Transfusion Medicine Case Study: Positive Pretransfusion Test

A 72 year old man was admitted to the hospital for an aneurysm repair. The physician ordered a type and crossmatch for 6 units of blood in preparation for surgery. The patient history included surgery in 2016 during which he was transfused with 4 units of RBCs.

patient’s blood type: A positive

antibody screen: negative

history: anti Jkb  (2016)

6 Jkb negative units were found and full crossmatches were performed. One of the 6 donor units was incompatible. What is the most probable explanation for these findings?

If the patient has a negative antibody screen, and no history of an antibody, most facilities would do an electronic crossmatch or an immediate spin crossmatch. The immediate spin (abbreviated) crossmatch will simply verify ABO compatibility. However, if the patient has a positive antibody screen, we must identify the antibody, phenotype the patient, and do a full AHG crossmatch with donor units that are antigen negative for the corresponding antibody. In this case, the patient had a history of an antibody, so the antibody must be honored, and antigen negative units must be chosen for transfusion.

Kidd antibodies demonstrate dosage, are often weak, and can be found in combination with other antibodies. Because if this, they can be notoriously difficult to detect. They are usually IgG and are made in response to transfusion or pregnancy. Jkb has an antigen frequency of about 73% in the white population and about 43% in the black population. To find antigen negative blood, we consider that about 27% of units would be antigen negative. The tech working on the sample screened 21 units and found 6 that were Jkb negative.

AHG crossmatch results:

unit 1: compatible

unit 2: compatible

unit 3: compatible

unit 4: 3+ at AHG

unit 5: compatible

unit 6: compatible

There are 2 possible scenarios for the above results. A crossmatch is a test between donor’s red blood cells and patient’s plasma. Antigens, we know, are on red blood cells and antibodies are detected in the plasma. So, with a negative antibody screen, crossmatch incompatibility is due either to a patient antibody to a low incidence antigen on the donor red blood cells, or a donor cells with a positive direct antiglobulin test. We can easily rule in or out a positive donor DAT by performing a DAT on the segment. If the donor unit has a positive DAT, the unit should be quarantined and the positive DAT reported to the collecting facility. If the donor unit has a negative DAT, the patient likely has an antibody to a low incidence antigen.

Low frequency antigens are uncommon, but antibodies that recognize them are less rare. Fortunately, for patients with these antibodies to low frequency antigens, finding antigen negative compatible blood is easy. As we can see, 5 of the 6 chosen units were negative for the unknown low frequency antigen and were antiglobulin crossmatch compatible. The low prevalence of the antigen makes compatible blood readily available. If transfusion is necessary, it should not be delayed while waiting for identification of the antibody.

In this case, the antibody screen was repeated and the negative result was verified. In many cases, it may not be possible for a lab to identify the antibody because the lab may not have the necessary panel cells or typing reagents. Yet, these antibodies to low incidence antigens that react at AHG can be clinically significant and cause severe hemolytic transfusion reactions. To identify the antibody, you may need to send the sample to a reference lab for testing against a panel of reagent red cells that express low incidence antigens. Alternately, the donor red cells that were incompatible can be tested against known antibodies to low prevalence antigens  to help identify the antibody.

In this patient, anti-Wra was identified. The incompatible donor unit was verified to be Wra positive. Wra is part of the Diego system, usually IgG, and has ben implicated in hemolytic transfusion reactions.

One of the reasons I have written up this case is questions my Transfusion Medicine students often ask about exam and exam prep questions concerning incompatibility. Below are 2 questions to give examples of the confusion.

“At the indirect antiglobulin phase of testing, there is no agglutination between patient serum and screening cells. One of 3 donor units was incompatible.. The most probable explanation for these findings is that the:

  1. patient has an antibody directed against a high incidence antigen
  2. patient has an antibody directed against a low incidence antigen
  3. donor has an antibody directed against donor cells
  4. donor has a positive antibody screen”5

answer: b

“Which of the following would most likely be responsible for an incompatible antiglobulin crossmatch?

  1. recipient’s red cells possess a low incidence antigen
  2. anti-K antibody in donor serum
  3. recipient’s red cells are polyagglutinable
  4. donor red cells have a positive direct antiglobulin test”4

answer: d

I am asked why is one answer “low prevalence antigen” and one answer “positive DAT”? I typically ask questions of my students to let them reason out the answer. Take a careful look at the words antigen and antibody. Remember that a DAT is a test of red cells, the IAT tests for antibodies in plasma. A crossmatch uses donor red cells against patient plasma. Therefore, even though these are both reasons for the incompatibility of one out of multiple units, each question only has one answer of a common reason for such incompatibility. Be sure to read questions and use your theory and knowledge of testing when encountering discrepancies and problems in Blood Bank. To all of my students: Happy Studying for your ASCP exam!

References

  1. Fung, Mark K., Technical Manual 18th ed, Bethesda: AABB, 2014.
  2. Harmening, Denise M. Modern Blood Banking and Transfusion Practices, 7th edition, 2019.
  3. Schonewille, Henk, et al. “The importance of antibodies against low‐incidence RBC antigens in complete and abbreviated cross‐matching”. The Journal of AABB. 20 June 2003.
  4. BOC Study Guide, 5th edition. Clinical Laboratory Certification Examinations.  ASCP, 2016
  5. BOC Study Guide, 6th edition. Clinical Laboratory Certification Examinations.  ASCP, 2018

-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.

2020 Vision

Welcome back everybody! Thank you for all the engagement on my last post, Up In Smoke¸ where I discussed the plenary publications surrounding the vaping crisis and EVALI as new pulmonary pathology entity. This month, let’s start 2020 off right. After the holiday break and going on some of my last pathology residency interviews, I’d like to reflect on this new year by taking a look at 20 exciting things on the horizon for those of us in pathology and laboratory medicine!

