TELE-HEMATOLOGY: CRITICAL DETERMINANTS FOR SUCCESSFUL IMPLEMENTATION

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1 Blood First Edition From Paper, prepublished by online guest on September July 4, , For 2003; personal DOI use /blood only. TELE-HEMATOLOGY: CRITICAL DETERMINANTS FOR SUCCESSFUL IMPLEMENTATION Short title: IMPLEMENTING TELE-HEMATOLOGY Urs Luethi¹, Lorenz Risch¹, Wolfgang Korte², Margrit Bader¹, Andreas R. Huber¹ From the ¹Department of Laboratory Medicine, Kantonsspital, Aarau, Switzerland and ²Institute for Clinical Chemistry and Hematology, Kantonsspital, St. Gallen, Switzerland Correspondence: Andreas R. Huber, MD Professor and Director Department of Laboratory Medicine Kantonsspital Aarau, 5001 Aarau, Switzerland Tel: ; Fax: andreas.huber@ksa.ch Abstract word count: 149 Text word count: 1194 Copyright (c) 2003 American Society of Hematology 1

2 Despite modern technologies such as immunophenotyping and molecular probing cytomorphological examination of stained peripheral blood smears by microscopy remains the mainstay of diagnosis in a large variety of diseases. This holds true especially in underdeveloped or rural areas where profound expertise and equipment is not easily available. Although communication technologies have been dramatically improved, telehematology has not become routine. To date, little information is available on which procedures are critical for successful implementation. Therefore, a study evaluating possible factors that prevented implementation of tele-hematology was initiated. We found that staining technique, smearing procedure, training skills, number of captured images and prevalent disease influenced the accuracy of diagnosis by the reference lab. Employing realtime teleconferencing allowed for overcoming these deficits. Together, when certain rules are observed, tele-hematology allows for rapid, accurate, standardized and cheap expert advise. This should improve treatment of patients in remote areas where expertise is not available. Introduction In clinical laboratory testing evaluation of peripheral blood and bone marrow smears is essential for diagnosis of diseases especially those of the blood. Although technically simple morphological analysis requires considerable skill. For accurate diagnosis of blood diseases, well trained and experienced medical laboratory technicians, as well as experienced hematologists are required. Technicians in small peripheral medical laboratories may be unexperienced in evaluating rare pathologies. Because early diagnosis in several hematological diseases is important (for example acute promyelocytic leukaemia associated frequently with disseminated intravascular coagulation), rapid available expert advice would represent a major step in quality improvement of peripheral health care. In remote areas, referral of the patient to tertiary care centers is only justified after a solid diagnosis is obtained. Because many disorders can be diagnosed by pathognomonic blood smears, dangerous delays and unnecessary referrals could be avoided if appropriate hematological expertise is obtained in time. But unlike numerical data such as complete blood count and biochemical markers, it has been difficult to report cell morphology from remote sites. Digital transmission in the field of the pathological testing is used in increasing frequency [1]. In hematology, support of diagnosis and clinical practices using digitally transmitted images is not yet routine. Recently, standardized systems for digital transmission of visual information in hematology (tele-hematology) have become available. It is now possible to handle images viewed through a microscope on a computer by electronically capturing pictures of peripheral blood and bone marrow smears using CCD cameras in a standardized fashion. Although the 2

3 technical aspects of rapid transmission of high quality images has been solved, specific hematological issues have not been addressed to date, such as the role of staining procedure, level of experience and training of staff obtaining images, and competence of staff hematologist evaluating the images. To establish the hematology specific requirements for correct diagnosis of a blood smear obtained at a remote site, patients with a variety of diseases were analyzed in a blinded fashion. This included 30 different cases with distinct diseases. This could prove useful in countries with large rural areas (China, Canada, Greece, etc.) or in emerging countries. Nevertheless, even in privileged countries with high population density, second opinion gathering through standardized tele-hematology might prove useful as well. Study design In an experimental setting employing a newly developed tele-hematology system (LAFIA, Sysmex, Japan), the situation between a small peripheral routine lab and a hematology reference lab was simulated. The transmitting workstation (peripheral lab) was located remotely from the receiving workstation (reference lab). The reference lab (featuring a technician with wide experience in hematology and a hematologist) was requested to evaluate the chosen photographs of blood smears received from the peripheral lab by (Fig. 1). The diagnosis were compared to direct microscopic evaluation of the smears by an expert (gold-standard) without the use of tele-hematology. Several factors influencing the quality of expert advice were examined. These included a staining or smear technique different from the reference lab, different numbers of transmitted photographs (1 or 3 per case), and different levels of expertise of the person in the peripheral lab selecting the photographs (hematologist, general practitioner and clinical chemistry technician). The impact of these factors on the accuracy of expert diagnosis was assessed by transmitting ( ) different sets of photographs (JPEG-Format) obtained from blood smears of 30 different cases covering a wide variety of common hematological diseases (Tab. 1). The impact of teleconferencing was evaluated employing real time transmission of the microscopic procedure. This is a dynamic system that transmits live images of smears from the microscope at the remote site to a monitor at the reference lab. It provides for the expert the possibility to control the microscopic procedure while viewing simultaneously, giving technical instructions in selecting diagnostic fields and adjusting focus magnification and illumination. The two participants can communicate by phone and draw each other s attention to specific details. Therefore, with real time hematology the smears can be analyzed as with locally available microscopy. Statistics were based on the Chi-square test (applying the Yates' correction for continuity) comparing the proportion of correctly reported 3

