The Fellow on Call: The Heme/Onc Podcast

We continue on our cytopenias journey, this time talking all about anemia. This is a high yield topic for anyone who sees patients, as this is something we will all see. Determining the acuity of the anemia is the most important first step. Acute drop in hemoglobin? Consider active bleeding or hemolysis. Dilutional anemia (a drop in hemoglobin following fluid resuscitation) is also on the differential but should be a diagnosis of exclusion.Remember that we normally transfuse at a hemoglobin level of 7g/dL. If the patient has active cardiac issues, we transfuse at 8g/dL. Anemia Severity> 10g/dL = mild 7g/dL to 10g/dL = moderate 4.5g/dL to 7g/dL = severe, especially if acute 1g/dL to 4.5g/dL = these are almost always chronic if patients are conscious. Think about chronic blood loss or nutritional deficiency.History: Ask about nutrition, melena, hematochezia. Note that a small amount of blood can change the color of the urine, so beware of contributing rapidly developing anemia to hematuria.Physical Exam: Check the flanks and thighs for bruising. Feel for an enlarged spleen.Work Up: Smear—to evaluate for spherocytes, schistocytes, bite cells, etc.LDH—will be markedly elevated if blood is actively hemolyzingDAT/Coombs testing—to screen for AIHA, note that there is a high false positive rateType & screen Haptoglobin—sensitive but non-specific marker for blood breakdownReticulocyte count Macrocytic Anemia: Consider copper, B12, folate deficiency, reticulocytosis. Note that chronic zinc excess can cause copper deficiency. Microcytic Anemia: Consider iron sequestration or deficiency, lead poisoning, thalassemia. Normocytic Anemia: Usually multifactorial. Consider low erythropoietin level from chronic kidney disease or early iron deficiency anemia.Please visit our website (TheFellowOnCall.com) for more information Twitter: @TheFellowOnCallInstagram: @TheFellowOnCallListen in on: Apple Podcast, Spotify, and Google Podcast

One of our most common consults in hematology is teams seeking guidance for workup and management of thrombocytopenia. In this episode, we cover our approach to this hematologic conundrum. Major Points Covered:Thrombocytopenia is defined as a platelet count <150K- Mild: 100-150K- Moderate: 50-100K- Severe: <50K- We get really worried when <20K (risk of spontaneous bleeding) What to ask in history and in chart review: - How quickly did the platelets drop - this is just as important as the absolute number; platelets may still be “normal” but have dropped significantly!- Mucosal bleeding? Menstrual bleeding?- Rashes?- Infections/Meds/Toxins?- Constitutional symptoms- Weight loss Our approach to a differential diagnosis - analogous to everyone’s favorite approach to renal AKI: “pre”, “intra,” and “post”:Pre: Infections/Meds/Toxins- 1st: HIV, Hepatits - 2nd: EBV, CMV, Histoplasmosis Intra: Primary bone marrow failurePost: Destructions/consumption/splenomegaly (Cirrhosis, too)- DIC- ITP- TTP - Platelet clumpingWorkup: - Smear - helps to quickly rule in or rule out a lot of the post-BM issues that are emergencies!- Citrated platelet count (to rule out platelet clumping)- Repeat CBC- Coags (PT/PTT/INR)- Fibrinogen- HIV serologies - Hepatitis B/C serologies- +/- Haptoglobin (note: in liver disease, you can have low haptoglobin) - Don't send SPEP/IFE!- If there is no abdominal imaging, consider abdominal ultrasound to evaluate for cirrhosis and/or splenomegaly References: https://www.sciencedirect.com/topics/medicine-and-dentistry/hypersplenism (Textbook of Gastrointestinal Radiology, 3rd edition 2008)- 90% of platelets in spleen at one timehttps://pubmed.ncbi.nlm.nih.gov/29978544/ (J Thromb Hemostasis 2018)- Platelet threshold for bleeding riskhttps://www.bjanaesthesia.org/article/S0007-0912(18)30753-0/fulltext#fig1 (British Journal of Anesthesia 2019)- Perioperative thrombocytopenia (Look at Figure 1)https://ashpublications.org/blood/article/131/8/845/104418/How-I-treat-disseminated-intravascular-coagulation (Blood 2018) - DIC with normal fibrinogen (Look at case 1, Table 2 shows good diagnostic criteria)Please visit our website (TheFellowOnCall.com) for more information Twitter: @TheFellowOnCallInstagram: @TheFellowOnCallListen in on: Apple Podcast, Spotify, and Google Podcast

