterized with regards to thrombopoietic, inflammatory, and immunomodulatory roles. This article summarizes the rich diversity seen across numerous platelet subpopulations.
Machine Learning and Artificial Intelligence-Based Clinical Decision Support for Modern Hematology
Zhang C, Lam BD, Lucas F and Foy BH
Hematology is one of the most data-rich areas of medicine and has consistently been at the forefront of technological innovation. With the increasing integration of machine learning (ML) into the diagnostic process, it is vital that both patient-facing and laboratory-facing members of the care team understand how these tools may interact with existing workflows and affect their work. We review the current landscape of ML research and clinical applications. We cover a wide variety of subdomains (eg, hematopathology, hemoglobinopathies, and coagulopathy) and explore both the success and limitations of corresponding research and deployments.
von Willebrand Disease and von Willebrand Factor: Laboratory Standards and Methods Regarding von Willebrand Factor Activity Assays, von Willebrand Factor Propeptide Assays, and Multimer Methodology
Hutchison B, Podd A and Haberichter SL
von Willebrand disease (VWD) is the most common hereditary bleeding disorder in humans, 11 caused by a qualitative or quantitative defect in von Willebrand factor (VWF). VWD is diagnosed via tests of VWF quantity and function. Herein, we describe the recommended algorithmic testing strategy for VWD diagnosis, describe and compare available assays for evaluating VWF function, and discuss the utility and difficulties of VWF multimer analysis.
High-throughput Sequencing in the Diagnosis of Inherited Bleeding and Clotting Disorders: Technical and Interpretive Considerations Necessary for Accurate Reporting and Clinical Application
Miller AP, Brett BT, Riley JD and Trapp-Stamborski V
Genetic testing is a valuable tool for diagnosing bleeding and clotting disorders. Guidelines exist to aid laboratories in performing genetic testing and interpreting results, but these are often broad and lack gene-specific or disease-specific recommendations. This article examines the current state of genetic testing for these conditions, highlighting key challenges including variant calling and bioinformatic pipelines, panel design with respect to patient phenotypes, and variant interpretation with evolving classification frameworks. By addressing these complexities, we aim to provide a clearer understanding of the technical and interpretive considerations necessary for accurate genetic reporting and meaningful clinical application.
Novel Clinical and Laboratory Correlations for Antiphospholipid Syndrome
Llorente-Chávez A, Burgos-Canales S, Beverido-Florido ÁM and Orozco-Collazo A
The diagnosis of antiphospholipid syndrome remains a challenge. The 2023 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria improve sensitivity and specificity; it does not, however, surpass clinical judgment. The titers and positivity of antiphospholipid antibodies may change over time, depending on the clinical manifestation and during the acute event. Multiple studies have identified novel laboratory correlations that are associated with different clinical manifestations, risk of complications, and as potential biomarkers in the follow-up of the disease. This review explores the different assays that could be useful for the diagnosis and prognosis of this disease.
Disseminated Intravascular Coagulation and Advances in D-Dimer Testing: Progress in Harmonization of Clinical Assays and Innovative Detection Methods
Scarlatescu E, Maier CL, Levy JH and Iba T
The measurement of D-dimer, a fibrin degradation product, has become integral to diagnosing and managing thrombotic disorders, particularly disseminated intravascular coagulation. This report synthesizes current knowledge on D-dimer biochemistry, assay methodologies, clinical utility, and ongoing challenges in standardization. By analyzing recent advancements in harmonization efforts and innovative detection technologies, this review highlights the critical role of D-dimer in coagulation diagnostics while addressing persistent limitations in specificity and assay variability. Emerging techniques, such as mass-spectrometry and aptamer-based sensors, demonstrate promise for overcoming current barriers, though widespread clinical adoption requires further validation.
