Red Blood Cell Abnormalities in Morphology:
Poikilocytosis-Variation in RBC shape:
Anisocytosis: Variation in RBC shape may include larger, smaller, teardrop-shape, acanthocytes (look like spurs), echinocytes (look like burrs), oval-shape, etc... as seen in the slide above. Dimorphic RBC populations include 2 variations of shape. Seen above:
- Macrocytes (larger)
- Polychromasia (blue-purple)
- Acanthocytes (spurs)
- Echinocytes (burrs)
- Spherocytes
- Microcytes (smaller)
- Schistocytes (fragments)
- Keratocytes (helmet cells)
- Dacrocytes (teardrop)
- Non-distinctive
- Acanthocytes (Spike/Spur Cells): resemble the spurs on cowboy boots
- Codocytes (Target Cells): resemble targets or "bull's eyes"
- Dacrocytes (Teardrop Cells): resemble teardrops or raindrops
- Degmacytes (Bite Cells): resemble cells that look as if they have a bite taken out of them
- Drepanocytes (Sickle Cells): resemble sickles
- Echinocytes (Burr Cells): resemble burrs
- Elliptocytes/Ovalocytes: elliptical or oval-shaped cells
- Keratocytes (Horn Cells): resemble horns
- Microspherocytes: smaller
- Macrocytes: larger
- Pyropoikilocytes
- Schistocytes (Helmet Cells): resemble Army helmets
- Spherocytes (Microcytes): smaller
- Stomatocytes (Mouth Cells): cells are swollen, so they look as if they are mouths
Anisocytosis: Variation in RBC size/diameter
Anisocytosis means that a patient's erythrocytes are not of equal size. Red Cell Distribution Width (RDW) is a measurement of anisocytosis. If the RDW is >14.5%, this indicates a heterogenous population of RBC's, which means you will likely see a variety of sizes of RBC's on the slide. This is associated with iron deficiency, megaloblastic or hemolytic anemia.
- Microcytes (iron-deficiency anemia, sickle cell anemia): cells are smaller than usual
- Macrocytes (Folate deficiency, Vitamin B12 deficiency, Autoimmune hemolytic anemia, Cytotoxic chemotherapy, Chronic liver disease, Myelodysplastic syndrome): cells are larger than normal (oval or round)
- Normocytes (Early onset iron-deficiency anemia, Early onset folate or vitamin B12 deficiency, dimorphic anemia, sickle cell disease, chronic liver disease, myelodysplastic syndrome): cells are adequate in size
Dimorphic Population of RBC's:
A dimorphic population of RBC's means that 2 populations of RBC's are seen, and the RDW will be >14%. These are associated with:
- transfusion
- myelodysplastic syndrome
- vitamin B12, folate or iron deficiency
Hypochromia:
Hypochromia means that the central pallor zone of the red blood cell is pale. This central area must be > than 1/3rd of the diameter of the cell before it is termed hypochromic. The MCHC is a gage of hypochromia unless only a few hypochromic cells are seen in the slide. It is associated with:
- iron-deficiency anemia
- thalassemias
- sideroblastic anemia
- lead poisoning
- chronic inflammation
Polychromasia:
Polychromasia is a lavender-bluish color to RBC's due to RNA retained in larger, immature cells (macrocytes). They are associated with:
- acute and chronic hemorrhage
- hemolysis
- neonates
- treatment for anemia
Poikilocytes:
Acanthocytes (Spur Cells/Spike Cells)-Resemble spurs on cowboy boots):
Acanthocytes are red blood cells with irregular projections varying in width, length and number. They are also called "spur cells" or "spike cells", because they resemble spurs on cowboy boots. They are characterized by the following:
They are associated with:
- 3-20 spicules with narrow bases that are distributed unevenly
- spicules are sharp or knobby
- microcytes
- lack central pallor, which differentiates them from echinocytes
- seen in older blood cells or older samples
- found in post-splenectomy states very commonly
- always associated with pathological conditions
- large numbers seen in abetalipoproteinemia or advanced liver disease
- cell membrane damaged due to a decrease in membrane cholesterol
They are associated with:
- severe liver disease (hepatitis, ascites, cirrhosis, cancer, gallstones, toxicity, etc...)