Not to be confused with “carcinoma of unknown primary,” in this episode of metastatic disease of “origin TBD”, we discuss the workup of a mass noted incidentally on imaging. This is a very high yield topic often faced on solid oncology consults! Major Points Covered:Mass found incidentally on imaging → we need to stage alwaysInitial Workup:Reasonable to get CBC, CMP, UA, PSA (if male)Low blood counts, maybe marrow involvementCr elevated concern for obstruction possiblyLFTs elevated concern for mass in the biliary/pancreas regionUA w/ hematuria → maybe bladderBut bottom line you’re gonna get a scan, which scan to get though?Recommend referencing NCCN guidelines to determine additional staging scansCreate an account on nccn.org and look at guidelines by tumor typeNot all cancers require a PET/CT scanThere are newer modalities for imaging other than FDG PET including PSMA PET (prostate), Auxumin PET (prostate), and DOTATE PET (neuroendocrine)Certain cancers can be diagnosed on imaging alone (RCC and HCC)Some cancers require Brain MRI for stagingWhat to biopsy?FNA often adequate for solid tumors but may need core if non diagnostic Need core or ideally excisional if highly concerned for lymphomaAlways try to biopsy the site that will upstageDistant lymph nodes or other metastatic sitesWhat about tumor markers?We use this for treatment monitoring, not for diagnostic purposesImportant to establish a baseline to follow, special circumstances for diagnostic purposes to consider below:PSA in male if concerned about prostate cancerAFP helpful if concerned for HCC → liver masses in a cirrhoticAFP and b-HCG if concerned for testicular → young or middle aged male with mediastinal massMolecular testing not necessarily needed at the time of biopsy Please visit our website (TheFellowOnCall.com) for more information Twitter: @TheFellowOnCallInstagram: @TheFellowOnCallListen in on: Apple Podcast, Spotify, and Google Podcast

Heme Path Capstone Pt. 2 PearlsIn this episode, we continue our conversation with guest, Dr. Emily Mason, hematopathologist at Vanderbilt University Medical Center (Nashville, TN), as we apply all that we have learned in our Heme Path series. This time, we talk about a patient with a new leukocytosis, fevers, and easy bruising; and our approach to workup and management. Reminder: While these episodes may seem a little more in-depth than the prior Heme Path episodes, simply break down the conversation into the components we have discussed already and you will be amazed at how much you actually know - we promise!ELN Risk Stratification: https://www.researchgate.net/figure/ELN-2017-risk-stratification-of-AML-by-genetic-abnormalities-Adapted-from-Dohner-et_fig1_334634713original paper: https://dx.doi.org/10.1182%2Fblood-2016-08-733196Please visit our website (TheFellowOnCall.com) for more information Twitter: @TheFellowOnCallInstagram: @TheFellowOnCallListen in on: Apple Podcast, Spotify, and Google Podcast

Heme Path Capstone Pt. 1 PearlsIt’s time to put all you have learned in our Heme Path series to the test! Listen in as our guest, Dr. Emily Mason, hematopathologist at Vanderbilt University Medical Center (Nashville, TN) sits down with us to discuss the approach to diagnosis and workup of a new enlarged lymph node. While these episodes may seem a little more in-depth than the prior Heme Path episodes, simply break down the conversation into the components we have discussed already and you will be amazed at how much you actually know - we promise! Please visit our website (TheFellowOnCall.com) for more information Twitter: @TheFellowOnCallInstagram: @TheFellowOnCallListen in on: Apple Podcast, Spotify, and Google Podcast

