#167 LIVE! Common CBC Abnormalities with Mary Kwok MD

August 19, 2019 | By Matthew Watto, MD

Deep Dive on the CBC. Recorded LIVE at Walter Reed, Uniformed Services University.

Take a deep dive into common CBC abnormalities. We recorded LIVE at joint grand rounds between Walter Reed NMMC and Uniformed Services University with hematologist, Dr. Mary Kwok MD. Topics include: which parts of the complete blood count (CBC) are most important, interpreting the differential, when to order flow cytometry, who needs a hematology consult and simplified approaches to patients with leukocytosis, leukopenia, erythrocytosis and thrombocytopenia. 

Join our mailing list and receive a PDF copy of our show notes every Monday. Rate us on iTunes, recommend a guest or topic and give feedback at thecurbsiders@gmail.com.

Credits

Written, Produced and Edited by: Matthew Watto MD, FACP

Cover Art and Infographic by: Matthew Watto MD, FACP

Hosts: Stuart Brigham MD; Matthew Watto MD, FACP; Paul Williams MD, FACP

Guest: Mary Kwok MD

Sign Up for a course w/our Chief of POCUS, Dr. Renee Dversdal!

American College of Physicians

Point-of-Care Ultrasound: Foundational Skills for Internists

November 7-8, 2019 and November 9-10, 2019 (same 2-day course repeated back to back)

Crowne Plaza O’Hare Hotel and Conference Center, Rosemont, IL

Registration is now open at acponline.org/pocus

Point-of-Care Ultrasound: Foundational Skills for Internists

April 21-22, 2020 (during Internal Medicine Meeting 2020)

Los Angeles Convention Center

Registration will open at the end of September

Point-of-Care Ultrasound: Advanced Skills for Outpatient Practice

April 22, 2020 (during Internal Medicine Meeting 2020)

Los Angeles Convention Center

Registration will open at the end of September

AIUM

A special thanks to our Chief of POCUS Dr. Renee Dversdal and the AIUM for hosting The Curbsiders at another fantastic AIUM Point of Care Ultrasound (POCUS) Conference in Portland, Oregon at OHSU, July 2019. Check out https://aium.org for upcoming events. Next year’s IM POCUS course will be July 2020 in Portland! Dates are still TBD. Stay tuned.

TRUST^TM (Train the Ultrasound Trainers)

Are you looking to boost your skills teaching POCUS? Well, Our Chief of POCUS in collaboration with Kashlak West & Zedu Ultrasound Training Solutions created a course just for people like you. Sign up here: https://www.ultrasoundtraining.com.au/courses/category/train-the-ultrasound-trainer-trust

Time Stamps

• 00:00 Intro; Paul shame’s the audience; Guest bio
• 03:17 Guest one-liner, book recommendation* –Emperor of All Maladies (book) by Siddhartha Mukherjee, When Breath Becomes Air (book) by Paul Kalanithi; Career advice -set goals for whatever you’re learning.
• 08:43 Picks of the week: John Wick 3 (film); The Movies That Made Me (podcast) by Joe Dante; The Tim Ferriss Podcast with Julie Rice of Soul Cycle; Infinity Chamber (film) by Travis Milloy
• 11:50 A case of asymptomatic leukocytosis; Red flags; Repeat the CBC until it’s normal
• 17:30 The peripheral smear; Leukemoid reaction
• 20:00 The physical exam; When to send flow cytometry?
• 22:18 A case of lymphopenia; benign ethnic neutropenia; What to look for in the history
• 27:10 A case of erythrocytosis; Checking EPO levels; JAK2 mutation; Differential Diagnosis; Therapeutic Phlebotomy; Physical findings of Polycythemia Vera
• 36:53 A case of thrombocytopenia; Lab workup; Differential diagnosis; Pathophysiology; Culprit meds
• 45:35 Advice for internists
• 46:36 Take Home Points
• 47:46 Dr. Kwok’s disclaimer
• 48:10 Outro and post credit scene

Take Home Points – Common CBC Abnormalities

Dr. Kwok’s Take Home Points

1. Dr. Kwok’s plea to internists. Please repeat the CBC before referring patients to a hematologist. 
2. Do a really good history and physical exam to help narrow the differential diagnosis
3. Note if the patient has an isolated cytopenia or multiple cell lines down. The latter case suggests a primary bone marrow process.
4. Send an EPO level for erythrocytosis to differentiate myeloproliferative neoplasm (low EPO) from secondary erythrocytosis (high EPO) due to cardiopulmonary disease, smoking, renal disease or EPO producing tumor

Show Notes – Common CBC Abnormalities

Initial Approach to common CBC abnormalities

Look at the white count (WBC), Hemoglobin (Hgb), Platelets (Plt), MCV, and the differential (diff). 

Next, calculate the absolute counts e.g. absolute neutrophil count, etc. The absolute counts trump the percentages when reviewing a CBC with diff.

The William’s Rule

Keep repeating labs until they become normal. Dr. Kwok agrees that an abnormal CBC should be repeated to see if the abnormalities persist.

Leukocytosis

DDx for leukocytosis

Smoking and infections commonly cause neutrophilia. Lymphocytosis is suspicious for a lymphoproliferative disorder. Older patients with monocytosis may have CMML. 

Smoking is a common cause of neutrophilia. Tell the patient to stop smoking and then repeat the labs.

Leukocytosis Red Flags

Blasts, elevated basophils (suggests myeloproliferative neoplasm), absolute eosinophil count over 1500, absolute lymphocyte count over 5000 all warrant a hematology consult. These patients may need bone marrow biopsy.

