Left Shift Indices in Blood Cell Count - Clinical Significance

Introduction

Blood is a vital body fluid that carries oxygen and essential nutrients to all parts of the body. It is continuously circulating in the body with the help of the cardiovascular system (heart and blood vessels). The blood in circulation is also called peripheral blood. Though blood exists in a fluid state, it is not entirely made of liquids. Blood is a colloidal solution that contains various types of cells suspended in it. The fluid part of blood is plasma, and the cellular components of blood are red blood cells (RBCs), white blood cells (WBCs), and platelets.

These cellular components perform specific functions such as oxygen transport (RBCs), protecting against infections (WBCs), and preventing bleeding (platelets). During infections, organ dysfunctions, or disease conditions like cancers, the normal functions of these cellular components are affected and result in their abnormalities. The changes in cellular components of the blood are detected by several blood tests and help in the identification of underlying disorders.

What Is Blood Cell Count?

Blood cell count refers to complete blood count (CBC), which analyses and provides details about the cellular components of the blood.

• It is an estimated measure of the total number of erythrocytes (RBCs), leukocytes (WBCs), and thrombocytes (platelets) in the circulating blood.

• Changes due to different disease conditions affect the blood components. Therefore a total blood cell count helps in diagnosing and monitoring many disorders.

• Due to the accessibility of initial clues and progressive information, a complete blood cell count is considered one of the most important medical laboratory investigations.

• This test is an essential diagnostic tool that helps to study the cause, symptoms, treatment outcome (prognosis), and prevention of several diseases.

• Blood cell count is performed by both automated techniques (cell analyzer) as well as manual methods (peripheral blood smear examination).

• From blood cell count, the changes in the functioning of the bone marrow (site of production and maturation of blood cells) are also assessed.

What Is Meant by a Left Shift in Blood Cell Count?

The red blood cells, platelets, and majority of the white blood cells (neutrophils, eosinophils, basophils, monocytes) are produced from the bone marrow. The process of producing various types of blood cells is called hematopoiesis. The bone marrow comprises hematopoietic stem cells (cells that produce cellular components of blood). These hematopoietic stem cells differentiate into various lineages for different types of blood cells. From each lineage, specific groups of cells such as RBCs, WBCs, and platelets develop.

The cells that undergo differentiation from the hematopoietic stem cells to generate new blood cells are called precursors (cells from which another cell of the same kind is formed). All the maturation and development of blood cells occur within the bone marrow, and only matured blood cells (RBCs, WBCs, and platelets) are released in the blood circulation. Thus only mature blood cells are present in peripheral blood. The presence of immature cells or precursors in peripheral circulation indicates altered disease pathologies.

The left shift, also called blood shift, represents the abnormal increase and presence of immature cellular blood components and their precursors in the peripheral blood, predominantly neutrophils (a type of white cell). In occasional cases, the left shift also refers to the presence of immature erythrocytes and reticulocytes in the peripheral circulation.

What Is the Clinical Significance of the Left Shift?

Some of the disease conditions or toxicities lead to changes in the bone marrow, and it is reflected in blood composition. These changes are detected by the left shift in blood cell count. Some of the significant features of the left shift are as follows -

• Neutrophil left shift is frequently seen during infections. It is valuable in monitoring the course of infections and their prognosis.

• Erythroid left shift (in RBCs) is rarely seen in severe anemic conditions.

• The left shift Indices of both myeloid (WBCs) and erythroid (RBCs) cells help in identifying toxicities and acute blood changes.

• They also help in the diagnosis of neoplastic changes like myeloid leukemia.

• The presence of nucleated blood cells and precursors indicates stressed bone marrow activity in conditions like severe hypoxia (unavailability of oxygen to the tissues).

• It also occurs after the administration of certain drugs that affect the immune system.

When Does the Left Shift Occur?

The left shift is observed in diverse clinical conditions. Sometimes, circulating nucleated red blood cell precursors (erythroblasts) is seen along with increased circulating precursors of neutrophils. Such a phenomenon is termed a leucoerythroblastic left shift. Some of the disorders that enhance the left shift are as follows -

• Bacterial infection.

• Hemorrhage.

• Anoxia.

• Metabolic acidosis.

• Postoperative conditions.

• Parenteral corticosteroid administration.

• Administration of immunomodulators like granulocyte colony-stimulating factor (G-CSF).

• Hypoxia.

• Severe anemia (hemolytic and hemorrhagic).

• Severe sepsis.

• In marrow infiltrations such as leukemia, myeloma, lymphoma, and secondary metastasis).

• In extramedullary hematopoiesis (production of blood cells outside the bone marrow).

• Bone marrow fibrosis.

• Myeloid hyperplasia.

• Dysplastic myeloid leukemia.

• Severe endotoxemia.

• Excessive bone marrow injury.

What Is Neutrophil Left Shift?

Neutrophils are the first immune cells (WBCs) that are activated as the host response to infectious microorganisms. These neutrophils rapidly move to the sites of bacterial infection, induce inflammatory mediators and kill the bacteria. A mature neutrophil contains a segmented nucleus (two to five lobes). Whereas, in its precursors, the nucleus is unsegmented and appears as a band often termed band neutrophils.

Degenerative Neutrophil Left Shift

• A degenerative left shift is seen in severe acute inflammation due to bacterial infection.

• Here, the numbers of band neutrophils are increased more than mature neutrophils.

• Usually, the neutrophil count remains normal or low (neutropenia).

• Neutrophils (both mature and immature) show toxic changes and accelerated maturation.

• Because the existing neutrophils are exhausted, and there is an increased demand for neutrophils, immature neutrophils are mobilized from the bone marrow storage sites.

Regenerative Neutrophil Left Shift

• It is usually seen in myeloid hyperplastic conditions, where the bone marrow produces excessive neutrophils due to inflammatory stimuli.

• Neutrophilia (increased neutrophil count) is seen in a regenerative left shift where mature neutrophils are more than immature neutrophils.

• Neutrophils show no or mild toxic changes depending on the severity of inflammation.

• This shift occurs in response to the release of the cytokine that is stimulated by neoplasms like lymphoma.

What Are the Diagnostic Benefits of Left-Shift Indices?

Various clinical factors are associated with left-shift indices and are useful for evaluating the progressive course of related underlying disorders. Some of their diagnostic benefits are as follows -

• The standardized left shift value for absolute band neutrophil count is greater than 700/microL.

• A left shift helps in identifying hematopoietic neoplasms such as myeloid leukemia, where abnormal hematopoietic cells are detected in the peripheral smear.

• The presence of reticulocytes (RBC precursors) in peripheral blood film indicates severe hypoxic stress on the bone marrow, forcing them to release prematurely, as in the case of severe hemolytic anemias.

• Left shifts assessed at different time periods help to evaluate the prognostic course of bacterial infections and their treatment outcome.

• Severe neutrophilia with a left shift occurs in leukemoid reactions.

• Toxic granulations are seen in severe infections where the cytoplasm of neutrophils contains increased microbicidal granules.

Conclusion

Left shift is observed in several clinical conditions that affect cellular components of blood. It signifies abnormal production of various forms of blood cells and is indicative of hematological pathologies. The understanding of left shift indices has specific diagnostic importance and its clinical application is effectively used in predictive, diagnostic, and prognostic procedures.