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Here is a most amazing site - consider it a review of all morphology.
SERIOUS EYE TRAINING
(this is my contribution - Gayle)
Echinocyte/Burr/Crenated – equally spaced, short projections
Basophilic stippling – blue-black specks throughout cytoplasm
Polychromasia – blue/pink cytoplasm
Acanthocyte – few irregularly spaced spicules of varying length
Stomatocyte – slit-like area of central pallor
Spherocyte – small, round, dense cell with lack of central pallor (usually microcytic)
Schizocyte/Schistocyte – fragmented, irregular cells
Keratocyte/Helmet Cell – cell fragmented in shape of helmet
Elliptocyte/Ovalocyte – oval or elliptical-shaped cell
Drepanocyte/Sickle Cell – thin, elongated cell pointed at least at one end
Codocyte/Target – hypochromic with hemoglobin pigment in center of central pallor
Leptocyte – thin flat cell with hemoglobin at periphery (increased central pallor)
Dacryocyte/Tear Drop Cell – in shape of drop; one pointed extremity
Siderocyte – dark-blue granules on periphery of cell (composed of iron)
Howell-Jolly Body – dense, round, bluish-red granule within cell (composed of DNA)Cabot Rings – reddish ring or figure-eight strand (composed of remnants of nucleus)
Malaria Parasites – small ring with red chromatin dot within RBC with, gradually growing until it fills the cell
Hematology: Clinical Principles and Applications
, B. Rodak, G. Fritsma, K. Doig
Posted by Kristen Gibs
Powerpoint RBC Morphology and Associated Disease: (By Bindu Panapalli)
RBC+Morphology & Associated Disease.pptx
(Just for sake of easy use, I put Bindu’s fabulous powerpoint into a chart. I edited where I thought necessary. I take no credit for this as I used most of the information Bindu found, and then used the RBC Crib Sheet from Gayle and our book to make some edits).
Types of RBCs.docx
RBC Indices and Anemia Classification
The values for MCV, MCHC, and MCH are derived from the hemoglobin (Hgb), hematocrit (Hct) and red blood cell count (RBC) by mathematical calculations:
Mean Corpuscular Volume (MCV) = Hct(%)x10/RBC(million/cmm) fL
Mean Corpuscular Hemoglobin Concentration (MCHC) = Hgb(g/dL)/Hct(%) g/dL
Mean Corpuscular Hemoglobin (MCH) = Hgb(g/dL)/RBC(million/cmm) pg
MCV values reflect the size, and MCH and MCHC reflect the amount and concentration of hemoglobin (color), of individual cells. These RBC indices are useful in the differential diagnosis of types of anemia.
Anemias are classified on the basis of cell size (MCV) and cell color (MCHC) and (MCH).
MCV less than lower limit of normal : microcytic
MCV within normal range : normocytic
MCV greater than upper limit of normal : macrocytic
MCHC less than lower limit of normal : hypochromic
MCHC within normal range : normochromic
Normocytic, normochromic anemia
Iron deficiency (detected early)
Chronic illness (sepsis, tumor)
Acute blood loss
Aplastic anemia (chloramphenicol toxicosis)
Acquired hemolytic anemias (prosthetic cardiac valve)
Micrositic, hypochromic anemia
Iron Deficiency (detected late)
Micrositic, normochromic anemia
Renal disease (erythropoietin loss)
Macrocytic, normochromic anemia
Vitamin B12 or folic acid deficiency
Decreased ability of the red blood cells to provide adequate oxygen supplies to body tissues may be due to decreased number of red blood cells, decreased amount of substance in red blood cells which transports oxygen (hemoglobin), or decreased volume of red blood cells.
vitamin B12 deficiency
drug-induced immune hemolytic anemia
hemolytic anemia due to g6pd deficiency
idiopathic aplastic anemia
idiopathic autoimmune hemolytic anemia
immune hemolytic anemia
iron deficiency anemia
secondary aplastic anemia
sickle cell anemia
Reference Source: Adam.com Encyclopedia
I found the above to be confusing, the first 3 are causes but the others are anemias. I am wondering if someone can clarify-MJO
I thought I would add in normal RBC morphology for comparison’s sake
Largest approx 12 u.
