Review of Terms

Reticulocyte index	= Retic x (Pt HCT/Norm HCT)	The Reticulocyte production index (RPI, also called a corrected reticulocyte count) is a calculated value used in the diagnosis of anemia. This calculation is necessary because the raw reticulocyte count is misleading in anemic patients. The problem arises because the reticulocyte count is not really a count but rather a percentage: it reports the number of reticulocytes as a percentage of the number of red blood cells. In anemia, the patient's red blood cells are depleted, creating an erroneously elevated reticulocyte count.
Reticulocyte	Reticulocytes are newly formed erythrocytes. When stained supravitally with new methylene blue, they contain a blue reticular (RNA) network. These cells appear as macrocytes with diffuse cytoplasmic basophilia (polychromasia) when stained with Wright stain (next image). The normal reticulocyte count: 0.5-2.5%.
Polychromatic Red Cell	Polychromatic red cells are somewhat larger than normal and have a faint bluish or grayish-pink color. The color is due to a small amount of RNA. Significantly higher percentage reflects increased production - same significance as reticulocyte
Normal red cell morphology	Note the relative uniformity of size (7-8 microns; approximately the same size as the nucleus of a small lymphocyte) and shape of the red cells and the normal hemoglobin content as evidenced by the central area occupying approximately 1/3 of the cell.
Target Cells	surface/volume ratio Significant numbers of target cells occur in three situations: (1) hepatobiliary disease (increased cholesterol accumulating in cell membrane); (2) hemoglobinopathies C, D, and E; (3) thalassemias
Hemoglobin C disease	Homozygous hemoglobin C disease. In this condition there are many target cells as well as spherocytes. The target cell in stained preparations is a cell with hemoglobin on the edge, a light area, and more hemoglobin in the center. With scanning electron microscopy it appears to be bell-shaped. Target cells may be seen in small numbers in any type of anemia, but are seen in greatest numbers in liver disease, thalassemia, and hemoglobinopathies. They also may be artifactual due to slight pH changes in the glass slide. If they are seen only one area on the slide they are probably not true target cells but represent artifacts.
Spherocytes	surface/volume ratio Because of their spherical shape, which is due at least in part to loss of membrane area, they are more susceptible to osmotic stress as measured by the osmotic fragility test.
Acanthocyte	(spurr cell) 5-10 spicules	Red cells with multiple irregularly distributed, thorn-like spicules often with drumstick ends. -Found in association with hereditary abetalipoprotenemia but also seen in severe liver disease, hepatorenal failure, anorexia nervosa and in chronic starvation. -A small number of acanthocytes may be found in forms of hemolytic anemia (especially post splenectomy).
Echinocyte	(Burr cell) 10-30 spicules evenly distributed	Reflect damage to the normal cell membrane by various lytics–eg, saponin, bile salts, ionic detergents, lecithin; slow drying; aged blood; rarely, echinocytes reflect disease–eg, uremia or pyruvate kinase deficiency.
Pynoknocytes
Schistocytes	· Schistocytes are fragmented red cells and are seen in a variety of shapes and sizes. Schistocytes are associated with: -Thrombotic thrombocytopenic purpura (TTP) -Disseminated intravascular coagulation (DIC) -Microangiopathic hemolytic anemia, -Uremia -Carcinoma
Elliptocytes
Tear Drop Cells	These poikilocytes are most numerous in myelofibrosis with myeloid metaplasia (MMM). They may occur in small numbers in nuclear or cytoplasmic maturation defects. In MMM the spleen is responsible for producing this shape change. Following splenectomy, tear‑drop cells disappear. Whether these cells are produced within the spleen result from some change induced during circulation.
Stomatocytes
Kleihauer Betke Technique	Acid elution method for detecting HbF in maternal circulation
Phagophagia	Abnormal urge to eat large quantities of ice due to iron deficiency.
Geophagia	Abnormal urge to eat sand/earth due to iron deficiency.