Check a peripheral smear. 

Are the cells mature or immature? Which type of cell predominates? Hematopathologists are often willing to review abnormal findings.

What is flow cytometry?

Blood is tagged with markers. Millions of cells are analyzed and plotted on a scatter plot. Then, a pathologist identifies any abnormal populations of cells e.g. clonal B cells, T cells, myeloid blasts, or lymphoid blasts.

When should flow cytometry be ordered? 

• Patient with suspicious lymphadenopathy
• Patient with absolute lymphocyte count over 5000 

Leukopenia 

Initial steps

Review previous CBCs to check for chronicity. Review medication exposures to look for culprits. Ask about a history of acute, chronic or recurrent infections. Does the patient have a known rheumatologic disorder?

Check the peripheral smear to look for blasts or other abnormal cells. 

Benign ethnic neutropenia

Benign ethnic neutropenia can be confirmed by checking an RBC phenotype. Patients who are Duffy null (negative for Duffy A and B) likely have benign ethnic neutropenia. 

Rheumatologic diseases may be a cause of neutropenia, but they’re usually symptomatic (NOT an occult process).

Erythrocytosis (aka Polycythemia)

Defined as hemoglobin (Hgb) above 16.5 g/dL for a man, or above 16 g/dL for a woman (Tefferi A. UpToDate 2019).

DDx for erythrocytosis (polycythemia)

• Myeloproliferative neoplasm (MPN) such as polycythemia vera (PV)
• Renal disease – Cysts, renal artery stenosis, renal cell carcinoma
• Chronic hypoxemia from lung disease, sleep apnea, smoking
• Certain erythropoietin (EPO) producing tumors

Workup erythrocytosis

Check for splenomegaly. Repeat the CBC. Next, check an EPO level. A low EPO level suggests a primary process live PV. Consider sending a JAK2 mutation for patients with a low EPO level and clinical suspicion for PV. A normal or elevated EPO level suggests a secondary erythrocytosis from hypoxia, a renal process or EPO secreting tumor. 

Polycythemia Vera signs and symptoms

Aquagenic pruritus is stinging, burning or itching that occurs in response to water exposure. Erythromelalgia is intermittent burning pain (often severe) in hands or lower extremities. It’s believed to be caused by blocked blood vessels.

The case of Coach

Coach was Stuart’s patient with low testosterone, obstructive sleep apnea and elevated Hgb from secondary erythrocytosis. He requested testosterone replacement therapy. The patient was noncompliant with CPAP at baseline, but improved his efforts to try and drop his Hgb. He eventually was given testosterone replacement therapy, but his Hgb shot up to nearly 20 g/dL and he had to stop it again.

Polycythemia Anecdote #1

Dr. Kwok hasn’t seen much of a drop in Hgb for her patients on CPAP for sleep apnea. 

Polycythemia Anecdote #2

Dr. Watto had a single patient like Coach who wanted testosterone therapy, but had severe secondary polycythemia. A local hematologist conducted regular therapeutic phlebotomy to keep the patient’s Hgb at a safe level while receiving testosterone replacement. Note: the patient had a high Hgb despite compliance with his CPAP and smoking cessation. 

Thrombocytopenia

Simplified approach to thrombocytopenia

• Is the thrombocytopenia isolated or accompanied by anemia and/or leukopenia? 
• Review the patient’s medication list and pay attention to any recent changes or exposures (e.g. antibiotics, chemo, antidepressants). 
• Is there evidence of hemolysis?
• Consider DIC, TTP/HUS, HIT or acute leukemia in patients who look sick. 
• Ask about hepatitis C, HIV and if dyspepsia is present, H. pylori infection. 
• Decide if the patient is at risk for nutritional deficiencies. Do they have known liver disease (hypersplenism from portal hypertension or decreased production of thrombopoietin), thyroid disease, autoimmune or rheumatologic conditions?

Thrombocytopenia Anecdote

Dr. Kwok has not seen platelets improve much after treating patients for H. pylori.

Isolated thrombocytopenia

First repeat the CBC. Next, check a peripheral smear. Use a blue top tube to overcome any platelet clumping noted on the smear. 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)

Immune thrombocytopenia (ITP) is a diagnosis of exclusion.

Goals

Listeners will identify common abnormalities found in the complete blood count, perform appropriate follow up testing if needed and recognize who needs referral to hematology.

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. 

Links*

1. Emperor of All Maladies (book) by Siddhartha Mukherjee, 
2. When Breath Becomes Air (book) by Paul Kalanithi
3. John Wick 3 (film)
4. The Movies That Made Me (podcast) by Joe Dante
5. The Tim Ferriss Podcast with Julie Rice of Soul Cycle
6. Infinity Chamber (film) by Travis Milloy

*The Curbsiders participates in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising commissions by linking to Amazon. Simply put, if you click on my Amazon.com links and buy something we earn a (very) small commission, yet you don’t pay any extra.

References

1. Tefferi A et al. How to Interpret and Pursue an Abnormal Complete Blood Cell Count in Adults. Mayo Clinic Proc. 2005
2. Lambert MP et al. Review Clinical updates in adult immune thrombocytopenia. Blood. 2017
3. Rodeghiero F et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children/report from an international working group. Blood. 2009

Disclosures

Dr Kwok reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures. 

Citation

Kwok M, Brigham SK, Williams PN, Watto MF. “#167 LIVE! Common CBC Abnormalities with Mary Kwok MD”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/podcast. August 26, 2019.