So, let’s take a look at 2020 with some 20/20 vision… (sorry, not sorry)

20. Big, big, big, big data

Image 1. Can’t mention databases without this invaluable website that has made me look somewhat semi-competent in many instances! Thanks Pathology Outlines (Source: um, pathologyoutlines.com)

Last year, Elsevier’s Clinical Solutions Director in China discussed three topics that would impact our profession in 2019—so let’s start there. These first three go hand-in-hand in prepping the stage for 2020. Up first: the never-ending explosion of biomedical information and the continuing tidal wave of health data we don’t even know what to do with just yet! It’s a very interesting estimate that, by 2020 (aka now!) the whole sum of medical knowledge will double every 73 days. How on earth are we to manage, when compared to 1950 it would have taken 50 years to double? Well, the argument in the linked Elsevier blogpost discusses how evidence-based inquiry databases will store and organize this knowledge for us: think UpToDate, or ExpertPath, or ImmunoQuery…some of you are nodding your heads in relief, great, I’ll move on.

19. Precision Medicine

Image 2. PD-L1, or programmed death ligand 1, is one of several new targets for cancer therapy that utilized cellular checkpoints in cell cycles alongside T cell and NK cell functional immunity to fight cancer a little more precisely than classic chemotherapy regimens. Look at you, all up to date, and stuff. (Source: AstraZeneca graphic, azimmuno-oncology.com, content)

The second topic last year’s Elsevier’s blogpost discussed was the growth and rapid development of highly specific, targeted, individualized treatment plans. The mainstay example is of course how oncology treatments are moving away from one-size-fits-all chemotherapies to individualized mutation-specific immunomodulating therapy. (We’re moving like melting glaciers but moving nonetheless.) I was definitely well equipped with my ASCP online CE credits as I found myself discussing testing patients during my heme/onc training for PDL-1 and other tailored targets. We’re just starting to ride this wave and it’s definitely growing fast.

18. AI in healthcare (part 1)

Image 3. Artificial Intelligence is getting really good at pattern recognition. Why did I choose this picture? Oh, because it’s a study of how China-based JF Healthcare, a Siemens off shoot start up AI group, designed an algorithm that beat radiologist at Stanford on precision, delivery, and accuracy. Woah. (Source: hitconsultant.net)

Yep. I went there—it’s exciting! But notice I’ll come around after some other topics to really get into the heart of AI in path. Basically, the last point in the blogpost discussed the way smart software has been growing in medicine; particularly with radiology and surgery, using advancements in robotics and detection software to predict and stratify clinical information for patient care. Within this context let me quote them directly for you, “…there remains some uncertainty around the role of AI and its true impact on pathology, it is important to recognize that AI-based technologies or machines will never replace pathologists. Instead, such innovations will play an assistive role, augmenting the decision-making capabilities of pathologists and helping them perform better and faster…” All my pathologist friends may now exhale. It’s going to be okay. We’ll talk more about this at #10.

17. New Tech, New Toys

Image 4. You don’t have to go far to read about new tools and new tech. How’s this: a saliva-based rapid Malaria detection assay, courtesy of our friends at ThePathologist.com. New, rapid, accurate and deliverable diagnostics…now within spitting distance. Nailed it.

Pathologists are like the 007’s of the clinical team…at least when it comes to developing tech. There are so many new gadgets and tools we clinicians have available to us today. I delivered a recent TEDx talk where I discussed the “unrecognizable future” of medicine—and obviously now look for new and exciting ways to tell people I gave a TEDx talk. The important thing is that 73 days of doubling medical knowledge is happening so fast we don’t even know what we have available to us! Finger-print drug tests, smartphone facial capillary blood pressures, liquid biopsies, virtual MS-based immunohistochemical stains that never actually stain a single cell, cytology AI, deep data mining of free text pathology reports…it’s not a short list. It’s exciting, and we should all be sharing and collaborating to use these exciting tools together in creative ways for positive outcomes!

16. No More Silos

Image 5. Business and management have long discussed the importance of tearing down silos of knowledge in order to improve workflow and outcomes. It’s a growing conversation in healthcare and we’ve got our own isolated pockets of data that need to come out to the forefront, too. (Source: ERP Consulting, Estes Group Image, estesgrp.com)

Last year, I wrote a few pieces here on Lablogatory that mentioned High-Reliability Organizations (HROs) which require absolutely full sharing of responsibility as well as knowledge in order to solve problems and improve patient-care outcomes. There are many ways siloed thinking can harm the progress of any institution. It takes leadership, creative problem-solving, transparency, and teamwork. In the coming months of 2020, keep an eye out for pockets within your organizational environment that act as black holes or veils to keep pieces of critical data from the rest of the team. Encourage discussions between you and your peers, check biases about what you think might be important for one team vs. another, and try to share successes and failures as a group.

15. New Types of Colleagues

Image 6. We’re all different. And that’s ok. Each one of us is a brain, and an athlete, and a basket-case, a princess, and a criminal. Okay maybe not the last one, but we can all contribute in some important meaningful way. (Source: The Breakfast Club, 1985)

What I just mentioned about engaging in new conversations with folks you might not have worked with before—its not groundbreaking, its just good practice! In order to tear down #16’s silos, we’ve got to seek out and explore new ways to collaborate with colleagues outside our everyday scope. There will always be discussions about generational divides and differences that create culture strife in the workplace, or political/opinionated schisms that divide even the most cohesive of medical specialties. (I’m looking at you ACOG, ACP, ASCCP, and others: it’s Cervical Cancer Awareness Month, can we just agree on some guidelines already…) Soapbox over. But seriously, this isn’t a new concept. Feel like a lab half filled with boomers and millennials can’t make the cut? Well, the Harvard Business Review gave us great recommendations for this exact type of interpersonal growth exercise—in the NINETIES! The take home message: having an open culture and proactive leadership allows for fruitful exchange and growth!

