Introduction

The peripheral blood smear test (PBS) is one of the most essential diagnostic tools in hematology. Following a complete blood count (CBC), microscopic examination of a blood film, is the second most performed test in the hematology laboratory.1  A properly prepared and stained blood film, reviewed by skilled laboratory professionals, can reveal critical diagnostic insights that aid in clinical decision-making and patient management. Laboratories must establish standardized PBS procedures and clear criteria for identifying blood films that require further review, ensuring that significant findings are communicated promptly to the patient’s physician.1  

Peripheral Blood Smear Test Procedure

The peripheral blood smear (PBS) review is the cornerstone of hematology diagnostics, allowing for detailed analysis of blood cell morphology and composition. This review involves both absolute and relative quantification of different blood cell types, along with a detailed morphologic assessment of individual cells, thereby offering valuable insights into a wide range of hematologic disorders.

The blood smear primarily consists of three cell types: red blood cells (RBCs) the most abundant, white blood cells (WBCs), and platelets. 2, 3, 4  

The procedure of a PBS review involves the qualified laboratory professional evaluating RBC size, shape, and color, classification of WBC and platelet clump detection.. For example, any deviation in RBC indices, such as size, volume, or shape, may indicate an underlying conditions 2  such as intracellular parasitic infections, hemolytic anemias, thrombotic microangiopathies (TMA), and acute leukemias. 4   PBS reviews play a pivotal role in diagnosing a range of benign and malignant hematologic disorders. PBS morphological assessment, when integrated with CBC results and other laboratory data, can provide a definitive diagnosis or guide further diagnostic work-up and results in a cost-effective and efficient diagnostic tool.5  

Interpretation and Clinical Applications

Accurate interpretation of a PBS requires specialized visuospatial training and experience. 4   Experts utilize light microscopy for manual review or digital full field imaging which is preferred over isolated high-power field images, to ensure an accurate and complete assessment. 4  

Peripheral blood smear reports help to correlate findings within the patient’s clinical history, serving as a crucial resource for both clinicians and laboratory professionals. These reports facilitate diagnosis and recommend further diagnostic workup when necessary.5   Laboratory staff may also request PBS reviews as part of good laboratory practices or to comply with regulatory and accreditation requirements. In many laboratories, significant findings undergo evaluation by a qualified hemato-morphologist. 5  

These assessments guide further diagnostic investigations and confirm conditions.  While manual review remains an essential component, modern hematology laboratories are increasingly integrating automation and digital imaging technologies to enhance efficiency, reproducibility, and diagnostic accuracy.3  

Challenges in Manual Peripheral Blood Smear Review

Despite its diagnostic value, manual PBS review presents several limitations: 2, 4, 6  

• Labor-Intensive and Time-Consuming: Manual review requires skilled personnel and considerable time investment as analysis can be tedious and slow. In addition, there are challenges in experienced clinical laboratory staffing and medical technologist workforce shortages with a limited number of laboratory training programs. 7  
• Inter Observer Variability: Different technicians may interpret the same slide’s cell morphology differently, leading to inconsistent results.
• Lack of Standardization: Training and competence levels in laboratory personnel vary across laboratories, affecting reliability.   

A survey of 169 laboratories conducted by the IQMH Morphology Proficiency Testing program highlighted inconsistencies in PBS review procedures and practices. 1  

• Despite the availability of hematology analyzers, 86% of laboratories still relied solely on manual review, despite the availability of hematology analyzers.
• Only 2% employed dedicated morphology technologists. 
• 70% of laboratories did not mandate senior technologists to verify findings before physician review
•  30% lacked 24/7 access to a physician for morphological assessment. 

These limitations underscore the need for automation and digital solutions. full

Advances in Digitization for Peripheral Blood Smear Analysis

Technological advancements are addressing the inefficiencies of manual PBS analysis. Automation of PBS analysis has emerged as a key area of research and development. Digital imaging technologies, artificial intelligence (AI) and deep learning systems are reshaping the way hematologists assess blood smears, improving diagnostic precision and optimizing laboratory workflows.

The Role of Digital Assessment in PBS Analysis

Digital assessment technologies streamline the PBS review process by:

• • Triaging abnormal samples: Flagging abnormal samples for manual review reduces manual workload and turnaround times, and optimizes resources. 
  • Enhancing accuracy: Digital systems analyze a significantly larger number of cells and slide regions compared to manual methods, improving the characterization of cell parameters.
  • Reducing subjectivity: AI-driven solutions ensure consistent interpretations, minimizing human error and inter observer variability. 6  

• Improving the detection of rare or subtle morphological abnormalities: Deep learning applications in PBS analysis have further improved the detection and classification of hematologic disorders, outperforming traditional machine learning (ML) methods. These AI-powered digital systems can identify subtle morphologic changes in peripheral blood cells that may be overlooked during manual evaluation, facilitating earlier and more precise diagnoses. 3  

Scopio Labs’ Full-Field Digital Cell Morphology imaging platform,

One of the most significant advancements in digital PBS analysis is the Scopio Labs * Full Field digital morphology platform and its advanced Peripheral Blood Application application , which enhances hematology diagnostics with its high-resolution full field digital imaging capabilities. The novel Full-Field Morphology (FFM) technology developed by Scopio Labs supports the user in performing peripheral blood smear (PBS) analysis on a large scale of up to 1000 fields of 100x view in a routine manner, allowing a precise and highly sensitive classification and assessment of cellular and sub-cellular morphological parameters. 7   Unlike traditional digital imaging systems that provide only thumbnail images of individual cells, Scopio’s Full-Field digital microscopy solution scans and analyzes clinically relevant areas of  blood smears at high resolution, offering a comprehensive view for expert review. 3 Scopio’s Full-Field Peripheral Blood Smear™ application is the first solution which truly eliminates the need for manual microscopic examination.