Smaller than Pronormoblast approx 10 u.
Smaller and more dense than basophilic normoblast approx.9 u.
Even smaller and more dense than the polychromatic normoblast, approx.8 u.
smaller than Orthochromic Normoblast, without a nuclues approx 7 u.
Smallest of all, no nuclues less than 6 u.
Fine reticular chromitin, looks like mashed potatoes. Hard to pick out Chromitin and parachromitin
More dense than pronormoblast, chromitin more dense and parachromitin more noticable
Nucleus more condensed, With noticeable chromatin and parachromitin
Neuclues very condensed, eccentic and very dark, no chromitin or para chromitim noticable
Large cell size with large nucleus and small or thin cytoplasma
Smaller than the pronormoblast, with a more condensed neucleus and thicker cytoplasma
Smaller than the Basophilic with a condensed necueuls and larger cytoplasma
Blue cytoplasma, but mostly nucleusn that looks like dark mashed potatoes
Still deeply basophilic
Begning to get pinker in cast
larger and getting pinker
Pink to red with some Reticulum with proper staining
Red biconcave disk with 1/3 as a center palor
No hemo, No globin
starting to make hemo and globin
Active hem and globin production, enough hemglobin is forming so we can start to visulaize
Active hem and globin and more hemoglobin
Last of the hemoglobin production
Number of Divisions
< < < < 50 Hours > > > >
Capable of mitosis
Capable of mitosis
capable of mitosis
Requires a special stain in order to be able to differentiate from Erythrocyte
Clinical Importance of RBC Morphology
Since different types of abnormal red blood cells arise by different etiologic processes, disease diagnosis can often be made by interpretation of red blood cell pathology in conjunction with CBC data and other clinical and laboratory information. The following diagram (Fig. 5) shows the etiology of the more common abnormal red blood cells, and they are individually discussed below.
Classification of RBC Morphologic Abnormalities
Acanthocytes ("spur cells, spicule cells") are spheroid RBCs with a few large spiny (thorny) projections. There are usually 5-10 spicules per cell, which show irregular spacing and thickness. Acanthocytes must be differentiated from echinocytes, which have shorter and more regular spicules (see below). Occasional acanthocytes can be seen after splenectomy, in patients with alcoholic cirrhosis, and in hemolytic anemias caused by pyruvate kinase (PK) deficiency. microangiopathic hemolytic anemia, autoimmune hemolytic anemia, sideroblastic anemia, thalassemia, severe burns, renal disease, McLeod phenotype, or infantile pyknocytosis. The majority of erythrocytes form acanthocytosis in the rare disease abetalipoproteinemia. Therefor, serum lipid evaluation is recommended if large numbers of acanthocytes are seen in the absence of an obvious clinical cause.
True agglutination is irregular clumping and agglutination of red blood cells into grape-like clusters. True agglutination must be differentiated from the rouleaux formation (pseudoagglutination) seen in patients with paraproteins or marked hypergammaglobulinemia or fibrinogenemia, which produces more regularly spaced clusters of red blood cells adhering side-to-side ("coin stacks," see below). True red cell agglutination usually indicates the presence of a cold reactive anti-red blood cell antibody ("cold agglutinin") found in cold agglutinin syndrome or paroxysmal cold hemoglobinuria, although some warm-reactive autoantibodies with wide temperature specificity may produce similar agglutination. True agglutination and pseudoagglutination cannot always be differentiated by light microscopy, but the Coomb’s test, cold agglutinin titer, and serum/urine protein analysis can provide additional information.
Basophilic stippling is the occurrence of fine, medium, or coarse blue granules uniformly distributed throughout some red blood cells. Fine stippling may be associated with polychromatophilia, while coarse stippling usually indicates impaired erythropoiesis. Heavy metal poisoning (e.g. lead and arsenic), hemoglobinopathies, thalassemias, sideroblastic anemias, pyrimidine-5’-nucleotidase deficiency, and other diseases should be excluded when coarse basophilic stippling is found.
