Not Your Grandmother’s Hematology

Last month we celebrated Lab Week, to recognize and show appreciation for Medical Laboratory Scientists and Technicians. Lab week is also a time to reminisce, and tell stories of the lab “in the old days.” I have worked with many technologists who have now been in the field for more than 50 years, and some who have worked in the same hospital all that time! Lab techs love to share stories about their experiences over the years, the days without computers, old methodologies, ancient lab equipment and manual testing. Listening to these stories always makes me think about just how far we have come in the field in the last 50- 60 years, and gives me a true appreciation for modern technology. It causes me to reflect on all the changes and developments that enable us to give physicians a wealth of knowledge that was previously unavailable.

During the first half of the 20^th century, the complete blood count (CBC) was performed using exclusively manual techniques. Blood cell counts (erythrocytes, leukocytes, thrombocytes) were performed under the microscope using diluted blood samples and a hemocytometer. For each specimen, a technologist spent about 30 minutes at a microscope manually counting the cells and calculating the total count using a mathematical formula. A spectrophotometer was used to perform the hemoglobin by the cyanmethemoglobin method, and a spun hematocrit was performed. Indicies were calculated. A manual smear was made, stained, and cells were counted and differentiated under the microscope. To complete a CBC, all these procedures had to be performed individually, with duplicate testing and applying mathematical calculations, and could take over 2 hours. After all these tests were performed, results were reported on paper and sent to the patient’s doctor or the nursing floor.

In 1953 Wallace Coulter patented the Coulter Principle for counting and sizing microscopic particles. The Coulter Principle can be used for measuring any particles that can be suspended in an electrolyte solution, and has been used in the food and drug industry, in beer making, in the manufacture of construction materials and thousands of other applications. However, probably the most important application has been in the medical field where it has revolutionized the science of hematology. Coulter suspended red blood cells in a solution and, with an electrical current flowing, passed the solution through an aperture. As the cells pass through the current, the impedance between the terminals changes, and this change can be measured as a pulse. The first Coulter Counter measured the number of cells by counting the number of these pulses. The first Model A Coulter Counter was sold in 1956, manufactured in Coulter’s basement in Chicago. The Model A counted red blood cells in a sample in 10 minutes, a marked improvement over manual counting! The Coulter Counter was hailed for its speed, accuracy, and opportunities for reducing human error, tedium and eye strain.

During the 1960’s, an improved Model B Coulter Counter was developed and Model A and Model B were used to count both leukocytes and erythrocytes. Other Coulter Counter models soon followed, and competitors entered the market with their versions of cell counters. Within a decade, nearly every hospital in the United States had a Coulter Counter, and the new, advanced Coulter Model F was widely used. In 1968 the first fully automated hematology analyzer, The Coulter Counter Model S was introduced, and could perform a seven-parameter CBC. The Model S could perform not only WBC and RBC counts, but also reported Hemoglobin, Hematocrit, Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH) and Mean Corpuscular Hemoglobin Concentration (MCHC).  In 1955 it took one or several technologists 2 hours to perform a CBC, and in 1969 an automated hematology analyzer could analyze a sample in under 2 minutes.

Image 2. “Woman Using a Model F Coulter Counter Cell Counter,” 1969. Beckman Historical Collection, Box 58, Folder 94. Science History Institute. Philadelphia. https://digital.sciencehistory.org/works/736664585.

As these improvements and advancements continued, and Coulter patents expired, new manufacturers entered the field. Technicon Instruments Corporation, Ortho Diagnostics, Instrumentation Laboratories and Toa Medical Electronics, (presently Sysmex Corporation) were among the first Coulter competitors. From a simple automated blood cell count, to the first seven-parameter CBC, we saw hematology changing before our eyes. More reliable automated platelet counts were added in the 1970s. In the 1980s we saw the first hematology analyzers that could perform automated differentials and the first automated reticulocyte analyzers. In the late 1990’s, we saw the advent of digital cell images and automated manual differentials.

Today, modern automated cell counters sample blood, and quantify, classify, and describe cell populations. These instruments use optical light scatter, impedance methods based on the Coulter principle or a combination of both optical and impedance methods. Progressive improvement in these instruments has allowed the enumeration and evaluation of blood cells with great accuracy, precision, and speed, at a very low cost per test. The latest descendant of the Model A Coulter Counter, the LH 750, can determine 26 reportable hematological parameters. The Sysmex XN-9100 with four XN analyzers reports 30 parameters and has a throughput of up to 400 CBCs and 75 smears per hour. Today’s analyzers can accomplish more and more routine diagnostics, and the role of the hematology technologist continues to evolve and expand.

This is not your grandmother’s hematology! We’ve truly come a very long way in 60 years. Modern hematology instruments not only perform a CBC, but they give us next generation diagnostics as well. Many give us advanced clinical parameters and other new parameters which provide physicians with additional information about the state of blood cells. We can report out immature granulocytes with every differential, automated nucleated red blood cell counts, immature platelet fractions and fluorescent platelet counts, and report the amount of hemoglobin in reticulocytes and the immature reticulocyte fraction. Future directions of hematology instrumentation include the addition of even more new parameters. In upcoming Hematology blogs I will be presenting case studies that highlight each of these advanced clinical parameters and discuss how physicians can use this new information in making diagnoses.

References

1. Beckman Coulter, Inc. History http://www.fundinguniverse.com/company-histories/beckman-coulter-inc-history/
2. https://www.beckman.com/resources/discover/fundamentals/history-of-flow-cytometry/the-coulter-principle 
3. Clinics in laboratory Medicine. Development, history, and future of automated cell counters Green R, Wachsmann-Hogiu S. Clin Lab Med. 2015 Mar;35(1):1-10. doi: 10.1016/j.cll.2014.11.003. Epub 2015 Jan 5. March 25, Vol 35, Issue 1, p1-10
4. Cytometry: Journal of Quantitative Cell Science. Wallace H. Coulter: Decades of invention and discovery Paul Robinson First published: 17 April 2013 https://onlinelibrary.wiley.com/doi/epdf/10.1002/cyto.a.22296
5. J.clin.Path. An assessment of the Coulter counter model S P.H.Pinkerton,I.Spence, J.C. Ogilvie, W.A Ronald, Patricia Marchant, and P.K, Ray. 1970,23,68-76 http://jcp.bmj.com/content/jclinpath/23/1/68.full.pdf
6. SLAS TECHNOLOGY: Translating Life Sciences Innovation. The Coulter Principle: Foundation of an Industry. Marshall Don, Ph.D., Beckman Coulter, Inc.. Volume: 8 issue: 6, page(s): 72-81. Issue published: December 1, 2003 https://doi.org/10.1016/s1535-5535(03)00023-6
7. Medical Electronic Laboratory Equipment 1967-1968. G.W.A Dummer and J. MacKenzie Robertson. 1967 Pergamon Press

-Becky Socha, MS, MLS(ASCP)^CM BB ^CM graduated from Merrimack College in N. Andover, Massachusetts with a BS in Medical Technology and completed her MS in Clinical Laboratory Sciences at the University of Massachusetts, Lowell. She has worked as a Medical Technologist for over 30 years. She’s worked in all areas of the clinical laboratory, but has a special interest in Hematology and Blood Banking. When she’s not busy being a mad scientist, she can be found outside riding her bicycle.