14. Digital Pathology!

Image 7. Bigger, I want these screens bigger! The desk of tomorrow’s anatomic pathologist might have less glass and more pixels, screens, and queued data with high-output servers that are stocked with smart software to sift out normal results so they can focus on really tough morphologies. Maybe even with augmented reality software, or other crazy stuff I can’t think of yet! (Source: Inspirata, digital pathology)

It’s coming. You can’t stop it. It’s exciting. I don’t care what you think. Well I actually do care, but don’t knock digi-path till it grows into whatever it’s going to become. The desk of the (anatomic) pathologist-of-the-future will look a lot different from today and that’s really cool. Once upon a time, a very long, long time ago—in the eighties maybe—radiologists still had films where we actually used radiation to change the exposure of images to be read over a light box. Classic scene, right? Doctor, the x-ray is ready! *THWIP* *CLICK* *BUZZ* and cue the contemplative stare on the wall light. Then, they went digital and get to hang out in the dark with four computer screens and coffee, and really comfy chairs. I mean what a form of progress, can’t deny.

13. MS Methodologies

Image 8. Okay, MSI crash-course time. All you really need to know is that this method allows for great specimen preservation on tiny samples, high resolution, the ability to combine with molecular testing, and fascinating implications for margin detection, mutation analyses, and more! (Source: https://blog.waters.com/molecular-visualization-ms-imaging-delivers-insights-for-cancer-research)

In my mailbox this month, is another excellent edition of The Pathologist and in it there’s a great article on Mass Spec imaging transitioning from a research tool to a clinical one. Woah. We’ve all talked about and praised MALDI-Tof methods for microbiologic assays and detection, but the expanse of mass spectrometry has developed rather quickly. Now, it’s looking for a niche in routine laboratory diagnostics outside of the old chemistry analyzer… It’s a new, non-destructive way of examining tissue and gleaning data from the smallest pieces of gross specimens. We’re onto something here, keep an eye on MSI.

12. Molecular—Need I say More?

Image 9. Move over International Space Station, the folks at Thermo Fischer Scientific want to share their take on the Next Generation of molecular testing. (Source: The Pathologist)

Same edition of The Pathologist, about 25 pages back: a discussion on the value of molecular Next Generation Sequencing. I’ve already bored half of you, wait! Come back. I agree with you, you can only call it Next-Gen so many times before a whole generation of laboratorians get bored of talking about new tumor markers or mutations. But what’s happening with NGS testing that you should know? Simply put, there are NGS analyzers that are faster, with smaller footprints, combined with smarter software that is making molecular more feasible for laboratories that used to shy away from the notion of including NGS or LDTs in their lab testing menus. This means more labs, running more molecular, for more specific populations, in real time that can collaborate with that many more new colleagues while breaking silos—well just look up at #18, 17, 16, and 15!

11. Global Health

Image 10. From Dr. Razzano’s post on Lablogatory

Dr. Dana Razzano recently interviewed me for her global health series, and we got the chance to talk about the important intersection of laboratory medicine and global public health. Getting involved in a community—especially for those of us in healthcare—often includes a survey of what kind of health challenges you face. For some it’s access to clean resources like water, for others it’s a complex system of reimbursement and billing issues that complicate delivery of care, or even more basic assessments reveal high rates of local infections with preventable illness. But you can’t tackle infrastructure change, political reform, or vaccine education single-handedly. Global health is an increasing part of our global world and, if we stay true to our professional values, we should be at the forefront.

10. AI in Healthcare (part 2)

Image 11. Drawing to represent AI from my TEDx talk, Unrecognizable Medicine 2019, TEDxAUCMED

Oh I told you I’d come back to this. Some folks are still apprehensive about AI—that’s ok—I am too, but only because I want to make sure it’s done right. Don’t expect any Skynet stuff, we’re not going that deep. So let me tell you some of the things I got to see on the residency interview trail that piqued my interests. At one hospital system, I saw plans for their anatomic pathology department to go fully digital with augmented AI software to help score mitoses and other morphologic traits by 2025. At another institution, I saw plans for data mining historical free text pathology reports to predict and stratify future specimens before they even got signed out! At a third system, I saw the utilization of smart software to predict clinical lab values for a patient’s personalized reference range…pre-analytically! This stuff is coming in hot so watch for it! What AI-related advancements are you seeing in your neck of the lab?

9. Patient Consultation

Image 12. Courtesy of SUNY Upstate Pathology Department via Twitter, a newly renovated pathology residency review room and patient consultation suite for the dedicated purpose of this invaluable interaction.

Another thing noteworthy of my residency trail are institutions which are championing the face-to-face consultative role of the clinical pathologist in patient care. We, at the end of the day, are consultants to all; physicians and patients alike. And many in our field are celebrating this role by pushing the envelope toward a progressive and effective future for pathology and laboratory medicine at large.

8. Graphic Medicine

Image 13. My very first #pathdoodle – What do Pathologists do?

Graphic medicine is fantastic! I wish I could have discovered this years ago. Nevertheless, in the last two years I have sought out and read numerous pieces which bridge a significant gap between clinician and patient. And if we in laboratory medicine plan to reach patients more directly, we shouldn’t be afraid to come up with creative solutions to communicate with them. My (current) approach, #PathDoodles which I post occasionally on social media, attempts to explain concepts in pathology to the everyday lay person. What will you do to reach your patients?

7. Wellness Programs

Image 14. Anonymous survey responses to Dr. Saint Martin’s program from trainees at Loyola University Medical Center. (Source: The Pathologist)

Another interesting thing I encountered on the residency interview trail was the way in which different programs addressed the concept of wellness. Some did, some did not, but everyone discussed it. Because, after all, it is important; not just for residents and physicians, but medical lab scientists, support staff, and …yes… even administrators. Work and work-life stresses and balance take a psychological and emotional toll, and in order to be happy and healthy we need ways to strengthen our mental health along the way. Last year, Dr. Marissa Saint Martin won a 2018 award from the American Association for Physician Leadership for her work in preparing residency resilience and promoting wellness through structured curricula at Loyola Health System and Mount Sinai in Miami. She’s been featured with ASCP numerous times as well as in The Pathologist. It’s promising to see such strong support for residency trainees; keep an eye out for other praise-worthy programs this year!