Molecular Testing PearlsIn Part 4 of our Heme Path series, we thoroughly examine the details of molecular testing and how it relates to hematologic and oncologic malignancies I. Molecular Testing BasicsA. Provides a means of assessing patient’s genotypes, specifically at smaller changes in the genetic information B. How is it performed?1. Polymerase chain reaction (PCR)-based testing, which involves using a specific primer that is complementary to the area of interest on the patient’s DNA2. PCR can allow for both amplification and quantification of gene of interest C. Can look for either single gene mutations (faster) or a panel of mutations (slower but more information) also known as NGSII. Clinical Utility of Molecular TestingA. Very useful in risk stratification based on the mutations noted (some mutations are unfavorable and some are favorable)B. Certain genetic mutations have drugs that are effective against them, therefore provides information about targeted therapeutic options C. In hematologic malignancies, can be used to also assess response to treatment1. You can determine minimal residual disease or MRD2. Can look for a gene mutation that was present in the original cancer clone and see if there is any amount of residual cancer left over on the order of 1 in a million cellsD. In solid cancers, used to determine presence of genetic changes that have prognostic and targeted treatment implications1. BRAF V600E mutation in melanoma → BRAF inhibitor pill treatment2. EGFR mutation in lung cancer → EGFR inhibitor pill treatmentIII. How is molecular testing different than FISH?A. Both require choosing probes and understanding what you are looking for before running the testB. FISH (discussed in part 3!) reports out of 200 cells and provides information about only larger kilobase sized genetic changes (translocations, inversions, deletions)C. Molecular testing analyzes a much larger number of cells and can detect changes at the single base pair level. Much more detailed and microscopic evaluation of genetic changesIV. Single Gene Molecular TestingA. Look for a specific gene mutation (i.e. EGFR for lung cancer, BRAF for melanoma, FLT3-ITD for AML)B. Pros: 1. Faster turnaround time 2. Has a higher resolution and effective for detecting MRDB. Cons:1. Only looks for one genetic mutation as opposed to a panel like in NGS2. Some diseases ideally require understanding of multiple mutations not just one for prognostication and treatment planningV. Next Generation Sequencing (NGS)A. Allows to sift through a larger part of the genome to identify a panel of mutations B. Panel of mutations chosen is based on the clinical context1. For example: NGS for acute myeloid leukemia is much different than NGS testing for lung cancer as each cancer has a much different genetic mutation profileC. Overview of technical aspects of running NGS1. Massively parallel sequencing meaning that many tiny primers are used and the areas that primers encode may be overlapping2. A computer takes all of the smaller pieces and puts them together to determine the correct sequenceD. Pros:1. Gives us an understanding of many different mutations present based on the panel chosen2. Again, this has both prognostic and predictive treatment implicationsE. Cons:1. May find mutations of undetermined significance meaning we currently do not understand how these mutations will affect prognosis and treatment decisions2. Very time consuming (~2-4 week turnaround time)3. CostlyReferences:1. https://jamanetwork.com/journals/jamaoncology/fullarticle/2734828 - Quick overview of NGS2. https://ashpublications.org/blood/article/125/26/3996/34323/Minimal-residual-disease-diagnostics-in-acute - Look at table 1 to see the difference in sensitivity for MRD testing3. https://www.oncotarget.com/article/27602/text/ - Emphasizes prognostic relevance of EGFR mutations in NSCLC4. https://www.nejm.org/doi/full/10.1056/NEJMoa1612674 - Phase 3 trial showed that targeted treatment for EGFR mutation in NSCLC was superior to chemotherapy5. https://www.nejm.org/doi/full/10.1056/nejmoa1614359 - Phase 3 trial showed that targeted treatment of FLT3 mutation in AML improved outcomesPlease visit our website (TheFellowOnCall.com) for more information Twitter: @TheFellowOnCallInstagram: @TheFellowOnCallListen in on: Apple Podcast, Spotify, and Google Podcast

In Part 3 of our Heme Path series, we break down the basics of immunohistochemistry (IHC)Episode contents: - What is immunohistochemistry? - What are the pros and cons? - How do we use this clinically? ****Have some time and want to make some extra money? Get paid to participate in market research surveys: https://affiliatepanel.members-only.online/FOC_24?utm_campaign=FOC&utm_source=email&utm_medium=email** Want to review the show notes for this episode and others? Check out our website: https://www.thefellowoncall.com/our-episodesLove what you hear? Tell a friend and leave a review on our podcast streaming platforms!Twitter: @TheFellowOnCallInstagram: @TheFellowOnCallListen in on: Apple Podcast and Spotify

In Part 2 of our Heme Path series, we get into the details of cytogenetics (conventional karyotype and FISH)Episode contents: - What is "cytogenetics"? - How do we use cytoenetic information clinically? - What is the difference between the conventional karyotype and FISH? ****Have some time and want to make some extra money? Get paid to participate in market research surveys: https://affiliatepanel.members-only.online/FOC_24?utm_campaign=FOC&utm_source=email&utm_medium=email** Want to review the show notes for this episode and others? Check out our website: https://www.thefellowoncall.com/our-episodesLove what you hear? Tell a friend and leave a review on our podcast streaming platforms!Twitter: @TheFellowOnCallInstagram: @TheFellowOnCallListen in on: Apple Podcast and Spotify

In Part 1 of our Heme Path series, we break down the logistics and applications of flow cytometry.Episode contents:- What is flow cytometry?- How do we use this to identify cells?****Have some time and want to make some extra money? Get paid to participate in market research surveys: https://affiliatepanel.members-only.online/FOC_24?utm_campaign=FOC&utm_source=email&utm_medium=email** Want to review the show notes for this episode and others? Check out our website: https://www.thefellowoncall.com/our-episodesLove what you hear? Tell a friend and leave a review on our podcast streaming platforms!Twitter: @TheFellowOnCallInstagram: @TheFellowOnCallListen in on: Apple Podcast and Spotify

Thank you so much for checking out The Fellow on Call: The Heme/Onc Podcast. In this intro episode, learn more about our show and what you can expect. Please visit our website (TheFellowOnCall.com) for more information Twitter: @TheFellowOnCallInstagram: @TheFellowOnCallListen in on: Apple Podcast, Spotify, and Google Podcast