- splenectomy (removal of spleen)
- malabsorption
- hypothyroidism
- vitamin E deficiency
- abetalipoproteinemia
- burns
- microangiopathic hemolytic anemia
- hemolytic uremic syndrome
- thrombotic thrombocytopenic purpura
- disseminated intravascular coagulation
- renal graft rejection
- COPD
Conditions these are seen in:
- Abetalipoproteinemia
- Liver disease
- Burns
- Chorea acanthocytosis
- McLeod Syndrome
- Neuroacanthocytosis
- Anorexia nervosa
- Infantile pyknocytosis
- Hypothyroidism
- Idiopathic neonatal hepatitis
- Alcoholism
- Congestive splenomegaly (enlarged spleen)
- Chronic granulomatous disease
- Uremia
Elliptocytes/Ovalocytes:
These cigar-shaped erythrocytes are seen in the following conditions:
- Hereditary elliptocytosis
- Spherocytic elliptocytosis
- Southeast Asian ovalocytosis
- Thalassemia major
- Iron deficiency anemia
- Myelophthisic anemias
- Megaloblastic anemias
Codocytes/Target Cells:
Codocytes are called "target cells" because they look like "bull's eyes" with a central concentration of hemoglobin surrounded by a colorless zone with a peripheral ring of hemoglobin. Conditions Codocytes are seen in:
- Iron-deficiency anemia
- Liver disease
- Thalassemia
- Hemoglobin C Disease
- Sickle Cell Anemia, if spleen removed due to
- Post-splenectomy
- Hemoglobinopathies
Stomatocytes/Mouth Cells/Slit Cells:
Conditions these are seen in:
- Hereditary stomatocytosis
- Hemolytic anemia
- Overhydration (too much water, edema, too much IV fluid)
- Also referred to as "volume overload"
- Alcoholism
- Liver disease
- Rh-null phenotype
- Artifact
Dacrocytes/Teardrop Cells:
Conditions these are seen in:
- Myelophthisic anemia-a severe anemia that is seen with some diseases affecting the bone marrow, such as granulomas, tumors
- Myelofibrosis-seen with myeloproliferative disorders, such as leukemia, lymphoma, myeloma, metastatic carcinoma
- Thalassemias
- Myelophthisic anemias
- I see these a lot in organ failure, hypoxemia, respiratory distress, liver failure
Degmacytes/Bite Cells:
Bite cells are caused by the removal of hemoglobin by the spleen. Glucose-6-phosphate dehydrogenase deficiency also causes the formation of bite cells as hemoglobin breaks down and Heinz bodies form. Bite cells may contain one or more "bites".
Echinocytes/Burr Cells:
Echinocytes are red blood cells with abnormal cell membranes that cause them to appear "spiked" or like a sea urchin. For this reason, they are also called Burr cells. They have short, evenly spaced projections. This condition is reversible, and more often than not, it is a side effect of the EDTA anticoagulant coating in the vacutainer used to collect to blood to prevent it from clotting. These cells are crenated (shrunken). Sometimes, they are associated with disorders such as:
- uremia (kidney problems) and renal failure
- hypokalemia
- bleeding peptic ulcers
- liver disease
- deficiency of vitamin E
- hyperlipidemia
- hemolytic anemia,
- pyruvate kinase deficiency,
- low levels of magnesium and/or low levels of phosphate (decreased Mg/Phos on Chemistry tests)
- microangiopathic hemolytic anemia
- myeloproliferative disorders
- heparin therapy
- post-transfusion
- artifacts
Drepanocytes/Sickle Cells:
Conditions these are seen in:
Hemoglobin CC Crystals are found in homozygous hemoglobin C disease.