Bite cells (degmacytes) are RBCs with peripheral single or multiple arcuate defects ("bites"). They are usually accompanied by at least a few blister cells (RBCs with vacuoles or markedly thin areas at periphery of membrane), acanthocytes, and schistocytes. Bite cells are associated with oxidant stress to the red blood cell. They can be found in normal individuals receiving large quantities of aromatic drugs (or their metabolites) containing amino, nitro, or hydroxy groups, or in patients with red-cell enzymopathies involving the pentose phosphate shunt (most notably G-6-PD deficiency, pyruvate kinase deficiency) during acute hemolytic episodes following exposure to oxidant stress. If indicated, a Heinz body test, G-6-PD level, and other studies of red blood cell metabolism may be indicated.
Blister cells are red blood cells with vacuoles or markedly thin areas at periphery of membrane. These cells are characteristic of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and other conditions imposing oxidant stress on the erythrocyte.
Codocytes ("target cells") are thin, hypochromatic cells with a round area of central pigmentation. Codocytes are characteristically seen after splenectomy, and in patients with thalassemia, and certain hemoglobinopathies (hemoglobin SS, SC, CC, EE, AE, sickle cell-thalassemia). They are also found in association with iron deficiency anemia, liver disease, and familial lecithin-cholesterol acyltransferase (LCAT) deficiency. If indicated, hemoglobin electrophoresis, liver function evaluation, serum iron studies, serum lipid profile and/or other studies may be indicated.
Dacrocytes ("tear drop cells") are red blood cells in the shape of a teardrop. Microcytosis and hypochromia usually accompany them. Dacrocytes are characteristically seen in relatively large numbers in patients with myelophthisic anemia (particularly myelofibrosis with myeloid metaplasia), but can be found in moderate numbers in megaloblastic anemia, beta-thalassemia, renal failure, tuberculosis, Heinz body disease, acquired hemolytic anemia, hypersplenism, and other hematologic diseases. Teardrop cells are pathologic and usually indicate significant bone marrow dysfunction. Clinical correlation and patient follow up is essential.
Drepanocytes ("sickle cells") are curved, irregular red blood cells with pointed ends, which are characteristic of the "sickle" hemoglobinopathies. Diseases with Hb S (sickle cell anemia, hemoglobin SC disease, hemoglobin S-beta-thalassemia, hemoglobin SD disease, hemoglobin Memphis/S disease) are the usual cause, but drepanocytes can also be seen in other hemoglobinopathies (especially Hb I, Hb C-Harlem, Hb C Capetown). A sickle cell screen and/or hemoglobin electrophoresis may be indicated.
Echinocytes ("sea urchin cells") are red blood cells with multiple tiny spicules (10-30) evenly distributed over the cell surface. These cells result from exposure of the red cell to fatty acids, lysolecithin, amniotic compounds, elevated pH, and other substances. They occur post-splenectomy, after the administration of heparin, in the hemolytic-uremic syndrome, and in hepatitis of the newborn, pyruvate kinase deficiency, phosphoglycerate kinase deficiency, uremia, and malabsorption states.
Burr cells ("crenated cells") are similar in appearance, but show an uneven distribution of spicules. Burr cells are characteristically seen in uremia, where they represent damaged or fragmented red blood cells.
Fig. 7. Representative examples of red blood cells with abnormal morphology.
Elliptocytes are cells with an elliptical shape, while ovalocytes have an oval shape. Severe elliptocytosis (> 10% elliptocytes) is characteristic of hereditary elliptocytosis, but can be prominent in thalassemia, sickle cell trait, and Hb C trait. Elliptocytic hemolytic anemia (< 10% has been reported in association with cirrhosis, decreased erythrocyte glutathione, and with glucose-6-phosphate deficiency. Other diseases where elliptocytosis occurs include iron deficiency anemia, megaloblastic anemia, myelophthisic anemia, and mechanical trauma. Rare elliptocytes (< 1%) occur in normal peripheral blood smears. If clinically indicated, osmotic fragility evaluation, hemoglobin electrophoresis, and studies of red blood cell metabolic activity may be indicated for further evaluation of patients with elliptocytosis.
