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57 EXAMINATION OF BLOOD SMEARS AND BONE MARROW

57 EXAMINATION OF BLOOD SMEARS AND BONE MARROW
Harrison’s Manual of Medicine

57

EXAMINATION OF BLOOD SMEARS AND BONE MARROW

Blood Smears

Erythrocyte (RBC) Morphology

RBC Inclusions

Leukocyte Inclusions and Nuclear Contour Abnormalities

Platelet Abnormalities
Bone Marrow

Indications

Interpretation
Bibliography

BLOOD SMEARS
Erythrocyte (RBC) Morphology

Normal: 7.5-µm diameter.

Reticulocytes (Wright’s stain)—large, grayish-blue, admixed with pink (polychromasia).

Anisocytosis—variation in RBC size; large cells imply delay in erythroid precursor DNA synthesis caused by folate or B12 deficiency or drug effect; small cells imply a defect in hemoglobin synthesis caused by iron deficiency or abnormal hemoglobin genes.

Poikilocytosis—abnormal RBC shapes; the following are examples: Acanthocytes (spur cells)—irregularly spiculated; abetalipoproteinemia, severe liver disease, rarely anorexia nervosa. Echinocytes (burr cells)—regularly shaped, uniformly distributed spiny projections; uremia, RBC volume loss. Elliptocytes—elliptical; hereditary elliptocytosis. Schistocytes (schizocytes)—fragmented cells of varying sizes and shapes; microangiopathic or macroangiopathic hemolytic anemia. Sickled cells—elongated, crescentic; sickle cell anemias. Spherocytes—small hyperchromic cells lacking normal central pallor; hereditary spherocytosis, extravascular hemolysis as in autoimmune hemolytic anemia, (G6PD) deficiency. Target cells—central and outer rim staining with intervening ring of pallor; liver disease, thalassemia, hemoglobin C and sickle C diseases. Teardrop cells—myelofibrosis, other infiltrative processes of marrow (e.g., carcinoma). Rouleaux formation—alignment of RBCs in stacks; may be artifactual or due to paraproteinemia (e.g., multiple myeloma, macroglobulinemia).
RBC Inclusions

Howell-Jolly bodies—1-µm diameter basophilic cytoplasmic inclusion that represents a residual nuclear fragment, usually single; asplenic pts.

Basophilic stippling—multiple, punctate basophilic cytoplasmic inclusions composed of precipitated mitochondria and ribosomes; lead poisoning, thalassemia, myelofibrosis.

Pappenheimer (iron) bodies—iron-containing granules usually composed of mitochondria and ribosomes resemble basophilic stippling but also stain with Prussian blue; lead poisoning, other sideroblastic anemias.

Heinz bodies—spherical inclusions of precipitated hemoglobin seen only with supravital stains, such as crystal violet; G6PD deficiency (after oxidant stress such as infection, certain drugs), unstable hemoglobin variants.

Parasites—characteristic intracytoplasmic inclusions; malaria, babesiosis.
Leukocyte Inclusions and Nuclear Contour Abnormalities

Toxic granulations—dark cytoplasmic granules; bacterial infection.

Döhle bodies—1- to 2-µm blue, oval cytoplasmic inclusions; bacterial infection, Chédiak-Higashi anomaly.

Auer rods—eosinophilic, rodlike cytoplasmic inclusions; acute myeloid leukemia (some cases).

Hypersegmentation—neutrophil nuclei contain more than the usual 2–4 lobes; usually >5% have ³5 lobes or a single cell with 7 lobes is adequate to make the diagnosis; folate or B12 deficiency, drug effects.

Hyposegmentation—neutrophil nuclei contain fewer lobes than normal, either one or two: Pelger-Hüet anomaly, pseudo-Pelger-Hüet or acquired Pelger-Hüet anomaly in acute leukemia.
Platelet Abnormalities
Platelet clumping—an in vitro artifact—is often readily detectable on smear; can lead to falsely low platelet count by automated cell counters.
BONE MARROW
Aspiration assesses cell morphology. Biopsy assesses overall marrow architecture, including degree of cellularity. Biopsy should precede aspiration to avoid aspiration artifact in the specimen.
Indications
ASPIRATION   Hypoproliferative or unexplained anemia, leukopenia, or thrombocytopenia, suspected leukemia or myeloma or marrow defect, evaluation of iron stores, workup of some cases of fever of unknown origin.
Special Tests   Histochemical staining (leukemias), cytogenetic studies (leukemias, lymphomas), microbiology (bacterial, mycobacterial, fungal cultures), Prussian blue (iron) stain (assess iron stores, diagnosis of sideroblastic anemias).
BIOPSY   Performed in addition to aspiration for pancytopenia (aplastic anemia), metastatic tumor, granulomatous infection (e.g., mycobacteria, brucellosis, histoplasmosis), myelofibrosis, lipid storage disease (e.g., Gaucher’s, Niemann-Pick), any case with “dry tap” on aspiration; evaluation of marrow cellularity.
Special Tests   Histochemical staining (e.g., acid phosphatase for metastatic prostate carcinoma), immunoperoxidase staining (e.g., immunoglobulin or cell surface marker detection in multiple myeloma, leukemia, or lymphoma, lysozyme detection in monocytic leukemia), reticulin staining (increased in myelofibrosis), microbiologic staining (e.g., acid-fast staining for mycobacteria).
Interpretation
CELLULARITY   Decreases with age after age 65 years from about 50% to 25–30%.
ERYTHROID:GRANULOCYTIC (E:G) RATIO   Normally about 1:2, the E:G ratio is decreased in acute and chronic infection, leukemoid reactions (e.g., chronic inflammation, metastatic tumor), acute and chronic myeloid leukemia, myelodysplastic disorders (“preleukemia”), and pure red cell aplasia; increased in agranulocytosis, anemias with erythroid hyperplasia (megaloblastic, iron-deficiency, thalassemia, hemorrhage, hemolysis, sideroblastic), and erythrocytosis (excessive RBC production); normal in aplastic anemia (though marrow hypocellular), myelofibrosis (marrow hypocellular), multiple myeloma, lymphoma, anemia of chronic disease.
Bibliography

For a more detailed discussion, see Adamson JW, Longo DL: Anemia and Polycythemia, Chap. 61, p. 348; and Holland SM, Gallin JI: Disorders of Granulocytes and Monocytes, Chap. 64, p. 366, in HPIM-15.

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