6. Social Media

Image 15. It takes a new kind of clinician to serve a new kind of patient. How will you rise to meet the challenges on the horizon that we can’t predict yet?

You caught me. I can’t make any predictions about the future of health care delivery, education, or collaboration without touting the importance of social media. As a member of the official ASCP Social Media Team (Go #ASCPSoMeTeam!), I’m a proud contributor not only to the content that we publish online, but to the message that unifies and spreads our #StrongerTogether mantra. Social media is fantastic tool to reach new colleagues, spread new ideas, and make new advancements in both our field and in reaching people where they are.

5. Moving Out of the Basement

Image 16. Is this closer to a representative image of your lab than you’d wish? Don’t worry, you’re not alone. Basement labs are so last season. (Source: Seret Studios, Bridge Basement, Brooklyn NYC)

One of the most memorable interviews I had this season was with a transfusion specialist who recounted to me his memory of training in pathology during his early days of residency. Green and eager, he told me how he remembered being taken on a tour of the facilities to be shown his desk/work space and upon reaching an underground level of the hospital building a sign read ‘BASEMENT’ with an adjacent one ‘PATHOLOGY’ …he paused to say it out loud, “What’s a basement-pathologist?” We bonded over the stifled stereotypes in our work and shared stories of great and terrible lab spaces we’ve seen. Some programs are renovating, some (for better) are moving on up… How are your facilities?

4. The Pipeline Problem

Image 17. The …scope of a pathologist has changed over time (see what I did there?). Sure, lots of us push glass and diagnose entities on tissue samples with complex investigations and work up, but many more of us ensure quality laboratory efficacy, develop new cutting-edge tests, manage donor centers and transfusion protocol, address infectious or public health crises, and more! I think the more we celebrate our profession, the more will join and contribute to our #StrongerTogether culture!

Well I mentioned stereotypes. I’ve talked about it before.  You already know about shortages in pathology from physicians to lab scientists. And don’t get me started on pay—especially for lab workers and those in forensic path! But this is a topic I think we’re going to see a boon in media coverage in the coming years, starting now. Some of our awesome colleagues are talking about the “pipeline problem” from a myriad of angles: addressing medical student clerkships, exposure to laboratory workflow in school curriculum, advertising the infinite possibilities of careers within our profession…and more. CAP, ASCP, USCAP, and other professional societies have done amazing work in their due diligence to represent our field and advocate for the advancement of our work and image. A former CAP president once said, “Pathology is what a pathologist does,” and well, it’s a good start. Where do you see solutions to our pipeline problem?

3. PA’s and… CPA’s?

Image 18. Pathologist assistants work directly under the supervision of a pathologist in a similar way that physician assistants work with physicians. Clinical pathologist assistants help to determine the cause of disease through the examination of blood and other bodily fluids and tissues. (Source: UAB)

Now this, this is a cool concept and it’s the first time I’ve seen it. We all know and love our pathology assistants (PAs)—especially resident pathologists—as they make the training, education, and workload a better process for learning. They have awesome training and operate essentially as highly specialized clinicians in anatomic pathology. But what about the clinical, laboratory medicine side of things…? I recently saw a program advertised at the University of Alabama at Birmingham that trains clinical PAs for consultative and ancillary support roles to the clinical pathologist! Fantastic! Read more about it here! There are a growing number of DCLS (doctor of clinical laboratory science) professionals, now we’ve got a new pipeline to invite talented folks to work with us in a new way.

2. I’ll Have a Residency!

Image 19. Need I say more? What does the paper say?? Where am I going to end up? It’s a whirlwind of a season and a crazy system—once in a lifetime sort of adventure! Stay tuned, I’m sure I’ll have a post or ten about the next chapter of my career… (Image source: AAMC)

I have seen so many fantastic programs across the US these past few months, and so many decisions go into the way medical graduates rank programs to match into. To learn how the AAMC/NRMP matching system works, watch this video (maybe with some calming tea). We’ll see where I end up matching to, but I’m excited for the next chapter and to really dive into pathology even more!

1. You!

Obviously, the most important thing to keep an eye out for this year is you! Your goals, your ambition, your plans, your ideas and thoughts, and all the ways you contribute to our fantastic profession! I encourage you all to share, collaborate, and be creative with the ways in which we advance the future of laboratory medicine and continue to keep in mind that we do these things for our patients everywhere.

Thanks for reading, see you next time!

Constantine E. Kanakis MD, MSc, MLS (ASCP)CM completed his BS at Loyola University Chicago and his MS at Rush University. He writes about experiences through medical school through the lens of a medical lab scientist with interests in hematopathology, molecular, bioethics, transfusion medicine, and graphic medicine. He is currently a 2020 AP/CP Residency Applicant and actively involved in public health and education, advocating for visibility and advancement of pathology and lab medicine. Follow him on Twitter @CEKanakisMD

A New MLS Graduate's Experience

I wrote last as a student in the medical technologist program at NorthShore University Healthcare System in Evanston. Now, as my first post as a certified medical technologist, I wanted to share what the journey was like becoming certified, finding a job, and transitioning into the professional arena.

Throughout the program, I felt relatively confident in the material and what we were learning and applying in rotations. We took about 1000 tests over the course of the program – at least that’s what it felt like. When the ASCP BOC exam began peaking its head, I wasn’t too intimidated. To me, it was just another test.

The first step was registering for the exam. My intention was to take the exam the day after I graduated, but I was bad and waited one month prior to graduation to register (it can take up to 45 business days to process). Don’t do as I did! Thankfully, the process was quicker than expected and I was only delayed one week after graduation.

The last four weeks of my program were intimidating to say the least! We had cumulative finals in addition to simulated board exams. Therefore, my BOC exam studying began through preparing for these. One of the most valuable resources that I cannot recommend enough is LabCE by MediaLab. I first discovered LabCE through their manual UA and differential simulators, but then discovered that they have testing simulators which our program director used to create practice exams for subjects and for the BOC exam. Their questions range in difficulty and each one has an explanation, which presents a great way to study (at least for me). It helped me develop study guides on material I consistently got wrong or completely forgot.

