WBC 4.0 - 10.9 HIGH

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The abnormality chosen is:

LEUKOCYTOSIS, a white blood cell count greater than 12,000 cells/microL. Common conditions associated with this abnormality include infections, malignancies, allergic reactions, leukemoid reaction, stress-induced demargination, and the ingestion of exogenous steroids. Leukemoid reactions refer to an excessive response of the bone marrow when stimulated by infection, trauma, or other stresses. Leukoerythroblastosis refers to the presence of immature leukocytes and nucleated erythrocytes in the peripheral blood, and this condition may occur without leukocytosis. The differential diagnosis of leukocytosis is dependent on which cell line is elevated.

NEUTROPHILIA is a commonly encountered clinical abnormality. Usually, the neutrophil count is tightly regulated. Fluctuations are noted in women which correspond to their menstrual cycle. Physiologic causes of neutrophilia include stress (this causes demargination of neutrophils from their storage pool), physical exercise, and pregnancy. Non-pathologic neutrophilia may also be seen in chronic cigarette smokers. Chronic idiopathic neutrophilia is a term used to describe a disorder in which certain individuals have a chronically elevated neutrophil count without any underlying pathology. Common pathologic causes of neutrophilia include infections, inflammation, tissue destruction, or malignancy. Neutrophilia is also associated with myeloproliferative diseases, hemorrhage, hemolysis, diabetic ketoacidosis, thyroid storm, eclampsia, and medications including lithium chloride, epinephrine, or steroids. Neutrophilia secondary to infection is associated with bandemia, referred to as a left shift, and the presence of toxic granulations, Dohle bodies, and/or cytoplasmic vacuoles. Leukemoid reaction is an excessive left shift that manifests as an elevated neutrophil count and an abundance of neutrophil precursors. This reaction is usually secondary to infections or malignancies Leukemoid reaction must be differentiated from chronic myelogenous leukemia (CML). This is done by checking the leukocyte alkaline phosphatase (LAP) level and for the presence of the Philadelphia chromosome. In CML, LAP is lacking and usually, the Philadelphia chromosome is present along with significant leukocytosis. A leukemoid reaction is different in that the LAP is elevated and the Philadelphia chromosome is absent in the presence of a significant leukocytosis.

LYMPHOCYTOSIS may be absolute (increased WBC with increased lymphocyte percentage) or relative (normal WBC with an increased percentage of lymphocytes). Lymphocytosis is associated with infection especially viral, infectious mononucleosis or pertussis. An atypical lymphocytosis is often seen with EBV infectious mononucleosis. Once the above infections are excluded, the remaining considerations in adults include chronic lymphocytic leukemia, thyrotoxicosis, adrenal insufficiency and large granular lymphocyte leukemia (diagnosed by lymphocyte immunophenotyping by flow cytometry and T-cell receptor gene rearrangement studies on a peripheral blood sample).

EOSINOHPILIA is defined as an absolute eosinophil count greater than 500 cells. Secondary eosinophila is associated with allergic reactions, Addisons disease, asthma, connective tissue diseases, drug reactions, certain parasitic infections, and the pulmonary eosinophilias (Churg-Strauss syndrome). Parasitic infections associated with eosinophilia include amebiasis, ascariasis, schistosomiasis, strongyloidiasis, and trichinosis. When there is concomitant fever, rash, and renal abnormalities, acute interstitial nephritis should be included in the differential diagnosis although this symptom complex is also seen with Chrug-Strauss syndrome. The work-up may include a CXR, urinalysis, sputum and/or stool (1 sample 20% sensitivity and 3 samples 50%) studies for ova and parasites, cortisol level, ESR, ANA, rheumatoid factor, anti-cyclic citrullinated peptide, and HIV antibodies. If parasitic infection is highly suspected, further work-up should include serologic studies for strongyloidiasis, filariasis, schistosomiasis, trichinellosis, and viseral larva migrans (Toxocara canis or T cati). If an underlying secondary cause is not suspected then possible etiologies include: esoinophilia associated with myeloid or lymphoid neoplasms with PDGFR or FGR1 mutations; clonal eosinophilia of a WHO-defined myeloid malignancy; chronic eosinophilic leukemia-not otherwise specified (CEL-NOS); lymphocytic variant hypereosinophilia; or idiopathic eosinophilia which includes hypereosinophilic syndrome (HES). The presence of circulating blasts, dysplastic cells, monocytosis, or an elevated serum tryptase level indicate the need for fluorescence in situ hybridization (FISH) or reverse transcription polymerase chain reaction (RT-PCR) on a peripheral blood sample. If the FIP1L1-PDGFRA mutation is present then a diagnosis of associated myeloid neoplasm may be made and imatinib mesylate therapy should be started. If these tests are not diagnostic or if further information is needed prior to treatment then bone marrow biopsy is necessary looking for 5q33, 4q12, or 8p11.2 translocations which would indicate PDGFRB, PDGFRA, or FGFR1 clonal eosinophilia, respectively Bone marrow examination is also helpful to diagnose or exclude systemic mastocytosis (elevated tryptase level, aggregates of abnormal mast cells, mast cell expression of CD25, or the presence of KITD816V mutation), chronic myelomonocytic leukemia and chronic eosinophilic leukemia, not otherwise specified (CEL-NOS). If these conditions have been excluded then a diagnosis of idiopathic eosinophilia (no end organ damage) or HES (presence of end organ damage) remains. End organ damage is characterized by cardiomyopathy, pneumonitis, dermatitis, sinusitis, CNS involvement, peripheral neuropathy, gastrointestinal, or thrombotic complications. Further testing in these patients should include a chest radiograph, ECHO, and serum troponin level, plus further evaluation dictated by symptoms (PFT's, gastrointestinal endoscopy, skin biopsy, coronal sinus CT scanning, or neuroimaging). Patients with HES should undergo further testing for peripheral blood lymphocyte phenotyping and T-cell receptor gene rearrangement studies in order to exclude the diagnosis of lymphocytic variant hypereosinophilia.  HES may be treated with prednisone (1mg/kg/day for 2-3 weeks followed by a slow taper over 3 months). HES patients who fail to respond to oral prednisone may be treated with imatinib mesylate, mepolizumab, or alemtuzumab. Close surveillance is adequate in cases of idiopathic eosinophilia. 

BASOPHILIA is an uncommon disorder. Its presence is often indicative of certain myeloproliferative disorders such as chronic myelogenous leukemia (CML), polycythemia vera (PCV), or myelofibrosis.

MONOCYTOSIS is associated with underlying infections, immunologic diseases, or a chronic inflammatory process. Monocytosis may occur after chemotherapy or drug-induced neutropenia and should resolve in time. Persistent unexplained monocytosis may be an indicator of a myeloproliferative disorder and may require bone marrow examination and cytogenetic studies.