Hemostatic Disorders Following Severe Acute Respiratory Syndrome Coronavirus 2 Infection, COVID-19 Vaccination, and Long-COVID Syndrome: Current Evidence and Controversies in Clinical Practice
Vishnu P and Aboulafia DM
The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented profound global health challenges. Beyond acute illness, a substantial proportion of individuals experience persistent symptoms including fatigue, brain fog, and post-exertional malaise, collectively known as Long-COVID. Among the complications associated with SARS-CoV-2 infection and vaccination, hemostatic disorders ranging from mild platelet dysfunction to severe thromboembolic events, and rare but serious coagulation-related adverse effects, such as vaccine-induced immune thrombotic thrombocytopenia, have emerged as a significant concern. Herein we provide an overview of current information and controversies surrounding hemostatic complications in SARS-CoV-2 infection and COVID-19 vaccination.
Recent Advances in Extended Half-Life Products, Nonfactor Replacement Therapies, and Gene Therpy for the Treatment of Hemophilia
Vishnu P and Aboulafia DM
Hemophilia, a rare X-linked hereditary bleeding disorder, is characterized by deficiency of coagulation factors. Symptoms range from spontaneous joint and muscle bleeds to life-threatening hemorrhage, for which patients require frequent infusion of coagulation factors, profoundly impacting their quality of life. Novel therapeutics and advances in gene therapy now offer patients long-term disease control and improved quality of life. Here, we focus on important developments in the use of extended half-life factor products, non-factor replacement therapies, and gene therapy. We also highlight the mechanism of action, clinical efficacy, and safety of these newer approaches.
Women's and Transgender Issues in Thrombosis and Hemostasis: Laboratory Parameters of Coagulation and Fibrinolysis Influenced by Hormones, Including Pregnancy and Postpartum
Abdulrehman J, Weyand AC and Shehata N
Exogenous estrogen, commonly in the form of combined hormonal contraceptives and menopausal hormone therapies, is associated with changes in coagulation proteins leading to increased risk of venous thromboembolism (VTE). Similarly, this prothrombotic milieu is recreated in pregnancy due to elevations of endogenous estrogen and progesterone. Endogenous elevations of these hormones decrease in the postpartum setting. Exogenous estrogen is also used as gender-affirming hormonal therapy with transgender women, but data on its thrombotic risk in this demographic are limited.
Implementation of Viscoelastic Testing at the Point of Care: Practical Pearls for Clinical Integration
Hermelin D
This article provides a comprehensive review of viscoelastic hemostatic assays, also known as viscoelastic testing, highlighting their transformative impact on bleeding and coagulation management across acute clinical care settings. Key sections discuss the latest Food and Drug Administration-approved devices, off-label pediatric and neonatal applications, and practical guidance for clinical implementation-including equipment placement, validation, training, and regulatory compliance. The article serves as both a comprehensive review and a practical implementation guide for clinicians, laboratorians, and administrators seeking to optimize patient outcomes through advanced hemostasis management with practical guidance for implementation, validation, and workflow integration.
Flow Cytometry Assessment of Platelet Phenotype, Function, and Cellular Interactions: Guidelines for Optimization and Assay Performance
Linden MD
Flow cytometry is an essential laboratory tool for assessing platelet phenotype, function, and cellular interactions. Applications include diagnosing specific platelet disorders (eg, Glanzmann thrombasthenia, Bernard-Soulier syndrome) and thrombocytopenias, monitoring antiplatelet therapy, and various research applications. Key performance considerations involve managing preanalytical variables, careful sample preparation (eg, buffers, stimulation, staining, fixation), comprehensive assay controls, and optimized instrument calibration and data acquisition (eg, trigger, flow rate, scatter transformation). Recent advances in multiparametric and imaging flow cytometry enable identification of distinct platelet subsets.
Connecting Clinical Practice and the Hematology Laboratory
Lucas F and Sabath DE
Leadership's Role in Paving the Path to Diversity, Equity, and Inclusion in Laboratory Medicine
Lucas F, Soles R, Upton MP and Jackson NR
Leadership is critical in promoting diversity, equity, and inclusion (DEI) in laboratory medicine and pathology. Leaders must foster environments that embrace diverse perspectives, fair treatment, and inclusion. By highlighting emotional intelligence, trauma-informed leadership, and DEI principles, this article advocates for leadership that adapts to the needs of diverse teams and that fosters their empowerment in providing patient-centered care. This article also discusses how DEI-informed leadership can address gaps in formal leadership training and contributes to improved health care outcomes, staff retention, and the development of future leaders at all levels.