Kelley Paterson Syndrome	Esophageal Webs and Fe Deficiency
Imerslund Grasbeck Syndrome		· A familial syndrome characterized by juvenile pernicious anaemia caused by selective malabsorption of vitamin B12 caused by a defect in the vitamin B12/intrinsic factor receptor. · Both sexes affected; onset most commonly in second year of life. · Principal symptoms include fatigue; weakness; pallor, gastrointestinal disorders with diarrhoea and vomiting, glossitis, jaundice, heart murmur and proteinuria. Urinary tract abnormalities are frequent, e.g. double ureters. · Inheritance is autosomal recessive
Donath Landsteiner antibody	Diagnosis of paroxysmal cold haemoglobinuria. This rare disorder may occur in syphilis and after viral infections in children.	· Collection by laboratory staff into 2 plain tubes, one at 37°C and one at 4°C. · Supernatant serum examined for evidence of red cell lysis, comparing a tube incubated at 4°C then 37°C with a tube maintained at 37°C. · The Donath Landsteiner antibody is an IgG autoantibody that binds to red cells in the cold and fixes complement; lysis occurs when cells are warmed to 37°C.
Basophilic stippling of erythrocytes (BSE)	Represents the spontaneous aggregation of ribosomal RNA in the cytoplasm of erythrocytes. These aggregates stain are visible, with routine hematology stains. is seen in lead poisoning, thalassemias, and other anemias.
Howell-Jolly bodies	Spherical blue bodies (Wright Stain) within or on erythrocytes: nuclear (DNA) debris. Associated with hyposplenism and pernicious anemia.
Heinz body	· Fresh blood incubated with supravital stain and examined by microscopy for presence of stained inclusions close to the red cell membrane (Heinz bodies). · Investigation of haemolysis (when fragmented spherocytes seen on blood film) or with history of exposure to oxidant chemical or drug. · Heinz bodies are denatured globin, and represent the end-product of oxidative degradation of haemoglobin. · Heinz bodies may be detected post-splenectomy, with oxidative haemolysis (in normals, but particularly in patients with G-6-PD deficiency) and in patients with unstable haemoglobinopathies.
G6PD Deficiency	· Mild in black Africans · G6PD during acute hemolysis may be falsely high.
Megaloblastic Anemia	Megaloblastic anemias, whether due to vitamin B₁₂ deficiency or folic acid deficiency, present with almost identical morphologic blood and bone marrow changes. Anemia is normochromic and macrocytic - MCV sometimes reaching as high as 150 cubic microns (μ³). Presence of macro-ovalocytes is considered quite characteristic of megaloblastic anemia. The reticulocyte count is usually decreased despite marked anemia. The so-called right shift of neutrophils (hypersegmented - six or more lobes) typify megaloblastic anemia. Thrombocytopenia is also not uncommon. The bone marrow is hyper-cellular, reflecting predominately the megaloblastic hyperplasia. The megaloblastic changes are noted in all three lines, i.e. red cells, white cells, and platelet precursors within the marrow. Serum B₁₂ and/or folic acid levels and the red cell folate concentration are decreased. Serum lactic dehydrogenase concentration is high.
Microcytic Hypochromic Anemia	A microcytic, hypochromic anemia characterized by decreased hemoglobin, decreased hematocrit, and decreased red cell indices (MCV, MCH and MCHC) is the hallmark of iron deficiency anemia. A moderate degree of anisocytosis (variation in size), moderate to marked poikilocytosis (variation in shape) and significant elliptocytosis frequently accompany moderate and severe degrees of iron deficiency anemia. The leukocyte count is generally normal, whereas the platelet count is frequently increased. The reticulocyte count may be normal or slightly decreased - rarely if ever increased. The bone marrow is normoblastic and depleted of stainable iron. Additional features of diagnostic importance are low serum ferritin, low serum iron, and increased total iron binding capacity (TIBC).
Myeloblast	A myeloblast is a large cell, 12-20 microns in diameter, with a nucleus that takes up most of the cell. Nuclear chromatin is fine, with little condensation and fairly homogenous in appearance. Nucleoli may vary in number and are apt to be large. The scanty cytoplasm is blue without granules.
Promyelocyte	A promyelocyte may be the same size as the myeloblast or even larger. Unlike the myeloblast, the promyelocyte's cytoplasm contains large black or purple granules. Nucleoli may be present.
Myelocyte	The myelocyte is smaller than the myeloblast or the promyelocyte. Unlike the myeloblast and promyelocyte, the myelocyte's cytoplasm contains specific granules, i.e. brick-red (eosinophils), large, blue-black granules (basophils), and lilac granules (neutrophils). The nucleus still has a round or oval shape and no nucleoli are present. Myelocytes are not seen on a normal peripheral blood smear.
