| Alpha Thalassemia Intermedia Alpha thalassemia intermedia (Hemoglobin H Disease) is a result from a deletion of three out of four alpha chain loci. Infants born with alpha thalassemia intermedia appear normal at birth but often develop anemia and splenomegaly by the end of their first year. Hepatomegaly is not a common finding and there may be some association with mental retardation. Due to the hemolytic nature of this anemia, there may be an increase in respiratory infections, leg ulcers and gallstones. Skeletal changes are not commonly seen in hemoglobin H disease. Every ethnic group can have occurrences of hemoglobin H disease; but it is most often seen in Southeast Asian, the Middle East and the Mediterranean islands. Development and life expectancy are usually normal, but some may require splenectomy and transfusion therapy. | View Page |
| Summary The normal RBC count (4.84 x 1012/L) in this case, together with the decreased hemoglobin (8.4 g/dL) and MCV (59 fl) is an indicator of ineffective erythropoeisis that often points to thalassemia.The RBC morphology shows slight hypochromic microcytosis with codocytes, schizocytes, and basophilic stippling. Schizocytes form by several mechanisms, one being the removal of rbc inclusions.This patient's elevated bilirubin correlates with her presentation of sclera icterus; and her splenomegaly is consistent with increased rbc destruction.The Hb electrophoresis demonstrated a normal pattern, initially, but the unstable Hemoglobin H was revealed upon repeat electrophoresis with reduced incubation time. Hemoglobin H is the result of beta globin chain tetramer formation due to the insufficient supply of alpha globin chains in alpha thalassemia intermedia.People with Hemoglogin H disease (alpha thalassemia intermedia) usually have a normal life expectancy without treatment. However, hemolysis may lead to moderate anemia that may be treated with splenectomy. | View Page |
| Pappenheimer bodies are usually seen in patients who have had: | View Page |
| More on Howell-Jolly Bodies Under normal conditions, Howell-Jolly bodies are thought to be remnants of nuclear fragments due to incomplete expulsion of the nucleus. In pathological conditions, they are aggregates of chromosomes which have separated from the mitotic spindle during abnormal mitosis. Single or multiple Howell-Jolly bodies may be found in a red cell. A single HJ body in a red cell may be seen in megaloblastic anemia, hemolytic anemia such as sickle cell anemia and after splenectomy. Megaloblastic anemia or abnormal erythropoiesis is usually present when multiple Howell-Jolly bodies are observed in a single cell. | View Page |
| In which of the following conditions would you expect to find Howell-Jolly bodies? | View Page |
| More on Pappenheimer bodies Pappenheimer bodies, while visible on a Wright's stained smear, should be Perls' Prussian blue stain, which is specific for iron. Pappenheimer bodies are seen in certain types of anemia characterized by an increase in the storage of iron, such as sideroblastic anemia and thallassemia. These inclusions are also seen in the peripheral blood following a splenectomy. In a healthy person with a normal spleen, Pappenheimer bodies are destroyed before the erythrocytes enter the peripheral circulation. | View Page |
| What are Cabot rings? Thin, red-violet-staining strands in the shape of rings, figure eights, or shapes of the letter B may on rare occasions be seen in erythrocytes. These structures are called Cabot rings. Although the origin of Cabot rings continues to be illusive, they are not nuclear fragments since they test Feulgen negative. The rings are probably microtubules remaining from a mitotic spindle. Cabot rings have been observed in a few cases of megaloblastic anemia, lead poisoning and other disorders of erythropoiesis, as well as, after a splenectomy. | View Page |
| Note the view of a peripheral blood smear in the photograph. Pictured are scattered acanthocytes, echinocytes, target cells, spherocytes, and schistocytes. The condition in which each of these atypical RBC's may be found in varying numbers in the same peripheral blood smear is: | View Page |
| Match the form of red cell inclusions in each of the frames of photographs with a corresponding clinical condition. | View Page |
| What are the erythrocyte inclusions that are indicated by the arrows on this blood smear? | View Page |
| The peripheral blood picture is consistent with each of the following conditions except: | View Page |
| The RBC inclusions shown in the photograph represent which of the following? | View Page |
| Heinz body formation Heinz bodies are 1-3 um particles of denatured hemoglobin settling eccentrically, usually close to the red cell membrane. They are found in erythrocytes in unstable hemoglobin disorders, acute drug induced hemolysis, and following splenectomy. Their formation may be exaggerated by in-vitro incubation of a fresh blood sample with phenylhydrazine. Heinz bodies, as pictured here, are identified using a supra-vital stain, such as new methylene blue or cresyl violet. Bite cells, visible with Wright-Giemsa staining, are visual reminders that the spleen is functional and has pitted the aberrant chunk of hemoglobin from the circulating erythrocyte. | View Page |