Howell-Jolly bodies are small (1 mm) dense, perfectly round basophilic red cell inclusions which represent nuclear material derived from nuclear fragmentation ("karyorrhexis) or incomplete nuclear expulsion during normoblastic maturation. Howell-Jolly bodies produced in non-diseased individuals are effectively removed by the spleen and are not visible in the circulation. However, Howell-Jolly bodies are readily identified in splenectomized patients and may also be seen in smaller numbers in patients with megaloblastic anemia, severe hemolytic processes, hyposplenism, and myelophthisitic anemia.
Hypochromia is a decreased amount (MCH) and concentration (MCHC) of hemoglobin in red blood cells. In the peripheral blood smear, hypochromic cells have an expanded central zone of pallor. Small hypochromic red blood cells (microcytes) are usually present, and the mean corpuscular volume (MCV) is decreased. Microcytosis and hypochromia are characteristic of iron deficiency anemia and other microcytic, hypochromic anemias [anemia of chronic disease, hereditary hemoglobinopathies with diminished globin synthesis (thalassemias, hemoglobin E, hemoglobin H), red blood cell enzyme deficiencies (sideroblastic anemias, lead poisoning, pyridoxine deficiency)]. Serum iron studies, erythrocyte sedimentation rate (ESR), hemoglobin electrophoresis, bone marrow examination, and serum and urine lead quantitation are other laboratory studies may be indicated.
Fig. 8. Comparison of normal peripheral blood smear and smear from a patient with severe microcytic, hypochromic anemia.
Hyperchromia is an increase in the red blood cell hemoglobin concentration (MCHC > 36 g/dL). Since it is usually associated with spherocytosis, peripheral smear examination reveals many spherocytes and microspherocytes. Consideration of hereditary spherocytosis is recommended, but spherocytes are also seen in patients with isoimmune and autoimmune hemolytic anemias, Heinz body hemolytic anemia, hereditary pyropoikilocytosis, and severe burns. If indicated, an osmotic fragility assay, Coombs’ test, serum bilirubin, LDH, and haptoglobin, and other laboratory assays may be indicated.
Keratocytes ("horn cells, helmet cells") and schistocytes ("fragmented cells") are damaged red blood cells. Such damage characteristic occurs from fibrin deposits (DIC, microangiopathic hemolytic anemia, thrombotic thrombocytopenic purpura (TTP), prosthetic heart valves, severe valvular stenosis, malignant hypertension, or march hemoglobinuria. However, keratocytes and schistocytes also occur in normal newborns and in patients with bleeding peptic ulcer, aplastic anemia, pyruvate kinase deficiency, vasculitis, glomerulonephritis, renal graft rejection, severe burns, iron deficiency, thalassemia, myelofibrosis with myeloid metaplasia, hypersplenism and post-splenectomy, and other diseases. Clinical correlation is recommended, with the appropriate diagnostic studies. These cells are pathologic and should never be ignored.
Knizocytes ("pinch bottle cells") are characteristically seen in patients with hemolytic anemia, including hereditary spherocytosis. An osmotic fragility assay, Coombs’ test, serum bilirubin, LDH, and haptoglobin, and other laboratory assays may be indicated.
Oval macrocytes ("macroovalocytes, megalocytes") are large oval red blood cells (> 8.5 mm) with an elevated MCV (> 100 fL, frequently > 120 fL) and normal MCH. The presence of these cells suggests impaired bone marrow DNA synthesis, and may indicate a vitamin B12 or folate deficiency. Serum vitamin B12 or folate levels are usually indicated and a bone marrow examination may be needed.
