Evaluation of neutrophilia

Histologic findings supporting an infectious or inflammatory condition: toxic granulations, Dohle bodies, and cytoplasmic vacuoles. Evidence of these changes to neutrophil morphology are highly sensitive (80%), although not specific (58%), for an existing inflammatory or infectious condition.[29]Seebach JD, Morant R, Ruegg R, et al. The diagnostic value of the neutrophil left shift in predicting inflammatory and infectious disease. Am J Clin Pathol. 1997 May;107(5):582-91. https://academic.oup.com/ajcp/article/107/5/582/1757155 http://www.ncbi.nlm.nih.gov/pubmed/9128272?tool=bestpractice.com

If an inflammatory or infectious cause is suspected, elevated CRP, although a low-sensitivity test, should be determined. CRP >1 mg/dL has sensitivity of 79% for infection or inflammation.[29]Seebach JD, Morant R, Ruegg R, et al. The diagnostic value of the neutrophil left shift in predicting inflammatory and infectious disease. Am J Clin Pathol. 1997 May;107(5):582-91. https://academic.oup.com/ajcp/article/107/5/582/1757155 http://www.ncbi.nlm.nih.gov/pubmed/9128272?tool=bestpractice.com ​ Elevated total leukocyte count, increased ratio of neutrophils within total leukocyte count, and elevated CRP have 100% sensitivity for an inflammatory or infectious condition. However, positive predictive value of the combination is poor at 37%.[29]Seebach JD, Morant R, Ruegg R, et al. The diagnostic value of the neutrophil left shift in predicting inflammatory and infectious disease. Am J Clin Pathol. 1997 May;107(5):582-91. https://academic.oup.com/ajcp/article/107/5/582/1757155 http://www.ncbi.nlm.nih.gov/pubmed/9128272?tool=bestpractice.com

Can be measured to support an inflammatory or infectious cause for neutrophilia.

If clinically indicated.

If clinically indicated.

Total neutrophil count ≥8000/microliter has sensitivity of 60% and specificity of 58% for an infectious or inflammatory condition.[29]Seebach JD, Morant R, Ruegg R, et al. The diagnostic value of the neutrophil left shift in predicting inflammatory and infectious disease. Am J Clin Pathol. 1997 May;107(5):582-91. https://academic.oup.com/ajcp/article/107/5/582/1757155 http://www.ncbi.nlm.nih.gov/pubmed/9128272?tool=bestpractice.com ​ Presence of a neutrophilia typically predicts poor prognosis.

Histologic findings supporting an infectious or inflammatory condition: toxic granulations, Dohle bodies, and cytoplasmic vacuoles. Evidence of these changes to neutrophil morphology are highly sensitive (80%), although not specific (58%), for an existing inflammatory condition.[29]Seebach JD, Morant R, Ruegg R, et al. The diagnostic value of the neutrophil left shift in predicting inflammatory and infectious disease. Am J Clin Pathol. 1997 May;107(5):582-91. https://academic.oup.com/ajcp/article/107/5/582/1757155 http://www.ncbi.nlm.nih.gov/pubmed/9128272?tool=bestpractice.com

If an inflammatory or infectious cause is suspected, elevated CRP, although a low-sensitivity test, should be determined. CRP >1 mg/dL has sensitivity of 79% for infection or inflammation.[29]Seebach JD, Morant R, Ruegg R, et al. The diagnostic value of the neutrophil left shift in predicting inflammatory and infectious disease. Am J Clin Pathol. 1997 May;107(5):582-91. https://academic.oup.com/ajcp/article/107/5/582/1757155 http://www.ncbi.nlm.nih.gov/pubmed/9128272?tool=bestpractice.com ​ Elevated total leukocyte count, increased ratio of neutrophils within total leukocyte count, and elevated CRP have 100% sensitivity for an inflammatory or infectious condition. However, positive predictive value of the combination is poor at 37%.[29]Seebach JD, Morant R, Ruegg R, et al. The diagnostic value of the neutrophil left shift in predicting inflammatory and infectious disease. Am J Clin Pathol. 1997 May;107(5):582-91. https://academic.oup.com/ajcp/article/107/5/582/1757155 http://www.ncbi.nlm.nih.gov/pubmed/9128272?tool=bestpractice.com

Can be measured to support an inflammatory or infectious cause for neutrophilia.

