Version 1
October, 1999

Classification of RBC Morphologic Abnormalities

Roger S. Riley, M.D., Ph.D.
Department of Pathology
Medical College of Virginia

RBC Abnormality
Description of Cells
Associated Conditions
Normal erythrocytes
("Discocytes," "normocytes")
Round to slightly ovoid biconcave disks, approximately 7 m in diameter. Less hemoglobin in center of cell (zone of pallor). Regular in size and shape. Normal individuals.
Acanthocyte
("Spur cells")
Spheroid RBCs with few large spiny projections. 5-10 spicules, irregular spacing and thickness (must be differentiated from echinocytes). Abetalipoproteinemia, postsplenectomy, alcoholic cirrhosis and hemolytic anemia, microangiopathic hemolytic anemia, autoimmune hemolytic anemia, sideroblastic anemia, thalassemia, severe burns, renal disease, pyruvate kinase deficiency, McLeod phenotype, infantile pyknocytosis, post-splenectomy.
Autoagglutination Irregular RBC agglutination/clumping resembling Chinese letters. Anti-RBC antibody, paraprotein. Cold agglutinin disease, autoimmune hemolytic anemia, macroglobulinemia, hypergammaglobinemia
Basophilic stippling Fine, medium, or coarse blue granules uniformly distributed throughout RBC. Fine stippling - polychromatophilia. Coarse stippling - Impaired erythropoiesis. Heavy metal poisoning (e.g. lead and arsenic), hemoglobinopathies, thalassemias, sideroblastic anemias, pyrimidine-5’-nucleotidase deficiency
Bite cells ("Degmacytes") RBCs with peripheral single or multiple arcuate defects. Usually associated with spherocytes and blister cells. Oxidant stress. Normal individuals receiving large quantities of aromatic drugs (or their metabolites) containing amino, nitro, or hydroxy groups. Individuals with red-cell enzymopathies involving the pentose phosphate shunt (most notably G6PD deficiency.
Blister cells RBCs with vacuoles or markedly thin areas at periphery of membrane. Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. Other oxidant stress.
Codocytes
("Target cells")
Thin, hyopochromatic cell. Round area of central pigmentation. Splenectomy, thalassemia, hemoglobinopathies (hemoglobin SS, SC, CC, EE, AE, sickle cell-thalassemia), iron deficiency anemia, liver disease, postsplectomy, familial lecithin-cholesterol acyltransferase (LCAT) deficiency.
Dacrocytes
("Tear drops")
Cell in shape of tear drop. Usually accompanied by microcytosis and hypochromia Myelophthisic anemia (particularly myelofibrosis with myeloid metaplasia), magaloblastic anemia, b-thalassemia, anemia of renal failure, tuberculosis, Heinz body disease, hemolytic anemias, hypersplenism.
Drepanocytes
("Sickle cells")
Irregular, curved cells with pointed ends Hb S hemoglobinopathies (sickle cell anemia, hemoglobin SC disease, hemoglobin S-beta-thalassemia, hemoglobin SD disease, hemoglobin Memphis/S disease), other hemoglobinopathies (especially Hb I, Hb CHarlem, HbCCapetown).
Echinocytes
("Sea urchin cells,
crenated cells, burr
cells")
RBC with many tiny spicules (10-30) evenly distributed over cell Post-splenectomy, uremia, hepatitis of the newborn, malabsorption states, after administration of heparin, pyruvate kinase deficiency, phosphoglycerare kinase deficiency, uremia, HUS.
Elliptocytes RBCs with elliptical or oval shape Hereditary elliptocytosis, thalassemia, sickle cell trait, Hb C trait, cirrhosis, decreased erythrocyte glutathione, glucose-6-phosphate deficiency, iron deficiency anemia, megaloblastic anemia, myelophthisic anemia, hereditary hemorrhagic telangiectasia, mechanical trauma.

Howell-Jolly bodies Small (1 mm), round, dense, basophilic bodies in RBCs. Splenectomized patients, megaloblastic anema, severe hemolytic processes, hyposplenism, myelophthistic anemia.
Hyperchromia Increased RBC hemoglobin concentration (MCHC > 36 g/dL). Usually associated with spherocytosis Hereditary spherocytosis, immune hemolytic anemias.
Hypochromia Decreased RBC amount (MCH) and concentration (MCHC). Expanded central zone of pallor Iron deficiency, other hypochromic anemias.
Keratocytes
("Horn cells")
Helmet forms Mechanical damage to red blood cells from fibrin deposits (DIC, microangiopathic hemolytic anemia, thrombotic thrombocytopenic purpura), prosthetic heart valves, severe valvular stenosis, malignant hypertension, or march hemoglobinuria, normal newborns, bleeding peptic ulcer, aplastic anemia, pyruvate kinase deficiency, vasculitis, glomerulonephritis, renal graft rejection, severe burns, iron deficiency, thalassemias, myelofibrosis with myeloid metaplasia, hypersplenism
Macrocyte


"Thin" macrocyte
Large RBCs (> 8.5 mm, MCV > 95 fL). Normal MCH

Increased diameter, normal MCV. Usually hypochromic
Accelerated erythrocytosis. Macrocytic anemia (B12 or folate deficiency)(oval macrocytes)

Liver disease, postsplenectomy
Microcyte Small RBCs (< 7.0 mm, < 80 fL). Normal or decreased Hb Iron deficiency, thalassemias, anemia of chronic disease, lead poisoning, sideroblastic anemia
Nucleated red blood
cells ("NRBCs")
Immature RBCs, basophilic nucleus. Acute bleeding, severe hemolysis, myelofibrosis, leukemia, myelophthisis, asplenia.
Poikilocytosis Variation in RBC shape. Many disorders.
Polychromasia ("Polychromatophilia") Blue-gray coloration of RBCS. Due to mixture of RNA and hemoglobin. Increased - Increased erythropoietic activity. Decreased - Hypoproliferative states.
Rouleaux Linear arrangement of RBCs,"coinstack." Increased fibrinogen, globulins, or paraproteins (compare with autoagglutination, above). Acute and chronic inflammatory disorders, Waldenstroms macroglobulinemia, multiple myeloma.
Schistocytes
("Fragmented cells")
Fragmented RBCs (compare with keratocytes, above) Mechanical damage to red blood cells from fibrin deposits (DIC, microangiopathic hemolytic anemia, thrombotic thrombocytopenic purpura), prosthetic heart valves, severe valvular stenosis, malignant hypertension, or march hemoglobinuria, normal newborns, bleeding peptic ulcer, aplastic anemia, pyruvate kinase deficiency, vasculitis, glomerulonephritis, renal graft rejection, severe burns, iron deficiency, thalassemias, myelofibrosis with myeloid metaplasia, hypersplenism
Spherocytes RBCs with spheroidal shape. Usually dense, small (< 6.5 mm) RBCS with normal or decreased MCV, and absent central pallor Hereditary spherocytosis and hemolytic anemias (isoimmune or autoimmune), microangiopathic hemolytic anemia, hypersplenism and post-splenectomy, myelofibrosis with myeloid metaplasia, hemoglobinopathies, malaria, liver disease, older population of transfused cells, artifact. Microspherocytes in severe burns and hereditary pyropoikilocytosis.
Stomatocyte
(Fish mouth cell")
Uniconcave RBC, slitlike area of central pallor Hereditary or acquired hemolysis. Hereditary stomatocytosis, alcoholic cirrhosis, acute alcoholism, obstructive liver disease, malignancy, severe infection, treated acute leukemia, artifact.