Low White Blood Cell Count And Low Lymphocytes – Per L) in non-pregnant adults, is a relatively common finding with a wide differential. It is important for clinicians to be able to distinguish malignant from nonmalignant etiologies, and to distinguish between the most common nonmalignant causes of leukocytosis.

Per L) is sometimes referred to as a leukemoid reaction. This level of elevation can occur in some serious infections, such as Clostridium difficile infection, sepsis, organ rejection, or in patients with solid tumors.

Low White Blood Cell Count And Low Lymphocytes

Per L) after 12 hours of life (95% confidence interval). By two weeks of age this decreases to about 5,000 to 20,000 per mm

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There is also a shift from relative lymphocyte to neutrophil predominance from early childhood through adolescence and adulthood.

During pregnancy there is a gradual increase in the normal WBC count (third trimester 95% upper limit = 13,200 per mm

Per L) after cesarean deliveries. Notably, positive bacterial cultures are not associated with leukocytosis or neutrophilia, making leukocytosis an unreliable discriminator for deciding which postpartum patients require antibiotic therapy.

The life cycle of leukocytes includes development and differentiation, storage in the bone marrow, margination within the vascular spaces, and migration into tissues. Stem cells in the bone marrow produce cell lines of erythroblasts, which become red blood cells; megakaryoblasts, which become platelets; lymphoblasts; and myeloblasts. Lymphoblasts develop into various types of T- and B-cell lymphocytes. Myeloblasts further differentiate into monocytes and granulocytes, a designation that includes neutrophils, basophils, and eosinophils (Figure 1). Once WBCs mature within the bone marrow, 80% to 90% remain stored in the bone marrow. This large reserve allows for a rapid increase in the circulating WBC count within hours. A relatively small pool (2% to 3%) of leukocytes circulates freely in the peripheral blood

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; the rest remains deposited along the edges of blood vessel walls or in the spleen. Leukocytes spend most of their lifespan in storage. Once a leukocyte is released into circulation and peripheral tissue, its lifespan varies from two to 16 days, depending on the type of cell.

Although the differential of the major types of WBCs is important in evaluating the cause of leukocytosis, it is sometimes helpful to think in terms of absolute, rather than relative, leukopenias and leukocytosis. To calculate the absolute cell count, the total leukocyte count is multiplied by the differential percentage. For example, with a normal WBC count of 10,000 per mm

Per L) and an elevated monocyte percentage of 12, the absolute monocyte count is 12% or 0.12 times the WBC count of 10,000 per mm

The most common type of leukocytosis is neutrophilia (an increase in the absolute number of mature neutrophils to more than 7,000 per mm)

White Blood Cell

Per L]), which can arise as a result of infections, stressful conditions, chronic inflammation, medication use and other causes (Table 3).

Lymphocytosis (when lymphocytes make up more than 40% of the WBC count or the absolute count is greater than 4,500 per mm

Per L]) may occur in patients with pertussis, syphilis, viral infections, hypersensitivity reactions and certain subtypes of leukemia or lymphoma. Lymphocytosis is more likely to be benign in children than in adults.

Epstein-Barr virus infection, tuberculosis or fungal disease, autoimmune disease, splenectomy, protozoal or rickettsial infections, and malignancy can cause monocytosis (monocytes make up more than 8% of the WBC count or the absolute count is greater than 880 per mm

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Per L]), although uncommon, may suggest allergic conditions such as asthma, urticaria, atopic dermatitis or eosinophilic esophagitis, drug reactions, dermatological conditions, malignant diseases, connective tissue disease, idiopathic hypereosinophilic syndrome or parasitic infections, including helminths (tissue parasites more). as gut-lumen parasites).

Per L]) is rare and unlikely to cause leukocytosis in isolation, but may occur with allergic or inflammatory conditions and chronic myelogenous leukemia

Per L), can result from a variety of etiologies. Any source of stress can cause a catecholamine-induced demargination of WBCs, as well as increased release from the bone marrow storage pool. Examples include surgery, exercise, trauma, burns and emotional stress.

Medications known to increase the WBC count include corticosteroids, lithium, colony-stimulating factors, beta agonists, and epinephrine. During the recovery phase after bleeding or hemolysis, a rebound leukocytosis may occur.

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Leukocytosis is one of the hallmarks of infection. In the acute stage of many bacterial infections, there are mainly mature and immature neutrophils (Figure 2); sometimes, as the infection progresses, there is a shift to lymphocyte predominance. The release of less mature bands and metamyelocytes into the peripheral circulation leads to the so-called “left shift” in the WBC differential. Of note, some bacterial infections paradoxically cause neutropenias, such as typhoid fever, rickettsial infections, brucellosis and dengue.

