Leukocytosis

Lindee Abe, APRN

A 58-year-old patient presents to the emergency department for several months of fatigue, night sweats, and decreased appetite. The patient is afebrile and has several bruises noted on their arms and legs. Laboratory testing is complete, and the patient’s white blood cell (WBC) count is 110,000/μL. How do you manage this patient?

Leukocytosis, or an elevated WBC count, is a laboratory finding that is often seen in the acute care setting. This is defined as a WBC count > 11,000 /μL. Leukocytosis is commonly associated with an infectious process; however, it is a nonspecific finding that various factors, including infection, inflammation, stress, medications, malignancy, and smoking, can cause. When leukocytosis is noted in a patient, the patient should be evaluated to determine if there is an underlying infectious process that is likely causing the leukocytosis.

Review the Differential

If leukocytosis is noted on a patient’s lab work, the provider should review the differential. The differential is typically included in the CBC (make sure to order the CBC with differential) and helps differentiate the types of WBCs present. This can allow the provider better to understand the potential underlying causes of the leukocytosis.

Neutrophils

Neutrophils are the largest group of WBCs on the differential and can be increased with bacterial infections, inflammation, stress, and corticosteroid use.

Lymphocytes

Lymphocytes are the next largest category of WBCs and can be increased in viral infections and leukemias (e.g., chronic lymphocytic leukemia). Infections and inflammation also cause elevated monocytes.

Eosinophils

Eosinophil elevation is typically associated with parasitic infections and allergic responses.

Basophils

Basophils are the smallest group of WBC, and an elevation always requires evaluation. An allergic reaction can cause elevated basophils, but may be due to cancer.

Bands

Bands are immature neutrophils, and elevations are also referred to as a “left shift,” which can indicate a bacterial infection or hematologic malignancy. After reviewing the different types of cells on the differential, I have compiled some helpful notes from practice that I have learned along the way. Bandemia warrants further investigation. It can indicate a significant infection or be the result of a hematologic malignancy. Specifically, this should trigger a sepsis workup if the patient presentation indicates sepsis (e.g., fever, tachycardia), including blood cultures, serum lactate, procalcitonin, blood gas analysis, imaging, and urinalysis.

While bandemia should always be explored, it does not always automatically mean the patient should be admitted. The patient may have a mild elevation, but be well-appearing and hemodynamically stable. An example would be a patient who recently completed a course of corticosteroids and has 11% bands on the differential with normal vital signs and no chronic medical conditions.

Bandemia can also indicate hematologic malignancy, such as leukemia. If a patient has a bandemia with an unexplained significantly elevated WBC count, leukemia should be ruled out. Years ago, in laboratory school, I was taught that bands were bad. While that is still true, the evaluation of a left shift is more nuanced than that.

Causes of Mild Leukocytosis

I have learned in practice that there are causes of mild leukocytosis that don’t need further evaluation. Smoking and pregnancy are two examples. However, while these conditions can cause an elevated WBC count, it is helpful to compare the elevation with previous WBC counts if available. An example would be a patient who is pregnant and has a WBC count of 13,000 μL. While this could be a normal variant with pregnancy, a review of the patient’s record shows the patient had a CBC the day before and a WBC count of 7,500 μL at that time. This indicates an elevation that requires further evaluation, as there has been a significant increase over a short period.

If there is concern for hematologic malignancy based on the CBC and differential, the provider should also review other hematology labs to provide a more comprehensive picture.

Anemia

Anemia (i.e., low hemoglobin) and thrombocytopenia (i.e., low platelet count) can also be found in leukemias due to crowding in the bone marrow, resulting in decreased red blood cell (RBC) production. The bone marrow crowding in leukemia can also cause thrombocytopenia. This can be tied back to the initial patient who presented with symptoms of anemia (i.e., fatigue) and thrombocytopenia (i.e., bruising easily). A peripheral smear can also show large numbers of immature cells and monomorphic lymphocytosis.

When to Hospitalize your Patient

While admissions are always nuanced and based on the complete clinical picture, there are situations where the patient should always be admitted. A patient with a WBC count greater than 100,000 μL should always be admitted. The severity of leukocytosis does not always indicate a hematologic malignancy, but it is a red flag for malignancy. In patients with a WBC count greater than 100,000 μL, this is associated with a poorer prognosis (e.g., tumor lysis syndrome) and requires emergent evaluation and workup. The patient initially met this criterion and should be admitted. Patients with a WBC count between 25,000 μL and 50,000 μL are generally due to an infection and should usually be admitted for treatment of the underlying disease. Patients with a WBC count between 50,000 μL and 100,000 μL should be admitted, as there is concern for a significant infection versus leukemia.

What is “Normal”

Anotherl key point that I have learned from practice is that a normal WBC count does not necessarily rule out an infectious etiology. Early on in the infectious process, the WBC can be normal. That is why it is crucial to consider the entire clinical picture when evaluating a patient. An elevated WBC count does not always equal infection. As discussed earlier, there are many other causes of elevated WBC count, but these are also usually mild evaluations. A pregnant patient with a WBC count of 29,000 μL is unlikely to have this count solely due to pregnancy.

There was one additional topic regarding the WBC count and differential that I found interesting. I recently discussed with a colleague who works in the laboratory about the use of the monocyte distribution width (MDW) as an early indicator of sepsis. Monocytes change shape in the early stages of infection, resulting in a wider distribution (i.e., greater deviation from normal). There is also new literature that is showing that a low monocyte count is an indicator of a poorer prognosis in patients with sepsis. This would be interesting to follow as more literature is published and investigated, and whether this should be included in sepsis bundles. This may be a topic of a future post as more information becomes available.

Back to our patient…

Returning to the patient initially discussed at the start of this post, the patient should be admitted. The patient has signs and symptoms that support a likely hematologic malignancy. The WBC count greater than 100,000 μL also supports a diagnosis of a hematologic malignancy.

References:

Chung H, Lee JH, Jo YH, Hwang JE, Kim J. Circulating Monocyte Counts and its Impact on Outcomes in Patients With Severe Sepsis Including Septic Shock. Shock. 2019;51(4):423-429. doi:10.1097/SHK.0000000000001193

Kluckman M, Stern E, Reeves L. Hematologic Emergencies. In: Stone C, Humphries RL. eds. CURRENT Diagnosis & Treatment: Emergency Medicine, 8e. McGraw-Hill Education; 2017. https://accessmedicine.mhmedical.com/content.aspx?bookid=2172&sectionid=165067275

Liu S, Li Y, She F, Zhao X, Yao Y. Predictive value of immune cell counts and neutrophil-to- lymphocyte ratio for 28-day mortality in patients with sepsis caused by intra-abdominal infection. Burns Trauma. 2021;9:tkaa040. Published 2021 Mar 22. doi:10.1093/burnst/tkaa040

Riley, LK & Rupert J. Evaluation of Patients with Leukocytosis. Am Fam Physician. 2015;92(11):1004-1011. https://www.aafp.org/pubs/afp/issues/2015/1201/p1004.html

Smith RJ, Sarma D, Padkins MR, et al. Admission total leukocyte count as a predictor of mortality in cardiac intensive care unit patients. JACC Adv. 2024;3(1):100757. doi:10.1016/j.jacadv.2023.100757