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What's a "Normal" WBC?

April 25, 2024

My experience on the other side of the stethoscope and the world as a patient in Cameroon, West Africa.

May 2024

Elna Saah, MD, MSElna Saah, MD, MS, is a pediatric hematologist at Children’s Healthcare of Atlanta’s Aflac Cancer and Blood Disorders Center and an assistant professor of pediatrics at Emory University.

At the 2023 ASH Annual Meeting, Maureen Achebe, MD, MPH, moderated a Spotlight Session titled “What Is a ‘Normal’ Neutrophil Count? The Duffy Red Cell Antigen, Ancestry, Genetics and Evolution,” which followed a Blood Advances paper on the topic that was published earlier in the year.1,2 Two panelists — Lauren Merz, MD, MSc, and John Mark Sloan, MD — discussed the evolution, distribution, prevalence, and need to implement Duffy-null–specific ranges, providing an overview of the expected neutrophil count in people with the Fy(a-b-) phenotype and suggesting potential changes to avoid pathologizing healthy individuals. I recalled this presentation during an encounter of my own not too long ago in which my white blood cell count (WBC) was questioned.

On a recent trip to my childhood town of Limbe (formerly called Victoria), in my birth country of Cameroon, West Africa (yes, we were part of the British Commonwealth), I was thrust on the other side of the stethoscope thanks to a relatively severe bout of food poisoning. I arrived via the Douala International Airport and made it to Limbe, where I had a late-night meal consisting of broasted fish. Limbe is a small, little-known town that sits on the rocky volcanic Atlantic coastline against a backdrop of the active volcano Mt. Cameroon. A small river and its tributary run through Limbe and drain into the Atlantic via an estuary. The town is quaint and bustling with life, and the coastline is dotted with restaurants, bars, and fresh fish markets. The fish market sells freshly broasted fish, other seafood, and tropical fare like plantains.

My symptoms began about 12 hours after consuming the fish, “fresh” caught from the ocean. Within two hours of the onset of severe diarrhea and vomiting, I could feel myself getting dehydrated and failed at attempts of oral rehydration. Sensing I was getting into trouble, I contacted a family friend, a practicing orthopedic surgeon, who directed me to the nearby community medical center. This center dealt with the COVID-19 pandemic; they became proficient in managing diarrheal diseases and dehydration, unfortunately, after the AIDS epidemic (also known as “slims disease”) and also handle intermittent (and, regrettably, not infrequent) cholera outbreaks.

Upon arrival, I was ushered into the intake room. The setting was rudimentary but efficient, devoid of technological interference (electronic health records and beeping monitors were conspicuously absent). IV access was obtained promptly by a competent nurse, and another venipuncture was administered for lab draws only (complete blood count [CBC] and comprehensive metabolic panel [CMP]). The matron observed while the young on-call doctor took a pen-and-paper history and physical.

The doctor returned within 30 minutes of the first (of three) 500 mL lactated ringers (LR) to discuss my CBC results. “Your WBC count is high,” she reported, and with knee-jerk hematologist reflexes, I questioned what high was. Well, 9.3 K/mm3 was the value, and a series of thoughts and questions followed, including “What is your normal range?” Most patients are between 4 and 6 K/mm3.

Before I could cite the emerging literature and the call for the establishment of reference ranges for Duffy-null associated neutrophil count, I was given a dose of ceftriaxone. The neutrophilia and left shift led to the conclusion that my episode of acute gastroenteritis was probably more bacterial in etiology than viral.

I was then transferred to a makeshift overnight unit for an ongoing oral challenge, a second dose of ceftriaxone 12 hours later, and monitoring. The night nurse came in to check vital signs twice, with a small portable tray that had cotton balls and rubbing alcohol to clean the tip of the reusable thermometer used to take axillary temperatures. Nothing fancy. My blood pressure was obtained manually and confirmed by palpation.

At discharge, I was presented with a detailed itemized bill for each test, medication, and IV fluids (three 500 mL bags of LR). Upon review of the labs, I noticed a urinalysis (UA) was not done. Three other investigations were done: CBC, CMP, and stool studies. The CMP would inform both the hydration status and acute kidney injury, rendering a UA noncritical at the time.

I learned a few lessons from this experience:

  • Rudimentary care is less at risk of being fragmented and can be just as good.
  • The workforce in Cameroon was older, and personnel spent more time in their roles, resulting in minimal turnover.
  • When patients have out-of-pocket costs, cost-effective care is a default. The costs of care are subsidized by the government (and in this case, the church missionaries who established and support the center). However, there are still considerable out-of-pocket costs, which are exorbitant for the locals. The caregivers are mindful of this, though, and practice cost-effective medicine at its best. No noncritical labs were performed, and after the critical dehydration period was over and I could tolerate an oral challenge, I was not continued on maintenance IV fluids overnight. Instead, I was provided with a 1.5-liter bottle of purified water with oral rehydration solution and encouraged to drink all night.
  • Finally, what is “normal” is determined by the means of the populations sampled. While this is a lesson that has been ingrained in us from our introductory statistics definitions of mean, mode, and median, it is a reminder that our environments and perspectives skew our reality.

As the annual meeting session highlighted, it is well established that people of African and Middle Eastern extraction, particularly Yemeni, have lower absolute neutrophil counts (ANC) than white individuals. We perform many a consult for this in our hematology clinics, with some patients being worked up unnecessarily. This lower ANC has been termed benign ethnic or genetic neutropenia because the patients are clinically not more susceptible to bacterial infections. During times of infection, they mount an appropriate demargination response. We now know that the reduced circulating ANC is seen in people who are homozygous for the Duffy-null phenotype, Fy(a-b-).

As we work through the development and implementation of a Duffy-null–specific ANC reference range, it may behoove us to obtain values from cross sections of these populations. The second part of redefining these normal ranges, as emphasized in Dr. Sloan’s presentation, is to avoid pathologizing this subpopulation and recognize the impact these variances may have on our clinical care in cancer and research more broadly.

Elna Saah, MD, MS
Associate Editor

References

  1. Achebe MO. What is a “normal” neutrophil count? The Duffy red cell antigen, ancestry, genetics and evolution. Presented at the 65th American Society of Hematology Annual Meeting and Exposition; December 11, 2023; San Diego, California.
  2. Merz LE, Story CM, Osei MA, et al. Absolute neutrophil count by Duffy status among healthy Black and African American adults. Blood Adv. 2023;7(3):317-320.

The content of the Editor’s Corner is the opinion of the author and does not represent the official position of the American Society of Hematology unless so stated.

Have a comment about this editorial? Let us know what you think; we welcome your feedback. Email the editor your response, along with your full name and professional affiliation if you’d like us to consider publishing it, at ACNEditor@hematology.org.

 

 

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