Round macrocytes are slightly to moderately larger than normal (macrocytosis, MCV >95 fL but usually < 120 fL) and are round in shape. This finding suggests impaired bone marrow impaired DNA synthesis, stress erythropoiesis, or excessive surface membrane. Possible clinical causes include liver disease (obstructive jaundice, alcoholism), impaired DNA synthesis from chemotherapy or inherited diseases, myeloproliferative disorders, myelodysplastic syndromes, or splenectomy. Bone marrow examination, liver function studies, and other laboratory assays if clinically indicated.
Fig. 9. Comparison of normal peripheral blood smear and smear from a patient with severe microcytic, hypochromic anemia.
Microcytes are small red blood cells (MCV < 80 fL) with decreased amounts of hemoglobin formed as a result of iron deficiency and defective hemoglobin synthesis, imbalance of globin chains, or defective porphyrin synthesis. Possible clinical causes of microcytosis include iron deficiency anemia, thalassemia, the anemia of chronic disease, lead poisoning, and sideroblastic anemias.
Nucleated red blood cells
Nucleated red blood cells (NRBCs, normoblasts) are immature red blood cells. In an adult, the presence of NRBCs indicates markedly accelerated erythropoiesis and/or severe bone marrow stress. Clinical conditions associated with peripheral normoblastosis include acute bleeding, severe hemolysis, myelofibrosis, leukemia, myelophthisis, and asplenia. The presence of NRBCs in the peripheral blood of an adult always indicates a significant disease process, the etiology of which must be delineated. NRBCs in the peripheral blood of an infant indicates significant stress but does not have the ominous significance of features of those in an adult.
Poikilocytosis is variation in red blood cell shape, seen in many disorders.
Polychromasia ("polychromatophilia") is the occurrence of slightly immature red blood cells, which are larger than normal (increased MCV) and have a blue-gray coloration. Polychromasia is due to the presence of ribosomal protein in immature red blood cells, which pick up the basophilic component of the Wright-Giemsa stain. Small numbers of these cells (0.5 - 2%) are normally present in the peripheral blood and signify the presence of erythropoietic activity in the bone marrow. They are increased in states of increased erythropoietic activity in response to anemia or the iatrogenic administration of erythropoietin or another marrow stimulatory agent. The MCV may increase slightly in response to significant polychromasia. Decreased polychromasia is seen with hypoproliferative marrow states.
Rouleaux formation ("pseudoagglutination") is a linear arrangement of RBCs ("coinstack") caused by an increased blood concentration of fibrinogen, globulin, or paraproteins. Associated clinical disorders include acute and chronic inflammatory disorders, Waldenstrom’s macroglobulinemia, and multiple myeloma. Serum and urine protein analysis should be performed in the absence of an acute or chronic inflammatory disease to determine if a paraprotein is present.
Spherocytes are small (< 6.5 mm), dense spheroidal RBCs with normal or decreased MCV and absent central pallor. Hereditary spherocytosis is likely if large numbers of spherocytes are present and other forms of abnormal RBCs are absent. Small numbers of spherocytes, in combination with other abnormal RBCs, are seen in patients with isoimmune and autoimmune hemolytic anemias, Heinz body hemolytic anemia, hereditary pyropoikilocytosis, microangiopathic hemolytic anemia, hypersplenism and post-splenectomy, myelofibrosis with myeloid metaplasia, hemoglobinopathies, malaria, liver disease, recent transfusions, and severe burns. An osmotic fragility assay, Coombs’ test, serum bilirubin, LDH, and haptoglobin, and other laboratory assays may be indicated.
Stomatocytes are uniconcave red blood cells with a slit-like area of central pallor. A predominance of stomatocytes is characteristic of hereditary stomatocytosis (a type of hemolytic anemia). Small numbers of stomatocytes (usually in association with other abnormal RBCs) occur in patients with acute alcoholism, cirrhosis, obstructive liver disease, advanced malignancy, severe infections, Rhnull disease, treated acute leukemia, and other diseases.
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