White Blood Cell Disorders

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Author(s): John Levine, M.D., 2009 License:Unless otherwise noted, this material is made available under the terms of the Creative Commons Attribution 3.0 License: http://creativecommons.org/licenses/by/3.0/ We have reviewed this material in accordance with U.S. Copyright Law and have tried to maximize your ability to use, share, and adapt it. The citation key on the following slide provides information about how you may share and adapt this material. Copyright holders of content included in this material should contact open.michigan@umich.edu with any questions, corrections, or clarification regarding the use of content. For more information about how to cite these materials visit http://open.umich.edu/education/about/terms-of-use. Any medical information in this material is intended to inform and educate and is not a tool for self-diagnosis or a replacement for medical evaluation, advice, diagnosis or treatment by a healthcare professional. Please speak to your physician if you have questions about your medical condition. Viewer discretion is advised: Some medical content is graphic and may not be suitable for all viewers.

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Myeloid Cell DisordersM2 Hematology/Oncology Sequence John Levine, MDWinter 2009

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Myeloid Cell Disorders: Goals Define members of the myeloid series Understand: white blood cell maturation the white blood cell count and differential ‘philias’ and ‘penias’ of the myeloid series members and associated clinical settings recruitment of WBC from the circulation. Associate white blood cell defects with function*

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Maturation of Myeloid CellsGM-CSFG-CSF*

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Mature Myeloid CellsNeutrophilEosinophilBasophilMonocyte*

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Assessment of Circulating WBCThe total white blood cell count (WBC) and differential are measured in an automated counter WBC reflects the circulating pool of myeloid and lymphoid cells WBC in each microliter (ml;mm3) is reported Relative proportion of each type of WBC is indicated by a percentage Absolute number is the percentage of each type of WBC multiplied by the total WBC*

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White Blood Cell Counts: Normal Ranges*J. Levine

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White Blood Cell Counts: Disease States*J. Levine

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Neutrophil Maturation25%65%8%2%ProliferationMaturationIntravascular6-7 days6-7 days12 hTissues 12hBone Marrow*J. Levine

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Neutrophil Maturation - Proliferative PhaseMyeloblastPromyelocyteMyelocyte25 %Proliferation*Source Undetermined (All Slides)J. Levine

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65 % of myeloid cellsMaturation 6-7 daysNeutrophil - Maturation PhaseMetamyelocyteBandNeutrophil*J. LevineSource Undetermined (All Slides)

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8%2%12 hTissues 12hIntravascularApproximately 10% of the developing neutrophils are in the circulation, marginated or in the tissue. CirculatingMarginatingFate of the mature neutrophil*

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Disorders of Neutrophil Numbers*J. Levine

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Definition of Neutrophilia - too manyNormal ANC is 1500-7700/ml Neutrophilia: abnormally high ANC Shift to the left: ↑’d release of precursors from the bone marrow not necessarily associated with neutrophilia*

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NeutrophiliaChronic Stimulation Excess cytokine stimulates proliferative pool Causes: Infection Down's Syndrome Pregnancy/Eclampsia Chemotherapy recovery Myeloproliferative disorders Marrow metastases Acute shift from marginating to circulating pool ↑ measured WBC, not total WBC Causes: Steroid treatment Exercise Epinephrine Hypoxia Seizures Other stress*

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Example: exercise induced neutrophilia*Source Undetermined

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Neutropenia: too fewNeutropenia Definition: ANC < 1500/µl ANC 500-1000 increased risk of infection from exposure ANC < 500: increased risk of infection from host organisms African-Americans: lower normal neutrophil counts (1000-1200)*

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Acquired Causes of Neutropenia*

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Increased DestructionAnti-neutrophil antibodyNeutrophil-Antibody ComplexUptake and destruction of neutrophil by the RE system*J. Levine

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Shift to Marginating PoolCirculatingMarginatingCirculatingMarginatingSevere infection / Endotoxin release Hemodialysis Cardiopulmonary bypass*J. Levine

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Evaluation of NeutropeniaIf visit prompted by a fever and ANC is low, treat promptly for infection Suspect medication: major cause of neutropenia If no culprits, bone marrow exam for: Malignancy Infiltration by non-marrow cells Arrest of cell growth Myeloproliferative disorder*

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Cyclic Neutropenia21 day cycle autosomal dominant fever, mouth ulcers Treatment G-CSF usually improves after puberty *Source Undetermined

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Congenital NeutropeniaMaturation arrest frequent infections, often serious mouth sores may lose teeth or develop severe gum infections Increased risk of leukemia Tx: G-CSF, BMT*Source Undetermined

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Role of NeutrophilResponds to chemotactic factors released from damaged tissue Rolls and attaches to the endothelial cell wall protein and carbohydrate interactions (selectins and their ligands). Becomes activated by chemotactic factors Tightly adheres through the integrin family of proteins. Migrates across the endothelial cell wall. Phagocytizes organisms so that they are contained within a vesicle or phagosome. Releases granule products and reduced oxygen species (e.g. hydrogen peroxide and superoxide) to kill organisms*

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Function of the Circulating NeutrophilAttachment/rollingActivationAdhesionMigrationPhagocytosis*J. Levine

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Last Updated: 8th March 2018

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