Two weeks before my exam, I discovered the BOC CLS study guide. I immediately paid for overnight shipping and received it the next day. This turned into my main study tool – I do best quizzing myself, then reading up on topics I got wrong. I would be lying if I said I felt confident when I received that book and went through the first 50 questions. I felt incompetent. Despite my previous review and studying, I felt as if I discovered an entirely new language. The book is very detailed and covers everything from a to z for laboratory science, with some topics only being covered briefly in school. As time went on, the shock factor wore off and I continued to focus on the things I no longer remembered and believed were important.

Despite the endless hours studying, I felt that there was much left to cover and the night before my exam I remember feeling overwhelmed. There is only so much information the human brain can store without the hands-on experience that ingrains what you learn. Throughout the test I felt as if I were failing, something that seems to be common place among BOC test takers. When it was time to see my score, my hands became clammy. Despite the suspense, I passed! When I received my scores later, I did much better than expected!

So, my concluding advice while preparing for the BOC exam is to focus on summarizations of your notes and to review all your formulas throughout your program. Go through as many practice exams as possible to help you see where you’re lacking and to prepare you for the wording on the BOC exam. Throughout my program, I would type up one to two-page notes for exams for later review. These were helpful when I had to go back and review things I did not remember. Additionally, despite the amount of studying you do, there is bound to be information you will not know and that’s okay. You know more than you think you know and through review you will only increase the recoverable information that is already in your head.

Lastly, I wanted to speak about the process of a new grad finding a job and transitioning from a student to a health professional. As I went through rotations, my passion for each specialty changed. At first, I wanted to be a generalist because I wanted to be more marketable and do everything. Then it was blood bank, then micro, and then came molecular (yay!). I began my job search about 2 months before graduation, and applied for those jobs about a month and a half before graduation. Being a soon-to-be new grad, I knew that I might not end up in the exact field I desired right away (which was molecular). I applied for mostly blood bank, micro, and molecular jobs – as these were of the most interest to me.

I applied for about 6-7 jobs in total and I ended up discovering, and eventually obtaining, my current position as an HLA molecular scientist at Northwestern’s transplant lab in Chicago. Throughout the interview process, being 100% honest of what you do and don’t know is the most important advice. Most employers ask a lot of detailed questions only to gauge where they need to start in your training. A good rule of thumb to remember is that if you’re a new grad being interviewed, then the employer is already okay with the fact that you don’t have much experience or knowledge of the specialty.

Before starting, a lot of people warned me about specializing immediately after graduating. While I hear their concerns, for me I plan on staying in the molecular field for the rest of my career – there are many opportunities and molecular is only becoming more and more advanced/widespread.

Now that I am 2 months into my job, I have fallen in love with it. There is endless opportunity to continue learning and to challenge myself. Walking into this specialty, I had two HLA lectures and nothing more. While my first month and a half mostly consisted of DNA isolation and cell lineage DNA isolation for chimerism tests, I have finally started training on an assay and data analysis for engraftment monitoring (chimerism). As a new grad in such a specific specialty, I have accepted that there will be a large learning curve. My advice is to keep your mind open to learning new things and fuel your motivation to learn more and more. Never stop asking questions and never turn down resources others hand you that have helped them.

As I gain more experience in the HLA world, I plan on writing articles tailored to this field and sharing what I learn. I hope my experience as a new grad helps others approaching this new time in their lives and gives them a sense of direction/confidence.

-Ben Dahlstrom is a recent graduate of the NorthShore University HealthSystem MLS program. He currently works as a molecular technologist for Northwestern University in their transplant lab, performing HLA typing on bone marrow and solid organ transplants. His interests include microbiology, molecular, immunology, and blood bank.

By the Numbers: Injuries and Exposures in the Lab

Finding information about the number of Laboratory Acquired Infections (LAIs) and other laboratory injuries in the United States is difficult. Many events are not reported, and of those that are reported at the facility level, only some are required to be reported to national agencies. A report by the CDC cites four studies that collectively identified 4,079 LAIs resulting in 168 deaths occurring between 1930 and 1978. Again, those are just the reported occurrences, and the data says nothing about other injuries in the lab such as slips, trips, and falls, or lacerations.

The Bureau of Labor Statistics (BLS) provides benchmark injury and exposure data for clinical laboratories, but this information too, is limited to that which is reported. That said, the information may still be of value—it can be used to compare your lab’s reportable injury data to labs across the nation. This can provide one form of assessing your overall lab safety.

The BLS provides annual clinical lab workplace injury data in the form of a rate. That rate is obtained via a calculation:

(Number of injuries and illnesses X 200,000) / Employee hours worked = Incidence rate

Incidence rates can be used to show a relative level of injuries and illnesses among different industries and within the same industry. Because a common base and a specific period of time are involved, these rates can help determine both problem areas and progress in preventing work-related injuries and illnesses. In this equation, the number of injuries and illnesses comes from your log of work-related incidents reported on your department’s OSHA 300 log. The worked hours from your lab should not include any non-work time (even if it is paid) such as vacation, sick leave, or holidays. You can estimate the worked hours on the basis of scheduled hours or eight hours per workday. The 200,000 is a constant—it represents the equivalent of 100 employees working 40 hours per week, 50 weeks per year, and provides the standard base for the incidence rates.

It takes time for national annual injury and illness rates to be calculated, so the most recent data from the BLS today is from the year 2018. Back in 2014 the rate for clinical labs was 3.4, and in 2015 it went down to 3.3. In fact, the BLS lab data shows a steady decline in reported incidents over the past twelve years. The most recent rate is 3.1. That’s good news that could mean that lab safety awareness is improving across the country.

How does your laboratory data compare to national numbers? It’s a good idea to use the calculation so that you can see how your lab is doing. If your injury, exposure and illness numbers are on the rise, it’s time to take action. Look for the causes of the incidents and implement methods of prevention. If you see a pattern of the same type of incidents, you may need to execute a safety stand-down around that specific process.