4 expert diagnosis to the gold-standard. P-values were calculated two-tailed, the level of significance was set at Results and discussion Images acquired by LAFIA currently provide a 640 by 480 pixel image resolution and were stored in JPEG format (approximately 250 kb). These electronic images imported into a computer by a CCD camera and sent by can reproduce microscopic findings very accurately. As expected, employing a hematologist in the peripheral laboratory, the diagnostic accuracy in the reference lab achieved 100% when transmitting 3 pictures per case. Interestingly, when the hematologist was mailing only 1 photograph per case, the diagnostic accuracy dropped to 57% (17/30; p<0.001). The difficulty was that a proper number of images of cells was not reached with only 1 photograph per case. The expert diagnosis was the better the more cells were available for evaluating. Even when a hematologist in the peripheral lab transmitted 3 pictures of smears prepared with a different stain (Pappenheim) than that used in the reference lab (Wright stain) the accuracy was lower (27/30; n.s., p=0.24). Also the use of a different smear technique (automation vs. spun smears) decreased the accuracy to 72 % (18/25; p=0.008). Disorders of red blood cells were judged accurately in most cases in almost all settings. Problems in judging the smears arose predominantly in disorders of white blood cells (e.g. lymphoproliferative disorders and acute leukaemia), especially when leukopenia was present in addition. Cell characteristics such as nuclear reticular structure, presence or absence of nucleolus, granular or color tone of cytoplasm often enabled the diagnosis. Further, a general practitioner transmitting 3 pictures allowed 63% (19/30; p=0.001) and the clinical chemistry technician transmitting 3 pictures only 37% diagnostic accuracy (11/30; p<0.001). Thus, a lower level of specialized knowledge of the person in the peripheral lab chosing the photographs resulted in a significantly lower accuracy of expert advice. The lower skilled persons often selected photographs that were not representative for the diagnosis, e.g. normal blood cells in stead of blast cells in case of acute leukaemia. This deficit was compensated if real time microscopy was available. This method enabled a clinical chemistry technician to obtain images that improved the accuracy significantly to 100% (p<0.001). Interpretation of images, sent by an inexperienced technician was more difficult as demonstrated. However, a basic knowledge in hematology at the periphery is sufficiant for sending the right images to the reference lab. No expert experience was necessary. Real time haematology would overcome these difficulties, yet would be an laborious and expensive alternative method. Standardisation of staining and smearing procedure, capturing of 3 images, and a minimum of training of a technologist is sufficient for successful telehematology together with a modest technical investment. 4

5 We conclude that transmitting blood smear photographs via is feasible to offer rapid expert advice to peripheral laboratories. However, there are factors negatively affecting the accuracy of tele-hematology diagnosis. Real time tele-hematology is the method of choice to overcome these factors. As an other option it facilitates a second opinion from a colleague, who has particular expertise in a special field, or to confirm the own diagnosis by asking the advice of an expert. 5

6 References: 1. Leong FJ. Practical applications of Internet resources for cost-effective telepathology practice. Pathology Nov;33(4):

7 Table 1: Selected cases. Case 01: Normal blood smear Case 16: AML M2 Case 02: Malaria Case 17: CML-BP Case 03: Sickle cell disease Case 18: May-Hegglin anomaly Case 04: Thalassaemia major Case 19: AML M4 Case 05: Spherocytosis Case 20: Hairy cell leukaemia Case 06: Hemolytic anaemia Case 21: AML M7 Case 07: HUS/TTP Case 22: Parasitaemia * Case 08: Megaloblastic anaemia Case 23: Cytomegaly Case 09: Microcytic anaemia Case 24: ALL Case 10: Ovalocytosis Case 25: AML M6 * Case 11: Howell-Jolly bodies * Case 26: Infection/Sepsis * Case 12: Pelger-Huet anomaly Case 27: Mononucleosis Case 13: Osteomyelofibrosis Case 28: AML M5a Case 14: CML-CP Case 29: Sézary syndrome * Case 15: Myelodysplastic syndrome Case 30: CLL *Not represented in the test setting panel employing a different smear technique. 7

8 Figure 1: Examples of blood smear photographs transmitted from the peripheral lab to the reference lab. Malaria (left) and acute leukaemia (right) are selected. 8

9 vs. Gold-Standard Diagnostic accuracy in reference lab % Hematologist, 3 pictures Different stain, Hematologist, 3 pictures Gold-Standard, direct microscopy Different smear, Hematologist, 3 pictures p=0.008 p<0.001 p=0.001 p<0.001 Hematologist, 1 picture General practitioner, 3 pictures Clinical chemistry lab technician, 3 pictures Real-time telemicroscopy, clin. chem. lab technician Figure 2: Settings in the peripheral lab influencing the diagnostic accuracy in the reference lab using tele-hematology. 9

10 Prepublished online September 11, 2003; doi: /blood Tele-hematology: critical determinants for successful implementation Urs Luethi, Lorenz Risch, Wolfgang Korte, Margrit Bader and Andreas R Huber Information about reproducing this article in parts or in its entirety may be found online at: Information about ordering reprints may be found online at: Information about subscriptions and ASH membership may be found online at: Advance online articles have been peer reviewed and accepted for publication but have not yet appeared in the paper journal (edited, typeset versions may be posted when available prior to final publication). Advance online articles are citable and establish publication priority; they are indexed by PubMed from initial publication. Citations to Advance online articles must include digital object identifier (DOIs) and date of initial publication. Blood (print ISSN , online ISSN ), is published weekly by the American Society of Hematology, 2021 L St, NW, Suite 900, Washington DC Copyright 2011 by The American Society of Hematology; all rights reserved.