Abnormal RBC types and shapes can be seen under a variety of conditions. Normal RBCs have a biconcave shape with a central pale area. Any variation in size, shape, structure, color or arrangement of RBCs represents an abnormal cell.
These abnormalities are detected by viewing the blood smear through a microscope.
Identification of the abnormal RBC type can suggest the underlying cause of the disease.
Blood consists of following major cell types
- Red Blood Cells (RBCs) or Erythrocytes
- White blood cells (WBCs) or Leucocytes
- Platelets or Thrombocytes
RBCs are the hemoglobin carrying cells that carry oxygen throughout the body.
Normal Size and Shape of RBCs
The average size of RBC is roughly equal to the size of the nucleus of a small lymphocyte with a mean diameter of about 7.5 μm.
Normal RBCs are biconcave discs. They have an area of central pallor that occupies approximately one-third of the cell’s diameter. Hence they appear lighter in the center than at the edges.
They contain no nucleus. This maximizes the amount of hemoglobin carried by these cells so as to maximize the amount of oxygen that each cell can carry.
They are very flexible. This enables the erythrocytes to squeeze into thin capillaries so that they can reach all the tissues in the body and deliver oxygen.
Abnormal RBC Types
They are found in various pathological conditions.
- Abnormal size
- Abnormal shape
- Abnormal color and pallor
- Abnormal arrangement
- Presence of inclusion bodies
Abnormal RBC Size
A normal-sized RBC is called normocyte. Variation in the size of RBCs is known as anisocytosis.
Based on the size, abnormal RBCs can be
Macrocytes
These RBCs are larger than normal. They are seen in the following conditions:
- Anemia due to Vitamin B-12 and folic acid deficiency (Megaloblastic anemia)
- Pernicious anemia
- Liver disease
- Alcoholism
Microcytes
These RBCs are smaller than normal. They are seen in
- Iron deficiency anemia
- Thalassemia
- Anemia of chronic disorders
- Sideroblastic anemia.
Abnormal RBC Shapes
Although some variation in RBC shape is normal and considered healthy, certain shapes can indicate disease.
Variation in the shape of RBC is called poikilocytosis. Abnormally or irregularly shaped RBCs are called poikilocytes.
Spherocytes
RBCs become more spherical, no central pallor is present and there is increased hemoglobin content.
They are seen in the following conditions:
- Hereditary spherocytosis
- Autoimmune hemolytic anemia
- Post transfusion reaction
- Red cell fragmentation disorders
Sickle cells (Drepanocytes)
These are sickle or crescent-shaped RBCs.
They are the characteristic feature of sickle cell anemia. They may also be seen in hemoglobin S-thalassemia.
Ovalocytes (Elliptocytes)
These are oval-shaped or cigar-shaped erythrocytes with blunt ends.
They are seen in the following conditions:
- Hereditary elliptocytosis (large number of elliptocytes are present)
- Thalassemia
- Sickle cell anemia
- Iron deficiency anemia
- Megaloblastic anemia
- Myelofibrosis
- Cirrhosis
Macro-ovalocytes
These RBCs are both enlarged in size as well as oval in shape. They are characteristically seen in megaloblastic anemia.
Target cells (Codocytes)
RBCs have a centrally located disk of hemoglobin surrounded by an area of pallor with an outer rim of hemoglobin adjacent to the cell membrane giving the cell the appearance of a target or a bull’s eye.
They are seen mainly in the following conditions:
- Iron deficiency anemia
- Thalassemia
- Post splenectomy
- Obstructive liver disease
- Hemoglobin C disorders
Teardrop cells (Dacryocytes)
Tear or pear-shaped RBCs have one rounded end and one pointed end.
They are seen mainly in the following conditions:
- Myelofibrosis
- Megaloblastic anemia
- Thalassemia
- Hemolytic anemia
- Iron deficiency anemia
Schistocytes
These are the fragmented, helmet or triangular-shaped RBCs. They are seen in the following conditions:
- Thalassemia
- Microangiopathic hemolytic anemia
- Mechanical hemolytic anemia
- Uremia
- Artificial heart valves
- Sepsis or severe infection
- Burns
Acanthocytes (Spur cells)
These are erythrocytes with irregularly spaced projections called spicules present on the cell membrane.
They are seen in the following conditions:
- Liver diseases
- Post splenectomy
- Thalassemia
- Autoimmune hemolytic anemia
- Abetalipoproteinemia
- Anorexia nervosa
- Starvation
- Alcoholism
- Vitamin C deficiency
Stomatocytes
Red cells with a central linear slit or stoma are called stomatocytes. In peripheral blood smears, they are seen as mouth shaped form.
These are seen in the following conditions
- Hereditary stomatocytosis
- Alcoholism
- Liver disease
Keratocytes
These are half-moon shaped RBCs with two or more spicules. They are seen in the following conditions
- G6PD deficiency
- Pulmonary embolism
- Disseminated intravascular coagulation
Burr cells (Echinocytes)
Similar to acanthocytes, these cells also have projections or spicules on their surface. However, these projections are evenly spaced.