Cytogenetic testing and relevant assessment by fluorescence in situ hybridization or polymerase chain reaction should be performed concurrently with diagnostic bone marrow aspiration and biopsy.

Cytogenetic testing and relevant assessment by fluorescence in situ hybridization or polymerase chain reaction should be performed concurrently with diagnostic bone marrow aspiration and biopsy.

Also decreased in polycythemia vera.

JAK2 V617F, CALR, and MPL mutations may occur in other myeloproliferative neoplasms (polycythemia vera, primary myelofibrosis) and myeloid malignancies.

Cytogenetic testing and relevant assessment by fluorescence in situ hybridization or polymerase chain reaction should be performed concurrently with diagnostic bone marrow aspiration and biopsy.

Also decreased in essential thrombocythemia.

Positive in most polycythemia vera patients. However, it is not specific and is found in other myeloproliferative neoplasms (essential thrombocythemia, primary myelofibrosis), chronic myelomonocytic leukemia, and acute myeloid leukemia.

Cytogenetic testing and relevant assessment by fluorescence in situ hybridization or polymerase chain reaction should be performed concurrently with diagnostic bone marrow aspiration and biopsy.

Presence of JAK2 V617F, CALR, or MPL mutation indicates a myeloproliferative neoplasm, but these mutations are not specific for primary myelofibrosis.[31]Tefferi A. Primary myelofibrosis: 2021 update on diagnosis, risk-stratification and management. Am J Hematol. 2021 Jan;96(1):145-62. https://onlinelibrary.wiley.com/doi/10.1002/ajh.26050 http://www.ncbi.nlm.nih.gov/pubmed/33197049?tool=bestpractice.com [32]McLornan DP, Godfrey AL, Green A, et al. Diagnosis and evaluation of prognosis of myelofibrosis: a British Society for haematology guideline. Br J Haematol. 2024 Jan;204(1):127-35. https://onlinelibrary.wiley.com/doi/10.1111/bjh.19164 http://www.ncbi.nlm.nih.gov/pubmed/37932932?tool=bestpractice.com

If peripheral blood sample contains thrombus resulting in platelet clumping, automated cell counters may mistake platelet clumps for white blood cells. Overall effect is a modest increase in WBC count, typically reported with associated thrombocytopenia.

If sample anticoagulation is adequate, spurious neutrophilia and thrombocytopenia may occur if patient has ethylenediaminetetraacetic acid (EDTA)-dependent agglutinins. Also known as pseudoleukocytosis and occurs in 0.1% of patients.[30]Savage RA. Pseudoleukocytosis due to EDTA-induced platelet clumping. Am J Clin Pathol. 1984 Mar;81(3):317-22. http://www.ncbi.nlm.nih.gov/pubmed/6422738?tool=bestpractice.com ​ Requires reassessment of platelet and total leukocyte counts in a non-EDTA blood collection tube.

Sample should be evaluated after warming to at least body temperature.

If peripheral blood sample is cooled below room temperature and contains cold-insoluble plasma proteins, a temperature-dependent increase in WBC and platelet counts occurs at ≤30°C. Precipitated cryoglobulin particles return to solution if sample is warmed to body temperature. Mean cell hemoglobin may also be elevated, which corrects with warming.

Anemia may be due to microangiopathic hemolytic anemias. Diagnosis is suggested by microangiopathic changes to red blood cells (fragmented red blood cells, reticulocytosis), and enlarged platelets.

Depending on the state of red blood cell production and cause of the anemia, reticulocyte count may be increased or decreased.

Neutrophilia may be present with or without solid tumor infiltration within bone marrow.

Evidence of primary hematologic malignancy should prompt additional testing, including flow cytometry, cytogenetics, and molecular studies.

After spleen resection, a moderate degree of neutrophilia is transient, but most patients continue to have chronically mild neutrophilia.

Cytogenetic testing and relevant assessment by fluorescence in situ hybridization or polymerase chain reaction should be performed concurrently with diagnostic bone marrow aspiration and biopsy.

Chronic neutrophilic leukemia is associated with activating mutations of the CSF3R gene, most commonly T618I.