- Sickle Cell Disease
- Homozygous hemoglobin S disease
- Hemoglobin SC (RBCs may look like they have 1-2 "finger-like" projections
- Homozygous hemoglobin S disease
- Sickle Cell Anemia
- Sickle Cell Crisis
- Vaso-occlusive Crisis
- Splenic Sequestration
- Aplastic Crisis
- Hemolytic Crisis
Hemoglobin CC Crystals are found in homozygous hemoglobin C disease.
Sickle Cell Disease:
Sickle cell disease is actually a group of genetic blood disorders. Sickle cell anemia is the most common type of sickle cell disease. Oxygen-carrying hemoglobin found in red blood cells is abnormal and misshapen, resulting in the rigid sickled red blood cells.
The genetics behind sickle cell disease results when an individual inherits two abnormal copies of the hemoglobin gene on chromosome 11, one from each parent. It is an autosomal recessive disease. Sickle cell trait is simply when an individual inherits just one copy of the abnormal hemoglobin gene from one parent. Such an individual is referred to as a carrier, even if asymptomatic, and may pass the abnormal gene on to their own offspring.
The genetics behind sickle cell disease results when an individual inherits two abnormal copies of the hemoglobin gene on chromosome 11, one from each parent. It is an autosomal recessive disease. Sickle cell trait is simply when an individual inherits just one copy of the abnormal hemoglobin gene from one parent. Such an individual is referred to as a carrier, even if asymptomatic, and may pass the abnormal gene on to their own offspring.
Sickle Cell Crisis:
Sickle cell crisis results in pain, anemia, edema, organ problems or failure, infections, and can also lead to stroke due to clogging up of the blood vessels with the sickled cells. A shortened life span may occur in individuals with sickle cell disease. A few examples of things that can trigger an attack include changes in temperature, altitude changes (travelling to high altitude), dehydration, and even stress.
Keratocyte/Horn Cell:
Keratinocytes are formed when the nucleus is removed by the spleen.
Spherocytes/Microcytes:
Spherocytes are seen in the following conditions:
- Auto-hemolytic anemia
- Warm hemolytic anemia
- Microangiopathic hemolytic anemia
- Hereditary spherocytosis
- Autoimmune hemolytic anemia
- Severe burns
- Transfused RBC's
Slide Image of Hereditary Spherocytosis:
Schistocytes/Helmet Cells: Fragmented RBCs
These are seen in the following conditions:
- Microangiopathic Diseases
- Disseminated Intravascular Coagulation (DIC)
- Thrombosis
- Trauma
- Severe burns
- Hemolytic Anemia
- Consequence of an artificial mechanical heart valve
- Hemolytic Uremic Syndrome (HUS), a complication of stool pathogen E.coli 0157:H7 (Enterohemorrhagic E. coli), which damages the kidneys
- TTP
- Aortic stenosis
- Atherosclerosis
Rouleaux (Stacked Coin):
Rouleaux is when RBC's are arranged in rows like "stacked coins" due to an increase in proteins. is seen in the following conditions:
- Multiple Myeloma (MM, a type of blood cancer)
- Plasma cell myeloma
- Lymphoplasmacytic lymphoma
- Infections
- Inflammatory and Connective Tissue Disorders
- Cancers
- Diabetes Mellitus
- Occlusion in Diabetic retinopathy
- Increased concentrations of globulins or paraproteins
- Clumping may be seen in antigen-antibody reactions (such as a transfusion reaction)
Red Blood Cell Agglutination:
Red blood cells stick together in clumps due to proteins called agglutinins.
RED BLOOD CELL INCLUSIONS:
Normal red blood cell cytoplasm typically does not contain any debris, granules, or structures. Red blood cell inclusions result from specific circumstances or conditions discussed below. The four most common RBC inclusions are Howell-Jolly bodies, Pappenheimer bodies, Heinz bodies and basophilic stippling.