They are seen in the following conditions
- Pyruvate kinase deficiency
- Kidney disease
- Megaloblastic anemia
- Liver disease
- Phosphoglycerate kinase deficiency
- Hypophosphatemia
- Hyperlipidemia
- Hemolytic anemia
- Cancer
- Myeloproliferative disorders
- Vitamin E deficiency
- Following transfusion of aged blood (burr cells may form during blood storage)
- They may also appear as an artifact of staining or drying
Leptocytes (Wafer cells)
They are thin, flat cells that have hemoglobin at the edge of the cell.
They are seen in the following conditions
- Thalassemia
- Obstructive liver disease
Abnormal RBC Color and Pallor
Normal RBCs are disc-shaped and have an area of central pallor that occupies approximately one-third of the cell’s diameter. These normal erythrocytes are known as normochromic RBCs.
Hypochromic RBCs
These cells have an area of pallor that is larger than normal.
They are seen in
- Iron deficiency anemia
- Anemia of chronic diseases
- Hemoglobinopathies
- Sideroblastic anemia
Polychromatophils
They are immature red blood cells ( reticulocytes) that contain cytoplasmic RNA fragments. They are larger than normal red cells and stain dark purple on a peripheral smear. They are distinguished from macrocytes by their distinctive color.
Under normal conditions, these immature young RBCs remain in the bone marrow for one or two days before being released into the bloodstream. However, when the bone marrow is hyperfunctioning, these cells are prematurely released into the blood. This can occur in the following conditions:
- Hemolytic anemias
- Treatment of anemia. (polychromatophils indicate that bone marrow is responding to anemia)
Abnormal RBC Arrangement or Distribution
Red cell agglutinate
RBCs are present in irregular clumps. They are seen in:
- Cold agglutination
- Warm autoimmune hemolysis
Rouleaux formation
RBCs resemble a stack of coins. It is seen in
- Multiple myeloma
- Hyperglobulinemia
- Hyperfibrinogenaemia
Presence of Inclusion Bodies
Howell-Jolly bodies
These are small round cytoplasmic red cell inclusions that have the same staining characteristics as nuclei. These are fragments of DNA. They are seen in:
- Post splenectomy
- Megaloblastic anemia
- Hemolytic anemia
Heinz bodies
These represent denatured hemoglobin (methemoglobin) within a cell. With a supravital stain like crystal violet, these appear as round blue precipitates. They are seen in:
- G6PD deficiency
- Splenectomy
Pappenheimer bodies
These represent iron deposits. They are seen as dense blue, irregular granules. They are seen in the following conditions:
- Hemolytic anemia
- Splenectomy
- Sideroblastic anemia
- Thalassemia
Basophilic stippling
These are small basophilic inclusions present in RBCs which represent precipitated RNA. They are seen in:
- Thalassemia
- Megaloblastic anemia
- Hemolytic anemia
- Liver damage
- Heavy metal poisoning
Cabbot’s ring
These are reddish, purple, thread-like rings in RBCs. They are the remnants of nuclear membrane. They are seen in megaloblastic anemia.
Signs and Symptoms
The presence of abnormal RBC types in the blood is not a disease itself but indicates the presence of an underlying disease that needs to be investigated and treated.
The signs and symptoms depend on the underlying condition.
The most common symptoms are those of anemia and include features like weakness, fatigue, poor concentration and shortness of breath. Severe anemia may have symptoms such as palpitations, angina, or heart failure.
Other symptoms may include symptoms related to liver disease, alcoholism, hemolysis, infection, etc.
On examination, the signs include pallor of skin, conjunctiva and nail beds. Specific signs may be seen such as koilonychia (in iron deficiency), jaundice (in hemolytic anemia), bone deformities (in thalassemia major) or leg ulcers (in sickle-cell disease).
Lab Investigations
- Complete blood count
- Examination of a well stained peripheral blood smear by a pathologist using a microscope
- Reticulocyte count
- ESR
- Serum iron, ferritin, transferrin, RBC folate level, serum vitamin B12
- Liver function tests
- Renal function tests
- Hemoglobin electrophoresis
- Bone marrow examination
Treatment
Treatment depends on the underlying condition and its severity. Identifying and treating the underlying cause remains the mainstay of the treatment.
If the cause is a low level of iron, vitamin B12 or folate, treatment is by taking supplements (oral or injectables) or by improving the diet.
Treating the underlying disease (like celiac disease, worm infestation, etc) that is causing the deficiency is also important.
Blood transfusions may be considered for patients having severe anemia.
Inherited forms of anemia like sickle cell anemia or thalassemia, may require regular blood transfusions or a bone marrow transplant. Liver disease may require abstinence from alcohol or a liver transplant (in case of excessive damage to the liver). Serious infections may need antibiotics while cancers are treated by chemotherapeutic drugs.
Outlook or Prognosis
Long-term outlook depends on the underlying cause.
Anemia caused due to iron deficiency or vitamin B12 or folic acid deficiency is treatable and completely curable. If not treated, it can result in serious complications especially in growing children or pregnancy
Anemia resulting from genetic disorders such as thalassemia or sickle cell anemia requires lifelong treatment. With proper treatment, many patients can lead a near-normal life.