Metamyelocyte	Metamyelocytes (Juvenile) are smaller than the myelocytes. There is more marked clumping of the nuclear chromatin so that the nucleus becomes much denser, takes up less than half the cell volume, and is indented (kidney-shaped).
Band (stab)	The band (stab) is similar to the metamyelocyte but the band is smaller and has a horseshoe-shaped nucleus. The cytoplasm may contain fine lilac granules (neutrophilic), brick-red granules (eosinophilic) or large blue-black granules (basophilic). Bands normally account for 0-5% of the total leukocyte count in circulating blood of the adult.
Segmented Neutrophil	A segmented neutrophil (poly) is approximately 12-14 microns in diameter. This is the final stage of granulocytic development. Normal polys generally have two to five lobes. Hypersegmented polys, containing six or more lobes, are characteristically seen in megaloblastic anemias. Polys normally account for 45-75% of a normal differential in an adult.
Monocyte	A monocyte has blue-gray cytoplasm and a lobulated nucleus. It's distinguished from other leukocytes by the folding-over of the nuclear lobe (fetal-shaped). 4-11% in a normal blood differential.
Basophil	Basophils are present in small numbers (0-3%) in a normal blood smear. Dark coarse granules and indistinct nucleus are characteristic. The basophil is a source of histamine and involved with allergic and inflammatory/immune responses. Increased numbers are seen in myeloproliferative disorders, e.g. chronic myelogenous leukemia and polycythemia vera.
Eosinophil	Eosinophils are characterized by the presence of numerous large red-orange granules which will fill the cytoplasm and sometimes cover the nucleus. 0-8% in normal blood, increased in parasitic infections, asthma, hay fever, and many other diseases.
Hypersegmented neutrophil	Oil immersion view shows a hypersegmented neutrophil, which has at least six nuclear lobes (the normal neutrophil generally has 2-5 lobes), consistently seen in megaloblastic anemias. Oval macrocytes and distorted RBC's (poikilocytosis) may also be seen.
Normal small lymphocyte	Normal small lymphocyte with its pale blue cytoplasm and dense, dark-staining nucleus. Note: the size of the nucleus is approximately the same size of normal red blood cells (approximately 7 microns). 16-46% in a normal adult blood smear, increased in infectious mononucleosis, lymphocytic leukemia, and many other diseases
Basophilia	Amount of RNA in each cell: Represented by bluish hue in cytoplasm of RBC. Basophilia normally decreases with cell maturity
Supravital stain	Stain that colors cells while they're still alive; i.e., adding stain to blood, allowing time to stain, and then making smear. For example, new methylene blue as used for reticulocyte staining.
Anisocytosis	Varying sizes (diameter) of RBC on peripheral smear
Poikilocytosis	Varying shapes of RBC on peripheral smear
Anisochromia	Two cell populations circulating simultaneously. One population is microcytic and hypochromic, and the other is normocytic and normochromic. This occurs in three places only: (1) treated iron deficiency anemia; (2) post transfusion of a hypochromic patient with a normochromic donor; (3) sideroblastic anemia.
Hypochromia	Normal erythrocytes tend to have a central pale area that is less than 1/3 of the cell diameter. Hypochromia is present when the pale area is larger than this
Methemoglobinemia	Erythrocytes (RBCs) possess 4 hemoglobin chains, each of which contains a heme moiety. These hemoglobin chains function to transport and deliver oxygen to tissues. Methemoglobin can be found in RBCs when there is oxidation (ie, loss of an electron) of the iron moiety, changing the normal oxygen-carrying ferrous (Fe2+) state to the ferric (Fe3+) state. Ferric heme is incapable of binding oxygen because of a stoichiometric alteration of the molecule
Dohle Body	The arrow points to a Dohle body in a neutrophil. Dohle bodies are basophilic cytoplasm left over from the progranulocyte stage of development. They represent rapid turnover of cells and are seen together with toxic granulation.
Alder-Reilly Anomaly	This was observed in a child with gargoylism. The anomaly is characterized by prominent granules (similar to toxic granulation) in the cytoplasm of segmented neutrophils, lymphocytes and monocytes. The anomaly is found in mucopolysaccharide disorders.
Pelger-Huet anomaly	Congenital autosomal dominant disorder in which granulocyte nuclei fail to segment normally. In the homozygote state the nucleus is round. In heterozygotes most granulocytes have bilobed nuclei ("pince-nez" cells) resembling bands. The trait is benign and occurs in 1 in 6,000 people. Cell function is normal.