Promoting Gender Equality in Pathology and Laboratory Medicine Leadership
Nabulsi R and Mok D
The medical laboratory should promote gender equality and women's empowerment on a continual basis to ensure laboratory personnel are treated with respect and equality at all times. Laboratory management should continue to work with human resource management personnel to implement reasonable policies, processes, and practices to address potential gender equality issues. The mechanism of addressing gender equality in the medical laboratory remains relatively unexplored; however, International Standard ISO 53800:2024 offers a practical framework for laboratory management to implement. In sum, effective equitable leadership will result in improved decision-making and ultimately boosting their profitability for relevant interested parties.
Leadership Approaches for Work-Life Balance, Well-Being, and Diversity, Equity, and Inclusion Support in the Laboratory
Abdelmonem M and Upton MP
In high-stress laboratory environments, effective leadership is essential to cultivating work-life balance, employee well-being, and diversity, equity, and inclusion (DEI). This article investigates 3 leadership styles: transformational, servant, and inclusive leaders and their roles in promoting work-life balance, well-being, and DEI in laboratory settings. The article also explores DEI initiatives as a critical leadership responsibility, recognizing that inclusive environments empower employees to perform optimally and contribute unique perspectives. This article emphasizes the importance of adaptable, empathetic, and inclusive leadership strategies to ensure productivity, satisfaction, and resilience in modern laboratories, especially as the industry faces complex technologic advancements and workforce demands.
The Impact of Inclusive Excellence Initiatives on Laboratory Wellness
Ware AD
In recent years, there has been increasing emphasis on the importance of diversity, equity, and inclusion (DEI) and well-being in the medical field. Interventions such as increasing early exposure to pathology, postsophomore pathology fellowship programs, clinical rotations through pathology services and laboratories, and increasing the visibility of diverse leadership have all shown to increase recruitment into the pathology workforce. Dedicated well-being initiatives that focus on both individualized and system-based interventions have been shown to have an impact on mitigating work-related stress. A unified approach to DEI and well-being has the potential to reinvigorate the pathology workforce and improve overall job satisfaction.
Addressing Burnout and Supporting Mental Health in Laboratory Medicine
Kawam A
Burnout is an occupational phenomenon that has been shown to affect the mental health of laboratory staff. This has major impacts on the daily functions of the laboratory which in turn affects the functions of the health care system at large. Interventions to mitigate the effects of burnout should prioritize systemic changes. Individual interventions although helpful, generally do not address the root causes of burnout. From an organizational standpoint, addressing burnout is crucial, as burnout is associated with increased costs, decreased employee engagement, and decreased patient satisfaction.
Pathology Clinics Can Address Pathology Burnout
Joseph L
Pathology clinic is a unique concept that has the potential to allay burnout and build resilience among pathologists. This article explores strategies and outcomes of such a concept in a community hospital setting in Lowell, MA.
Leadership Development for Pathology and Laboratory Medicine Residents and Fellows
Mirza KM and Kanakis CE
In the evolving landscape of health care, the role of pathologists and medical laboratory professionals extends beyond laboratory diagnostic expertise to encompass leadership within multidisciplinary teams. Despite this, formal leadership training-both in aspects within and outside our professional specialty-is often underrepresented in both pathology residency and fellowship programs. This article explores the imperative for intentional leadership development in pathology and laboratory medicine training, examines existing challenges, and proposes strategies to integrate leadership competencies into educational curricula for aspiring pathologist-leaders.
System-Wide Leadership
Sesok-Pizzini D and Pizzini MA
The article explores system-wide leadership, emphasizing the transition from functional to C-suite roles. Effective leadership requires fostering positive environments, leveraging emotional intelligence, and aligning organizational goals with a purpose-driven culture. Key areas of focus include adapting communication styles to build trust, embracing risk and failure to drive innovation, and fostering psychological safety to enhance team performance. The article highlights the importance of building diverse, high-performing teams and leveraging tools like artificial intelligence for decision-making. By prioritizing inclusivity, emotional intelligence, and resilience, leaders can create cohesive organizations that thrive in dynamic and complex environments.
Evolving Leadership in Laboratory Medicine
Mulder L