Only a few patients present with neutrophilia. Types of myelodysplasia that may present with neutrophilia: chronic myelomonocytic leukemia, atypical chronic myeloid leukemia, and unclassifiable myelodysplastic/myeloproliferative neoplasm.

Cytogenetic testing and relevant assessment by fluorescence in situ hybridization or polymerase chain reaction should be performed concurrently with diagnostic bone marrow aspiration and biopsy.

Vitamin B12 deficiency should be ruled out.

Folate deficiency should be ruled out.

The 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumors no longer requires a blast count threshold for the diagnosis of AML with defining genetic abnormalities (except for BCR::ABL1 fusion and CEBPA mutation which require ≥20% blasts for diagnosis).[8]Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours: myeloid and histiocytic/dendritic Neoplasms. Leukemia. 2022 Jul;36(7):1703-19. https://pmc.ncbi.nlm.nih.gov/articles/PMC9252913 http://www.ncbi.nlm.nih.gov/pubmed/35732831?tool=bestpractice.com ​ In the International Consensus Classification, however, a blast count of ≥10% is required for diagnosing AML with defining genetic abnormalities (except for BCR::ABL1 fusion where a blast count of ≥20% is required).[9]Arber DA, Orazi A, Hasserjian RP, et al. International consensus classification of myeloid neoplasms and acute leukemias: integrating morphologic, clinical, and genomic data. Blood. 2022 Sep 15;140(11):1200-28. https://pmc.ncbi.nlm.nih.gov/articles/PMC9479031 http://www.ncbi.nlm.nih.gov/pubmed/35767897?tool=bestpractice.com

The 5th edition of the WHO Classification of Haematolymphoid Tumors no longer requires a blast count threshold for the diagnosis of AML with defining genetic abnormalities (except for BCR::ABL1 fusion and CEBPA mutation which require ≥20% blasts for diagnosis).[8]Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours: myeloid and histiocytic/dendritic Neoplasms. Leukemia. 2022 Jul;36(7):1703-19. https://pmc.ncbi.nlm.nih.gov/articles/PMC9252913 http://www.ncbi.nlm.nih.gov/pubmed/35732831?tool=bestpractice.com ​ In the International Consensus Classification, however, a blast count of ≥10% is required for diagnosing AML with defining genetic abnormalities (except for BCR::ABL1 fusion where a blast count of ≥20% is required).[9]Arber DA, Orazi A, Hasserjian RP, et al. International consensus classification of myeloid neoplasms and acute leukemias: integrating morphologic, clinical, and genomic data. Blood. 2022 Sep 15;140(11):1200-28. https://pmc.ncbi.nlm.nih.gov/articles/PMC9479031 http://www.ncbi.nlm.nih.gov/pubmed/35767897?tool=bestpractice.com

Cytogenetic testing and relevant assessment by fluorescence in situ hybridization or polymerase chain reaction should be performed concurrently with diagnostic bone marrow aspiration and biopsy.

Neutrophils appear to have 2 lobes with a single connecting strand. Pelgeroid (pseudo-Pelger-Huet) cells outside of the inherited disorder are also seen in myelodysplastic syndrome, and less commonly, in active infection, acute and chronic leukemia, or with medications such as mycophenolate mofetil, colchicines, and sulfonamides. These drugs cause pelgeroid features in the neutrophil nuclei, and neutrophils retain their cytoplasmic granulation.

Infants and children with Down syndrome may have temporary leukemoid reactions of unclear significance in the setting of stress or inflammation.

As neutrophils in this condition lack CD18, no leukocyte and beta-2 integrins remain.

Congenital asplenia has been identified in a subset of patients with chronic idiopathic neutrophilia.

Among patients presenting with suspected myocardial infarction, those with a total leukocyte count >9000/microliter were 4.5 times more likely to have confirmed myocardial infarction than patients with a total leukocyte count <6000/microliter.[24]Zalokar JB, Richard JL, Claude JR. Leukocyte count, smoking, and myocardial infarction. N Engl J Med. 1981 Feb 19;304(8):465-8. http://www.ncbi.nlm.nih.gov/pubmed/7453772?tool=bestpractice.com