May-Hegglin anomaly	Rare autosomal dominant abnormality characterized by large pale basophilic inclusions resembling Dohle bodies and appear to be altered RNA. Giant platelets, and sometimes thrombocytopenia are associated with this. The anomaly is usually benign but may be associated with bleeding.
HAM test	HAM Test/ Acid Serum Test/ PNH Test/ Paroxysmal Noctural Hemoglobinuria test, Serum lysis	HAM test is used to evaluate patients with suspected PNH (Paroxysmal Noctural Hemoglobinuria) or suspected congential dyserythropoietic anemia, especially with hemosiderinuria, Pancytopenia, decreased RBC acetyl cholinesterase, decreased leukocyte alkaline phosphatase, negative direct Coomb’s test, and/or apparent marrow failure. Diagnosis of PNH shows that the suspected patient’s red cells have a high sensitivity to complement mediated hemolysis. Partial hemolysis occurs with hereditary erythroblastic multinuclearity disease. PNH is a disease of increased complement sensitivity of red ell membranes, granulocytes and platelet membrane. Positive test result shows lysis of Red cells in acidified serum samples with patients cell (not with normal cells). Flow cytometry is now the preferred method for PNH screening where a population of CD55 and / or CD59 cells is diagnostic of PNH Hams test is still indicated in the investigation of HEMPAS. Contact the laboratory.
Evans Syndrome		Evans syndrome is an uncommon condition defined by the combination (either simultaneously or sequentially) of immune thrombocytopenia (ITP) and autoimmune haemolytic anaemia (AIHA) with a positive direct antiglobulin test (DAT) in the absence of known underlying aetiology. This condition generally runs a chronic course and is characterised by frequent exacerbations and remissions. First-line therapy is usually corticosteroids and/or intravenous immunoglobulin, to which most patients respond; however, relapse is frequent. Options for second-line therapy include immunosuppressive drugs, especially ciclosporin or mycophenolate mofetil; vincristine; danazol or a combination of these agents. More recently a small number of patients have been treated with rituximab, which induces remission in the majority although such responses are often sustained for <12 months and the long-term effects in children are unclear. Splenectomy may also be considered although long-term remissions are less frequent than in uncomplicated ITP. For very severe and refractory cases stem cell transplantation (SCT) offers the only chance of long-term cure. The limited data available suggest that allogeneic SCT may be superior to autologous SCT but both carry risks of severe morbidity and of transplant-related mortality. Cure following reduced-intensity conditioning has now been reported and should be considered for younger patients in the context of controlled clinical trials.

Peripheral blood (red cell) abnormalities and their associated diseases.
Abnormality	Description	Associated diseases
Acanthocytosis	Small cells with thorny projections.	Abetalipoproteinemia.
Anisocytosis	Abnormal variation in size.	Any severe anemia.
Heinz Bodies	Small, round inclusions of denatured hemoglobin seen under phase microscopy or with supravital staining.	Congenital hemolytic anemias resulting in hemoglobin precipitates (e.g. glucose-6-phosphate dehydrogenase deficiency).
Nucleated Red Cell	Erythrocyte with a nucleus still present.	Marked marrow erythroid hyperplasia or marrow replacement (i.e. tumor cells).
Pappenheimer bodies	Siderotic granules, staining blue with Wright or Prussian blue stain.	Increased marrow iron, absent spleen, and some hemolytic anemias.
Poikilocytosis	Abnormal variation in shape.	Any severe anemia.
Rouleaux	Aggregated erythrocytes regularly stacked on one another.	Multiple myeloma, cold agglutinin disease, viral infections.
Schistocytes	Irregularly shaped cells or cell fragments (severe poikilocytosis).	Disseminated intravascular coagulation, microangiopathic hemolytic anemia, thrombotic thrombocytopenic purpura, and uremia.
Sickle Cells	Crescent-shaped cells.	Sickle cell hemoglobinopathies.
Spherocytosis	Spherical cells without pale centers; often small.	Hereditary spherocytosis, Coombs-positive hemolytic anemias.
Stomatocytosis	Red cells with slit-like, instead of circular, areas of central pallor.	Congenital hemolytic anemia, thalassemia, burns, lupus erythematosus, lead poisoning, and liver disease.
Target Cells	Cells with a dark center and periphery and clear ring in-between.	Thalassemia, liver disease, Hemoglobinopathies (S, C, SC, S-thalassemia).