Now that you can compare your reportable data to a benchmark, what about the non-reportable events in your lab? They should get attention as well. Events like closing a finger in a drawer or cutting a finger on a clean microtome blade should always be reported to lab management and the occupational health department, but they may not be required to be reported elsewhere. They still need the same follow-up in the lab, however, and as a lab safety professional, you should be an integral part of the process to engender safety success in the lab.

While there is no national data to compare to for all types of lab injuries and exposures, it is still helpful to collect the information and calculate your lab’s rate. You can keep track of that overall rate and look for trends and make improvements on all incidents in the laboratory. Be sure to promote a culture of transparency and non-punitive reporting so that all lab accidents can be documented.

Knowing how many LAIs and other injuries in laboratories are occurring across the nation is no easy task. The best place to begin is within your own lab. Collect the data and become more familiar with this indicator that can guide you to the right path to improved employee safety in the lab.

Dan Scungio, MT(ASCP), SLS, CQA (ASQ) has over 25 years experience as a certified medical technologist. Today he is the Laboratory Safety Officer for Sentara Healthcare, a system of seven hospitals and over 20 laboratories and draw sites in the Tidewater area of Virginia. He is also known as Dan the Lab Safety Man, a lab safety consultant, educator, and trainer.

Patient Advocacy: Introduction

“I do not really understand what pathology is,” I said during my first round of interviews at ASCP. “In fact, I have a website page in front of me that describes it and I still do not really get it. I want to be upfront about that before we go any further in my interview process,” I followed. Needless to say, I got the job, but that experience really stuck with me. As I learned more and more about pathology and laboratory medicine, I was amazed that I had not known more about it. I had been to the doctor all my life, I had received some serious diagnoses, and I thought I was pretty well-versed in what my medical care entailed.

In the last few years that I have been with ASCP I have become passionate about educating patients about the role the medical laboratory plays in patient care. Without that understanding, patients will be less empowered and less likely to advocate for themselves. Their family doctors might order tests that they do not want or not order ones they that do. They might not understand certain results, which means that they are less likely to take an active role in their care. The more we education patients and their caregivers about pathology and laboratory medicine, the higher quality health care we create. Educated patients are empowered patients and it is imperative that education includes the laboratory.

Through directing the ASCP Patient Champions program, I have been fortunate to meet incredible patients, all who have some understanding of the role the laboratory played and plays in their care. Hearing them say that without the laboratory, they would only be a memory, is incredibly powerful and humbling. The active role these patients play in their care has allowed them to be more resourceful and more hopeful. For some of them, seeing their own slides has been a cathartic experience because they could suddenly see the enemy they were fighting. Others are now educating new patients about their lab tests and taking time from their own busy schedules to volunteer at hospitals and clinics.

It can also be an inspirational experience for laboratory professionals and pathologists to hear how they impacted a patient’s life. I have personally shed many tears when interviewing patients so I can only imagine what it is like to hear from someone whose life you have impacted, let alone meet them in person. It can also really help patients to have their diagnosis be explained by someone working in the lab and to understand why their blood is drawn or why a biopsy is needed.

This new series on Lablogatory called Patient Advocacy, will explore the topic of patient advocacy from laboratory professional, pathologist, and patient perspectives. Each month, you will hear how patient interactions have impacted lives and what we can do to make more people aware of the crucial role the medical laboratory plays in patient care. You are all changing and saving lives every day. Let’s learn together how we can increase our patient advocacy to help them even more.

-Lotte Mulder, EdM, is the Senior Manager of Organizational Leadership and Patient Engagement at ASCP. She earned her Masters of Education from the Harvard Graduate School of Education in 2013, where she focused on Leadership and Group Development. After she graduated, Lotte started her own consulting company focused on establishing leadership practices in organizations, creating effective organizational structures, and interpersonal coaching. She has worked in Africa, Latin America, Asia, and the U.S. on increasing leadership skills in young adults through cultural immersion, service learning and refugee issues, and cross-cultural interpretation. She is currently working toward a PhD in Organizational Leadership.

Recognizing Disruptive Innovation in Global Health

One of the challenges of providing healthcare to patients of any type is “staying current” or “keeping up with the literature.” This can be especially challenging in the diagnostics laboratory where novel or unique approaches to a given test or test method or disease may show early promise but have no clinical utility, be too expensive, or not actually significantly change work-flow and/or patient value to justify implementation. On the other hand, sometimes a technology or test which is in development or approval can be so anticipated that clinicians and laboratorians are frustrated that it is not yet available.

In global health, there is a different problem that is encountered every day. There are technologies and tests that are approved, have documented clinical utility, and add great value to patients but they are simply not available because of supply chain, cost, administration, or geography. In such situations, the practitioners in these settings face extreme frustration—especially with stock-outs—and can become jaded and non-dependent on laboratory testing as part of care. This latter issue is a major challenge in cancer care where cancer diagnoses are required before treatment can begin; yet, in a large number of countries, access to cancer diagnostics routinely is not available. It is to that end that ASCP along with a whole host of NGO, industry, academic, and government partners are making great efforts to improve cancer care in each part of the continuum.

In this environment, however, disruptive innovations are, in fact, much easier to recognize as forthcoming. In the early 2000’s when I was working and traveling in Malawi, our project had a landline in the hospital to call the landline at the doctor’s house for issues overnight with patients. This required 24-hour nurses to be physically in the ward, tied to the phone and the patients. Landlines were expensive to install, had a very long waiting list to be installed, and, for the most part, the majority of the population in the country had never had a phone line in their dwelling. By the mid-2000’s, our project had one or more cellphones (as did the nurses) and communications through texting were nearly constant (especially since it was less expensive than making a phone call). By 2010, cell phones were ubiquitous in Malawi (and almost everywhere else in Africa) and there was no demand for landlines. Although this is a commonly used example, consider the adoption of cellular telephones and now smartphones in the US compared with Africa. There was push back, denial, avoidance, and even refusal to use them because there was an existing, well established system of landline communication.  If you want to install cable television and internet in your home as late as 2016, you were often required to bundle with a landline. The point is that the adoption pattern was significantly different because there was a pre-existing competitor with the new technology although—clearly—the new technology was superior.

