Neutropenia

Neutropenia is seen with acute severe inflammatory processes where demand for neutrophils overwhelms supply, both in the peripheral blood and bone marrow. A left shift, or increased numbers of immature neutrophils, usually accompanies the neutropenia as the bone marrow storage pool is recruited to the site of inflammation. Normal or decreased numbers of mature neutrophils accompanied by equal or higher numbers of immature neutrophils (bands, metamyelocytes, myelocytes) is often referred to as a degenerative left shift, although variations exist in the definition of this term. This situation indicates acute, severe inflammation which has overwhelmed the ability of the bone marrow to meet the demand for mature neutrophils.

Canine parvoviral infection causes neutropenia in two ways– the virus causes enteritis and neutrophils are recruited into the damaged intestinal epithelium. The virus also infects rapidly dividing cells in the bone marrow, which is initially manifested as impaired production of neutrophils and monocytes. Close monitoring of the leukogram is often indicated with parvoviral infection as dramatic changes, which can aid in prognostication, often occur very quickly. Feline panleukopenia virus affects cats in a similar way and close monitoring of the CBC is equally useful with this disease.

Mild neutropenia without a left shift or toxic change is occasionally seen in healthy animals and presumably represents fluctuation of the normal neutrophil count. These animals have no clinical evidence of inflammatory disease, and no other changes on the CBC.

Persistent neutropenia, particularly if moderate to severe and with no left shift or toxic change, may be due to a bone marrow disorder and inadequate granulopoiesis. Causes include viruses or other infectious agents; drugs, chemicals, or antibodies that selectively target neutrophil precursors; bone marrow necrosis; occupation of the bone marrow cavity with neoplastic cells – hemopoietic or metastatic from nonhemopoietic tissues; fibroplasia of the bone marrow; or primary disorders of granulopoiesis or hemopoiesis. In addition to drugs which are known to potentially cause neutropenia, idiosyncratic reactions can occur in individual animals. These reactions could be immune-mediated due to binding of foreign/drug antigens to the surface of neutrophils or their precursors. The importance of obtaining a complete history including a thorough investigation of exposure to or administration of drugs, chemicals, or supplements, cannot be overemphasized.

Genetic disorders of neutrophil production are much less common than acquired neutropenia. The classical example of hereditary neutropenia in veterinary medicine is cyclic neutropenia, or more correctly, cyclic hemopoiesis, of Grey Collie dogs. This disorder affects erythropoiesis and thrombopoiesis as well as granulopoiesis and is a stem cell defect which results in cyclical decreases in neutrophil, erythrocyte and platelet numbers.

Bone marrow examination is usually indicated when unexplained persistent neutropenia occurs. Neutrophilic hypoplasia, with no other changes, suggests injury or interference with production at an early stage of granulopoiesis. If common causes are ruled out based on history and additional tests, the term idiopathic neutropenia may be used. A finding of neutrophilic hyperplasia on bone marrow examination together with neutropenia on the CBC suggests a maturation disorder, such as myelodysplasia, neoplasia of the neutrophil lineage, a disorder affecting release of neutrophils from the bone marrow, or early recovery from damage to the neutrophil lineage. When additional cell lines are affected, a more generalized marrow disorder or injury is suspected. Prognosis may be determined in these situations by monitoring the CBC over time in conjunction with repeated bone marrow evaluations.