Viral infections can cause leukocytosis early in their course, but a sustained leukocytosis is not typical, except for the lymphocytosis in some childhood viral infections.

An elevated WBC count is a suggestive, but not definitive, marker of the presence of significant infection. For example, the sensitivity and specificity of an elevated WBC count in the diagnosis of acute appendicitis are 62% and 75%, respectively.

For the diagnosis of severe bacterial infections without a source in children with fever, the discriminatory value of leukocytosis is less than that of other biomarkers, such as C-reactive protein or procalcitonin.

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Per L) is one of the criteria for the systemic inflammatory response syndrome (or sepsis when there is a known infection), leukocytosis alone is a poor predictor of bacteremia and not an indication for obtaining blood cultures.

Other acquired causes of leukocytosis include functional asplenia (mainly lymphocytosis), smoking and obesity. Patients with a chronic inflammatory condition, such as rheumatoid arthritis, inflammatory bowel disease, or a granulomatous disease, may also exhibit leukocytosis. Genetic causes include hereditary or chronic idiopathic neutrophilia and Down syndrome.

Leukocytosis may herald a malignant disorder, such as an acute or chronic leukemia (Figure 3), or a myeloproliferative disorder, such as polycythemia vera, myelofibrosis, or essential thrombocytosis. A previous article on leukemia in American Family Physician reviewed the characteristics and differentiation of malignant hematopoietic disorders.

Many solid tumors can lead to a leukocytosis in the leukemoid range, either through bone marrow involvement or production of granulocyte colony-stimulating or granulocyte-macrophage colony-stimulating factors.

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(Figure 4). Chronic leukemias are most often diagnosed after incidental findings of leukocytosis on complete blood counts in asymptomatic patients. Patients with features suggestive of hematologic malignancies require prompt referral to a hematologist/oncologist (Table 5).

A systematic approach to patients with leukocytosis includes identifying historical clues that suggest possible causes (Figure 5). Fever and pain may accompany infections or malignancies; other constitutional symptoms, such as fatigue, night sweats, weight loss, easy bruising or bleeding, may suggest malignancy.

Previous diagnoses or concomitant conditions causing chronic inflammation should be noted, as well as recent stressful events, medication use, smoking status, and history of splenectomy or sickle cell anemia. A history of an elevated WBC count is important because duration will help determine the likely cause. Leukocytosis that lasts hours to days has a different differential diagnosis (eg, infections, acute leukemias, stress reactions) than a case that persists for weeks to months (eg, chronic inflammation, some malignancies).

The physical examination should note erythema, swelling or lung findings suggestive of an infection; murmur suggestive of infective endocarditis; lymphadenopathy suggestive of a lymphoproliferative disorder; or splenomegaly suggestive of chronic myelogenous leukemia or a myeloproliferative disorder; petechiae or ecchymosis; or painful, inflamed joints that indicate connective tissue disease or infection.

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Initial laboratory evaluation should include a repeat complete blood count to confirm the elevated WBC level, with differential cell counts, and a review of a peripheral blood smear. The peripheral smear should be examined for toxic granulations (indicating inflammation), platelet clumps (which can be misinterpreted as WBCs), the presence of immature cells, and uniformity of the WBCs. When evaluating a leukocytosis with lymphocyte predominance, a monomorphic population is concerned with chronic lymphocytic leukemia, while a pleomorphic (different sizes and shapes) lymphocytosis indicates a reactive process.

With all forms of leukocytosis, concurrent abnormalities in other cell counts (erythrocytes or platelets) suggest a primary bone marrow process and should prompt hematology/oncology evaluation.

As indicated by the history and examination findings, physicians should consider performing cultures of blood, urine, and joint or body fluid aspirations; rheumatology studies; a test for heterophile antibodies (mononucleosis spot test); and serological titers. Radiologic studies may include chest radiography (to identify infections, some malignancies, and some granulomatous diseases) and, as indicated by the history, computed tomography or bone scan. If hematologic malignancy is suspected, additional confirmatory tests may include flow cytometry, cytogenetic testing, or molecular testing of the bone marrow or peripheral blood.

Data sources: The primary literature search was completed using Essential Evidence Plus and included searches of the Cochrane, POEM and NICE guideline databases using the search term leukocytosis. Additionally, PubMed searches were performed using the terms leukocytosis and white blood cell. Search dates: 31 October and 17 December 2014 and September 2015.

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The authors thank Melissa King, MD, Department of Hematology/Oncology, Eglin Air Force Base Hospital, for reviewing the manuscript, and Niquanna Perez, Eglin Air Force Base laboratory services, for obtaining peripheral smear images.

The opinions expressed in this article are those of the authors and do not reflect the official policy or position of the US government, the Department of Defense, or the US Air Force.

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