Now consider a woman of 35 years who has a breast mass on mammogram in downtown Boston today. She will likely have an imaging study with immediate ultrasound and fine needle aspiration and/or core biopsy subsequent. A pathological diagnosis will be issued within 3 to 4 business days (or sooner) which includes a histological diagnosis along with hormone receptor status and Her2 staining. She will see a clinician likely within a week for a positive cancer diagnosis and a treatment plan will be decided upon and executed. If we consider a similar woman in downtown Nairobi, Kampala, or Lagos, they may, in fact, have a similar experience because of the recent efforts globally to improve cancer awareness, diagnosis, and treatment. There may be some delays (reports may take several weeks), potential stock-outs, etc. but, in these major cities, the services might exist. They are likely, however, provided in private clinics, will cost a premium, and may or may not have any guarantees about quality.

The reality, however, is that the vast majority of women in the US or Europe who present with breast cancer do so at a very early stage because of active screening programs which include mammography. The vast majority of women in low- and middle-income countries (LMICs) present with later staged disease because of lack of screening. The latter group of women, however, often live in rural conditions and/or poverty conditions such that seeking care for a breast mass (of any size) will require them to spend time and money to travel to one of the major cities and attempt to access services. With this situation, many of these cancers are detected by the health system at a late stage where curative therapy windows have been missed.

Onto these observations let’s now overlay access to a test for a breast mass that can be performed on a fine needle aspiration biopsy and resulted in ~4 hours which will provide a diagnosis of cancer (or benign) along with prognostic features directing treatment. If we consider the woman in Boston, we may see such a test providing an incremental improvement in care because billing systems, litigation fears, compliance requirements, or accreditation standards still include routine histology and immunohistochemistry to be performed on a tissue biopsy. To some degree, the test may be rejected because it is adding a cost over the standard costs without adding value (other than speed) to the results. However, for the woman in the rural village who likely has access to a community health worker, access to such a test could mean that she starts oral therapy the same day she has the health visit without ever having to leave her village. We have now removed the journey to a clinic that can performed a biopsy, the costs associated with that travel, the time lost while traveling and waiting for a result, and removed the risk that this is not breast cancer—which would mean all the time and money were wasted. For this woman, enormous value is created for her with a test that is performed same day with immediate results.

This concept of point-of-care (POC) cancer diagnostics would arguable meet resistance in the US or European system because of competition with existing systems and other issues as mentioned previously. In an LMIC setting, as there may be no competition, such an innovation would sweep the system and become standard of care—almost regardless of cost. This last bit is very important because traditional systems for performing histology and IHC are complex, costly, and require multiple highly trained individuals to get a quality result. If that process costs $75 to $100 US dollars (to the health system) to provide and, for the individual patient, $10s to $100s of dollar for the travel, lodging, and lost wages, the cost of such a test could, in a stable, high-income country (HIC) market, fetch a hefty price. However, if such a test is priced at $25 to $50 USD (half the cost of the current system excluding the travel), the immediate replacement of the old system with this new system for the given indication must and will occur. This uptake is amplified in an LMIC when the POC test moves to the patient in a geographically distributed process. Breast cancer is an obvious target for such an approach because the tumors are easily accessible, the disease is quite common globally, and the primary therapies are very inexpensive. Could such a test have an impact in an LMICs for bone marrow-based, lung, bladder, colon, prostate, liver, kidney, or soft tissue tumors? The answer to that question lies in the availability of therapy, incidence of disease, and access to radiological equipment rather than availability of the actual POC device. That is, once you have a POC test for one cancer, creating a subsequent POC test for another cancer is a surmountable technical hurdle. But will such a test be able to have an impact because of the alignment of the other factors? It is likely that as you are reading this sentence, you have thought of a few yourself but there are certain cancers where you are likely thinking, “not possible”.

For breast cancer, two such POC approaches are coming down the pipeline. The first is the Cepheid GeneXpert Breast STRAT4 assay which measures quantitative RNA (qRNA) for ESR1, PGR, ERBB2, and MKi67. These four assays are surrogates for standard immunohistochemical staining for ER, PR, Her2, and Ki-67, respectively. In a series of published and in press feasibility and validation studies, the qRNA assay is essentially equivalent to IHC. There are nearly a dozen studies of this new testing cartridge using formalin-fixed, paraffin embedded (FFPE) tissue throughout Africa where the test is being compared to standard IHC. However, in at least one site, the test is being performed directly on FNA material. The second test is from the laboratory of Dr. Sara Sukumar at Johns Hopkins which uses a set of DNA methylation markers that can separate benign from malignant disease on FNA using only 10 markers. By combining these two approaches (benign vs. malignant followed by STRAT4 for positive tumors), a diagnosis of malignant breast disease with prognostic factors for treatment could be obtained in less than 4 hours.

Let’s jump forward to the point in time when both of these POCs are available (or, in fact, any POC for cancer is available). How would they change the approach to breast or other cancer in an LMIC? Because both tests require only an FNA of a mass and because tumors of the breast and other organs today are often late staged, community health workers could be trained to evaluate patients with masses, perform the sampling, and run the test in a remote village. Regardless of stage, starting a breast cancer patient on estrogen receptor antagonists can provide palliative relief or pre-surgical treatment. As a population down stages—which occurs as community health workers begin routine screening—the testing can triage benign and malignant disease at a fraction of the cost for both the system and the patient. Based on population epidemiology, nearly exact costs for these services can be predicted for a population and stock outs can be avoided. Corollary note: Only for those cancers for which you HAVE a POC.

How would these tests change the approach to breast cancer in an HIC? There would likely be resistance at many levels but, eventually, the relatively low cost and the increased patient value would allow the tests to replace or displace standard diagnostics. Without complete replacement, there could, at a minimum, be multimodality redundancy which increases quality. However, the tests would find purchase within the system because in some settings their cost and added value would make any other choice impossible.