Howell-Jolly Bodies:
Howell-Jolly Bodies are remnants of nuclear DNA in red blood cells. During the maturation process, erythrocytes exude their nucleus in the bone marrow just before becoming reticulocytes. The portion which remains in some cases is referred to as a Howell-Jolly Body. This is a reflection of abnormal mitosis. During the journey through the spleen, the spleen typically removes the Howell-Jolly Body, therefore, its presence in a peripheral blood smear usually represents the absence of the spleen or a damaged spleen. You will only see 1-2 of the round, dark, deep purple structures per cell. They are only about 1-2 micrometers in size. You will only see them when erythropoiesis is rushed. The Howell-Jolly Body could be a remnant of the nucleus of the orthochromic normoblast as it is extruded from the cytoplasm. In certain anemias, however, the spleen cannot keep up the pace since the bone marrow is responding too quickly to replace lost red blood cells.
- Seen postsplenectomy
- Hyposplenism
- Megaloblastic anemias
- Hemolytic anemias
Basophilic Stippling:
Basophilic stippling coarse, dust-like dots represent ribosomes and polyribosomes (RNA in precipitated aggregates). Cells containing these granules are often polychromatophilic, so they may be difficult to distinguish. It is seen whenever erythropoiesis is rushed, or in lead poisoning. They may be normal, or they may be a result of the following conditions:
- Sideroblastic anemia
- Myelodysplastic syndrome
- Lead poisoning
- Arsenic poisoning
- Beta thalassemia
- Alpha thalassemia
- Hereditary Pyrimidine 5'-Nucleotidase Deficiency
- Thrombotic Thrombocytic Purpura (TTP)
Ringed Sideroblasts:
Ringed sideroblasts are seen in abnormal deposition of iron in erythrocytes within the mitochondria (ATP energy-producers of the cell). The result is a ring around the nucleus. Conditions these are seen in include:
- Iron-overloading disorders (Hereditary hemochromatosis)
- Sideroblastic anemia (Congenital or Acquired)
- Refractory Anemia with Ringed Sideroblasts (RARS)
- In this type, 15% or more of RBC precursors are ringed sideroblasts
- Bone marrow: erythroid hyperplasia, <5% myeloblasts, iron overload, and hepatosplenomegaly
- In this type, 15% or more of RBC precursors are ringed sideroblasts
- Myelodysplastic disorder
- Acute myelogenous leukemia (AML)
- Megaloblastic anemia
Hemoglobin C Crystals:
These dark red, hexagonal crystals are shaped like bacilli rods and stain pink-red, are thick, and sometimes can be confusing to new techs who may mistake them for bacteria. They are composed of hemoglobin C and are associated with homozygous hemoglobin C disease. They may have a Washington Monument appearance. This abnormal hemoglobin is a glutamic acid substitution for lysine at the 6th position on the Beta-chain. Many people do not experience any signs or symptoms related to this abnormality, however, if they do, signs and symptoms may include the following:
The hemoglobin C crystals are commonly found along with target cells and microspherocytes on the hematology slide.
- Enlarged spleen
- Hemolytic anemia
- Mild anemia
- Jaundice
- Gallstones
- Sporadic joint pain
The hemoglobin C crystals are commonly found along with target cells and microspherocytes on the hematology slide.
Hemoglobin H Crystals:
Hemoglobin H crystals are associated with Hemoglobin H disease. These cells are stained with Brilliant Cresyl Blue stain which stain Hemoglobin H bodies composed of beta globin chains in tetrads. This is indicative of alpha-Thalassemia. An impaired formation of alpha-chains leads to an overage of beta-chains. This results in a moderately severe anemia. Symptoms may include jaundice, fatigue, gallstones, high blood pressure, and/or a pronounced forehead. This is an autosomal recessive genetic disorder. Serum iron and serum ferritin are other chemistry tests used to rule out iron-deficiency anemia since symptoms are similar.
Hemoglobin SC Crystals:
Hemoglobin SC crystals are composed of hemoglobin S and hemoglobin C, and they resembled a gloved hand. They are referred to as glove cells. Hemoglobin SC is a type of sickle cell disease. It affects the shape of the red blood cells. Anemia, fatigue, and severe pain are symptoms of this disease.
