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#291 CBC Abnormalities Triple Distilled

August 25, 2021 | By

Enjoy this rapid clinical overview of CBC abnormalities based on Episode #167 LIVE! Common CBC Abnormalities Featuring Dr. Mary Kwok! Production & graphics by our very own and very talented Dr. Matt Watto!

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  • Written, Produced, and Hosted by: Matthew Watto MD, FACP; Paul Williams MD, FACP; Beth Garbitelli
  • Editor: Matthew Watto MD (written materials); Clair Morgan of

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Show Segments

  • Intro, disclaimer, guest bio
  • Approaching a mildly abnormal CBC, red flags
  • Build the diff, Fy(a-b-) phenotype
  • Physical exam and advanced testing
  • Polycythemia vera
  • Thrombocytopenia
  • Outro

Episode #167 CBC Abnormalities

Featuring Dr. Mary Kwok, production & graphics by our very own and very talented Dr. Matt Watto!

Approaching the Mildly Abnormal CBC

  • Look at the white count, hemoglobin, platelets, MCV, differential.  
  • Don’t knock the CBC: “I love my CBC like I love my morning coffee.” But also be judicious when ordering! 
  • Absolute count > percentages
  • Anytime you see blasts on a peripheral smear,  basophilia, or severely elevated counts, consult Heme-Onc right away (expert opinion)
  • Concerning if absolute eosinophil count of over 1500, less than that is less alarming (can be medication effect v.  allergy). Severe eosinophilia (>5000) associated with greater degree of tissue damage/disease severity (Lam 2021). 
  • Smoking is a very common cause (and reversible, Higuchi 2013) of unexplained neutrophilia
  • Basophilia is never normal (This raises suspicion for something myeloproliferative)
  • Quick associations: Lymphocytosis -?lymphoproliferative, Monocytosis – ?CMML, Basophilia – ?myeloproliferative or AML.
  • Repeat a CBC: especially if you can test a hypothesis (smoking cessation vs. medication stop)
  • One study suggests that effects from smoking cessation take 2-5 years to show complete resolution of changes in CBC (Van Tiel, 2002)

 Building Your Differential from the Differential

  • Harness the power of EMR and trend the CBC to see patterns
  • Look at the entire CBC (Don’t miss blasts!)
  • First rule-out: infection (chronic or acute)  v. medication effect
  • Some patients are Fy(a-b-) phenotype and labs will show ANC <1500. Formerly called ‘benign ethnic neutropenia,’ but non-whiteness should NOT be a medical condition (Merz 2021).  Lab test to confirm: phenotype of RBC
  • Rheumatologic process can be concomitant with neutropenia (ie: Felty’s Syndrome -RA, splenomegaly, and neutropenia with recurrent infections)

Physical Exam & Advanced Testing in Leukocytosis

  • Focus on: lymph node, spleen, infection
  • Sites of infection: skin breaks/sores, hardware in body, feet, joint pain
  • Bone Marrow Biopsy: for select patients
  • Lymphocytosis (ALC >5000) +/-  lymphadenopathy: consider flow cytometry

Flow Cytometry Basics

  • What is flow cytometry? In layperson’s terms “You take someone’s blood, and it’s tagged with all these different markers and then run through a machine, and the cells are plotted on a scatter plot. The pathologist identifies normal populations of cells but they’re really looking for abnormal cell populations. This can help you identify a clonal disorder, like a B-cell process or T-cell process, and can also pick up myeloid or lymphoid blasts” 
  • How to impress a consultant? Order flow cytometry if absolute lymphocyte count is high ahead of the heme-onc consult 

Polycythemia Vera Basics

Platelet Problems 

  • Questions to ask yourself: Is the thrombocytopenia isolated or not? Is this a platelet production problem or a platelet destruction problem?
  • Rule out hemolysis (bilirubin, LDH, haptoglobin, +/- direct antiglobulin test). Check HIV, and hepatitis C. Consider sending liver function tests, H. pylori, TSH, HCG (in women), SPEP/UPEP, B12 and folate depending on the clinical history (Tefferi 2005; Lambert 2017)
  • In the purple top tube,  there can be some clumping of platelets but this is detectable in the peripheral blood smear. Can give falsely low platelet count. Can run on a blue top (citrated) tube to avoid this (expert opinion)
  • ITP is a diagnosis of exclusion, must rule out HIV and Hep C,  B12 or folate deficiency, thyroid disorders, liver dysfunction (esp. cirrhosis), H. pylori, rheumatologic disorders, medications ( esp: heparin, chemo, antidepressants, antibiotics)
  • Thrombocytopenia is not an uncommon presentation of cirrhosis (Hancox 2013)


Listeners will review tops pearls from Curbsiders episode #167 LIVE! Common CBC Abnormalities

Learning objectives

After listening to this episode listeners will…

  1. Identify and interpret the key values (parameters) listed in a CBC with differential. 
  2. Recognize thrombocytopenia, generate a differential diagnosis, and order appropriate initial testing.
  3. Generate a differential diagnosis for erythrocytosis (polycythemia) and perform appropriate follow up testing.
  4. Generate a differential diagnosis, take a relevant history and perform appropriate follow up testing for leukocytosis and leukopenia. 
  5. Recognize who needs a referral to hematology for common CBC abnormalities.


The Curbsiders report no relevant financial disclosures. 


Garbitelli B, Watto MF, Williams PN. “#291 CBC Abnormalities Triple Distilled”. The Curbsiders Internal Medicine Podcast. Final publishing date August 23,, 2021.


  1. September 20, 2021, 11:12am Felipe writes:

    thank you so much!!! I'm a RN-preMed student working in an Internal Medicine Unit. ALL THIS MEDICAL CONTENT IS GOLD. :)

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