For both settings, we can now add other market entrants, other tests for other cancers, and a generalize increased in cancer awareness in the community, all of which would increase demand, improve morbidity and mortality, but decrease costs. Such a situation would be highly valued by the patients and, therefore, is the most important eventuality as this disruption ensues. Recognizing forthcoming change is sometimes hard and sometimes easy; however, accepting and embracing forthcoming change in healthcare can lead to best outcomes for our patients—the central mission of ASCP.

Dr. Milner has no financial disclosures regarding this blog post and has received no fiscal or in-kind support from any entity, named or otherwise, that involves this blog post.

References

  1. Wu NC, Wong W, Ho KE, Chu VC, Rizo A, Davenport S, Kelly D, Makar R, Jassem J, Duchnowska R, Biernat W, Radecka B, Fujita T, Klein JL, Stonecypher M, Ohta S, Juhl H, Weidler JM, Bates M, Press MF. Comparison of central laboratory assessments of ER, PR, HER2, and Ki67 by IHC/FISH and the corresponding mRNAs (ESR1, PGR, ERBB2, and MKi67) by RT-qPCR on an automated, broadly deployed diagnostic platform. Breast Cancer Res Treat. 2018 Nov;172(2):327-338.
  2. Wasserman BE, Carvajal-Hausdorf DE, Ho K, Wong W, Wu N, Chu VC, Lai EW, Weidler JM, Bates M, Neumeister V, Rimm DL. High concordance of a closed-system, RT-qPCR breast cancer assay for HER2 mRNA, compared to clinically determined immunohistochemistry, fluorescence in situ hybridization, and quantitative immunofluorescence. Lab Invest. 2017 Dec;97(12):1521-1526.
  3. Downs BM, Mercado-Rodriguez C, Cimino-Mathews A, Chen C, Yuan JP, Van Den Berg E, Cope LM, Schmitt F, Tse GM, Ali SZ, Meir-Levi D, Sood R, Li J, Richardson AL,  Mosunjac MB, Rizzo M, Tulac S, Kocmond KJ, de Guzman T, Lai EW, Rhees B, Bates M, Wolff AC, Gabrielson E, Harvey SC, Umbricht CB, Visvanathan K, Fackler MJ, Sukumar S. DNA Methylation Markers for Breast Cancer Detection in the Developing  World. Clin Cancer Res. 2019 Nov 1;25(21):6357-6367.

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-Dan Milner, MD, MSc, spent 10 years at Harvard where he taught pathology, microbiology, and infectious disease. He began working in Africa in 1997 as a medical student and has built an international reputation as an expert in cerebral malaria. In his current role as Chief Medical officer of ASCP, he leads all PEPFAR activities as well as the Partners for Cancer Diagnosis and Treatment in Africa Initiative.

From Safety Eyes to X-Ray Vision

In the Immunohistochemical stain lab, Rory made up his special stains under the chemical fume hood. One of the reagents he used was hydrochloric acid. At the end of each month there was usually a little bit of acid that needed to be disposed of as waste. He poured the waste acid into a glass jar and labeled the jar as “waste HCl.” He then carried the jar through the door to the room next door where there was an acid storage cabinet. That was where the contracted chemical waste vendor picked up other wastes from the lab.

Lydia was working the night shift in blood bank when she was changing the waste container on the automated type and screen analyzer. She splashed some waste into her eye when pulling the container out of the analyzer. She rubbed some water from the restroom sink in her eyes and decided not to report the incident as she was already in trouble with the supervisor for her continued absences.

I often talk to Lab Safety Professionals about using their “Safety Eyes” while performing their duties. It’s a latent ability we all have and can develop with some practice. With it, one can walk into a laboratory and quickly see safety issues and even make a swift assessment of the overall safety culture. Much of what can be seen using that super-power belongs to the lab’s physical environment- that which lies on the surface and should be visible to all. But sometimes there are deeper issues, those that may be more hidden. With practice, one might easily spot incorrect use of PPE, unlabeled chemicals or trip hazards. But how do you spot those other safety issues that can be just as dangerous- or even more so? How can your Safety Eyes ability be honed into something more powerful….like X-ray vision?

In the first scenario above, you may see nothing wrong, especially if you’ve performed that process yourself for years. One week later the EPA inspector came in for a laboratory waste audit, and they cited the lab for moving waste from the point of its generation to another area which was not designated as a Central Accumulation Area (CAA). Hazardous (chemical) waste cannot be moved to another location outside the line of sight of its generation point unless that other area is treated a CAA.

In the second scenario Lydia woke up the next day because her eye began to burn. She went to the emergency room and told her story. Because she missed the window of opportunity for proper treatment of an unknown source exposure to biohazards, she had to undergo long-term treatments which involved strong medications which have unpleasant side effects. She also had to be tested regularly for Hepatitis and HIV.

Some people you may know in the lab have been performing unsafe acts for years with little or no known consequences. Have they been doing the right thing or have they been lucky? What will it take to correct those unsafe actions? A fine? An exposure or injury? Hopefully not. Sometimes the reason unsafe acts occur is that staff is unaware of the regulations or the potential consequences. Influencing others’ safety behaviors is another more subtle super-power of the Lab Safety Professional, but it can be both important and useful.

As a safety professional, make sure you develop your basic super powers- your Influence and your Safety Eyes- but also be sure to augment what you already know how to use. Learn to use some X-ray Vision. Look more deeply for those processes and actions that may have been in place for years. It is not too late to make a change and prevent an incident that was years in the making.

Dan Scungio, MT(ASCP), SLS, CQA (ASQ) has over 25 years experience as a certified medical technologist. Today he is the Laboratory Safety Officer for Sentara Healthcare, a system of seven hospitals and over 20 laboratories and draw sites in the Tidewater area of Virginia. He is also known as Dan the Lab Safety Man, a lab safety consultant, educator, and trainer.