Macrocytes and Macrocytosis:
Macrocytes are larger than normal erythrocytes prematurely released from the bone marrow and are seen in the following conditions:
- Liver disease
- Alcoholism
- Megaloblastic Anemia
- Vitamin B12 deficiency
- Folate deficiency
- Pregnancy
- Newborns
- Aplastic anemia
- Hypothyroidism
Microcytes and Microcytosis:
Microcytes are erythrocytes that are smaller than normal, and are seen in the following conditions:
- Hypochromia in iron-deficiency anemia
- Thalassemia trait or thalassemia minor
- Congenital sideroblastic anemia
- Anemia of chronic disease
- Lead poisoning
- Some hemoglobinopathies
Hypochromic Cells:
Associated with:
The central pallor zone of the erythrocyte is greater than 1/3rd of the diameter of the erythrocyte. This is referred to as hypochromia.
- Iron deficiency anemia
- Thalassemia
- Sideroblastic anemia
- Lead poisoning
- Some cases of chronic disease
The central pallor zone of the erythrocyte is greater than 1/3rd of the diameter of the erythrocyte. This is referred to as hypochromia.
Heinz Body:
Heinz Bodies are precipitated, denatured hemoglobin in erythrocytes and are associated with hemolytic anemia. They are large inclusions ranging from 1-3 micrometers in size. They are round towards the periphery of the red blood cell. Bite cells are evidence that a Heinz Body had been formed then removed by the spleen. Other conditions that Heinz Bodies may be seen in include the following:
- NADPH deficiency
- G6PD deficiency
- Hemoglobin Zurich
- Any other unstable hemoglobin diseases
- Chronic liver disease
- Alpha-thalassemia
- Asplenia or damaged spleen
Pappenheimer Bodies:
Pappenheimer bodies are light blue-to-purple fine, irregular granules in clusters found in RBCs. They are composed of iron. They are also referred to as siderotic granules. They are seen in the iron loading processes and iron-overloading, such as hereditary hemochromatosis and iron-loading anemias. They are tiny, light purple, beaded inclusions found along the periphery of the red blood cells. Prussian Blue staining is often used to confirm this. Be careful not to mix these up with Gram-positive cocci bacteria, which look similar. They are associated with the following conditions:
- Splenectomy
- Hemolytic anemia
- Sideroblastic anemia
- Megaloblastic anemia
- Hemoglobinopathies
Cabot Rings:
Cabot rings are dark blue to purple loops, rings or figure-eights found in RBCs, and are associated with remnants of the mitotic spindle. They are associated with:
- myelodysplastic syndrome
- megaloblastic/pernicious anemia
- postsplenectomy
Dyserythropoiesis:
- Acquired iron deficiency
- Defective RBC production
- Medications can cause it
- Thalassemia
- Nutritional deficiency
- PKD
- Hereditary pyropoikilocytosis
- Abetalipoproteinemia
- HIV
- Myelodysplasia
Bite Cells:
- Seen in some hemolytic anemias
- Precipitated hemoglobin or denatured hemoglobin occurs
- Usually a defect of an RBC enzyme in which a Heinz Body is removed by the spleen, so the cell looks like it's had a "bite" taken out of it
- Caused by some types of drugs
- Caused by cirrhosis of the liver
Blister Cells:
- A pseudo-vacuole in the RBC membrane is formed by the disruption of fibrin
Pancytopenia:
All cell lines are affected: Red blood cells, White blood cells, Platelets
This abnormal slide shows the following:
This abnormal slide shows the following:
- Thrombocytopenia
- Large platelet
- Giant platelet
- Pelger-Huet cell with agranulation and vacuoles
- Anisocytosis with schistocytes, bite cells, macrocytes, microcytes, rbc aggregation, hypochromia, ovalocytes, one cell with Pappenheimer bodies
Babesia:
Malaria: Plasmodium species
Plasmodium falciparum
Plasmodium malariae
Plasmodium vivax
Plasmodium ovale
Plasmodium knowlesi