The Scopio Labs Full Field Digital Morphology imaging platform utilizes AI-driven decision support to pre-classify WBCs into multiple subtypes, including neutrophils, eosinophils, basophils, lymphocytes, monocytes, immature myeloid cells, and blast cells. It also identifies nucleated RBCs, smudge cells, and artifacts with high precision. Platelet estimation is automated by locating and counting platelets across multiple fields of view, enhancing thrombocyte assessments. 3  

Another key advantage of Scopio Labs Full Field Digital Morphology Imaging Platform  is its ability to facilitate remote consultation and expert collaboration, allowing hematologists and laboratory professionals to review smears through a secure hospital network. This capability improves diagnostic turnaround time and ensures expert evaluation of complex cases without delays. 3  

As Scopio Labs Full Field Digital Morphology Imaging Platform continues to be integrated into routine laboratory workflows, it is expected to significantly enhance diagnostic performance, by improving efficiency, accuracy, and consistency while reducing the workload on laboratory personnel. 3  

The Future of Digital Automation in Hematology Laboratories

The peripheral blood smear test remains a cornerstone of hematologic diagnosis, offering critical insights into various blood disorders. While manual microscopy continues to play an important role, the integration of digital imaging and AI-driven classification is revolutionizing PBS analysis. These technological advancements enhance efficiency, improve diagnostic consistency, and ensure better patient outcomes. Over the next decade, the widespread adoption of full-field digital microscopy and AI-driven blood smear analysis will transform hematology workflows, enabling faster, more reliable, and highly scalable diagnostic capabilities to support improved patient care. 3 However, challenges still remain in truly and comprehensively automating the entire process and enabling  precise and highly sensitive automated quantification of cellular and sub-cellular morphological parameters. As laboratories embrace automation, the future of hematology PBS and morphology diagnostics is poised for greater accuracy and innovation.On the horizon is a move from pure morphological analysis to a digital morphometric PBS approach for challenging diagnostic conditions such as MDS (Myleodysplastic Syndrome), 8 as well as for monitoring treatment response in patients undergoing Chimeric Antigen Receptor T-cell therapy for haematological cancers such as relapsed/refractory diffuse large B-cell lymphoma (DLBCL). This ushers in a new era of possibility from morphological form and structure to precise characterization of activated morphology of CAR T transduced cells and their correlation with response to treatment through digital full field PBS analysis rather than more expensive flow cytometry and PCR. 9 

References:

1. Leung E, Johnston A, Olsen B, Chang H, Martin T, Wozniak M, Good D. Laboratory practices for manual blood film review: Results of an IQMH patterns of practice survey. Int J Lab Hematol. 2021;43(2):184-190. doi: 10.1111/ijlh.13343
2. Navya KT, Prasad K, Singh BMK. Analysis of red blood cells from peripheral blood smear images for anemia detection: a methodological review. Med Biol Eng Comput. 2022;60(9):2445-2462. doi: 10.1007/s11517-022-02614-z
3. Lewis JE, Pozdnyakova O. Digital assessment of peripheral blood and bone marrow aspirate smears. Int J Lab Hematol. 2023;45 Suppl 2:50-58. doi: 10.1111/ijlh.14082
4. Chase ML, Drews R, Zumberg MS, Ellis LR, Reid EG, Gerds AT, et al. Consensus recommendations on peripheral blood smear review: defining curricular standards and fellow competency. Blood Adv. 2023;7(13):3244-3252. doi: 10.1182/bloodadvances.2023009843
5. Gulati G, Song J, Florea AD, Gong J. Purpose and criteria for blood smear scan, blood smear examination, and blood smear review. Ann Lab Med. 2013;33(1):1-7. doi: 10.3343/alm.2013.33.1.1.
6. Mohammed EA, Mohamed MM, Far BH, Naugler C. Peripheral blood smear image analysis: A comprehensive review. J Pathol Inform. 2014;5(1):9. doi: 10.4103/2153-3539.129442.
7. Leber AL, Peterson E, Bard JD. The Hidden Crisis in the Times of COVID-19: Critical Shortages of Medical Laboratory Professionals in Clinical Microbiology.J Clin Microbiol 2022;60(8): e0024122.doi: 10.1128/jcm.00241-22.
8. https://scopiolabs.com/clinical-impact/automated-digital-morphometry-of-peripheral-blood-smears-detects-both-infrequent-events-and-cellular-population-patterns-in-myelodysplastic-syndrome/
9. Fridberg G, Horn G,  Globerson Levin A, Benisty, D, Kay, S, Glait-Santar C, et al. The Clinical Significance of Circulating Lymphocytes Morphology in Diffuse Large B-Cell Lymphoma As Determined by a Novel, Highly Sensitive Microscopy. Cancers 2023(15): 5611. https://doi.org/10.3390/cancers15235611

Disclaimer:

Scopio Labs’ Full-Field Peripheral Blood Smear application is CE marked and FDA-cleared, and its commercially available across the U.S., UK and Europe and other territories.

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