| Smear with teardrop cells As previously mentioned, tear drop cells are present in disorders with altered splenic or bone marrow structure. Disrupted splenic cords and myelofibrosis with myeloid metaplasia are examples. Tear drop cells appear in the peripheral blood as a response to red cell alterations by thalassemia when red cell inclusions are expelled by a stripping process through splenic cords. A marrow disrupted by malignant cells may also set the stage for release of teardrop cells into the peripheral blood. Importantly, teardrop cells may arise as an artifact of improper smear preparation, identified by their uniformity in pointing in the same direction. In contrast, teardrops noted in the photograph are irregularly arranged and oriented in various directions. Teardrops always have pointed ends and disappear after splenectomy. | View Page |
| Spherocytes and reticulocytes The photograph represents peripheral blood smear findings in another patient with hereditary spherocytosis. The red cells vary in size (anisocytosis)with a mixture of microcytes (red cells with central pallor) and microspherocytes (red cells with central staining). Macrocytes are conspicuous, some staining light blue. They are immature erythrocytes (reticulocytes)released from the bone marrow early. The bone marrow, geared up for rapid cell release in response to severe hemolysis, expels young red blood cells into the circulation before completing their 24 hour maturation cycle. Hemolysis, jaundice, and gall stone formation disappear following splenectomy. Gallbladder and stone removal eliminate the right upper quadrant pain. A serious consideration, especially in children with hereditary spherocytosis, is hemolytic crisis. A viral infection may allow red blood cell destruction to continue unabated. Anemia of such sudden onset and severity may become catastrophic, with death as the outcome. Splenectomy removes this possibility. | View Page |
| The photograph here is of a peripheral smear sent for hematologic review. No clinical information for the patient was sent with the slide. What is the first course of action that the reviewer should take to assist him/her in interpreting the findings on this blood smear? | View Page |
| Ways out of the dilemma What clear courses of action might the clinician take if the technologist reports out from this smear 3+ acanthocytes, 1+ target cells and occasional helmet cells? Gleaning information from the review of peripheral blood smears is important for the technologist, physician, and surely for the patient. Extreme pressures of time constraints and shifting dynamics in communication, from face-to-face encounters to dependency on technology, make innovative solutions to physician-patient information dilemmas imperative. Reporting systems often are geared more toward retrievability, suiting the needs of administrators and record keepers rather than being clearly directed toward improving patient care outcomes. A prime solution to this communication dilemma is to provide technologists with written descriptions and images of specific abnormal findings from peripheral blood smears. With a high degree of probability, these may link directly with underlying information connected to diseases. Mutually understood terms must be established to convert subjective qualitative peripheral blood smear findings into mutually understandable information. For example, regarding the smear shown, it was learned that the patient had recently undergone splenectomy. Creating an integrated communication system for information sharing (providing essential patient information by telephone follow-up or use of a system for e-mail feedback) can help ensure a favorable clinical outcome. | View Page |
| Normoblasts Many of the distorted erythrocytes displayed on the previous page are also present on this one. We see anisocytosis, poikilocytosis, fragmented forms, target cells, and a few Howell-Jolly bodies. Note also circulating nucleated red blood cells (normoblasts). The presence of these normoblasts may represent a premature release from a hyperplastic marrow or, more likely, are due to a lessening of the normal inhibition of erythroid release from the marrow as a result of splenectomy, permitting their earlier entry into the circulation. | View Page |
| Howell -Jolly bodies/ other erythrocyte environmental alterations Several erythrocyte abnormalities are present in both the upper and lower photomicrographs. Many of these atypical cells are probably present as a result of the patient's splenectomy. Considerable anisocytosis and poikilocytosis with many tear-drop cells, bite cells, fragmented forms, and a few target cells are apparent. Some of the erythrocytes in the upper frame contain Howell-Jolly bodies (DNA fragments) that may be single or multiple, especially in myeloproliferative disorders. These inclusions stain negatively for iron and are eccentrically placed in the red cell cytoplasm. . | View Page |
| Case History A 54 year-old man was brought to the clinic by his sister who was emphatic that her brother was "not taking care of himself."The patient had a previous gastrectomy and splenectomy. He also had a diagnosis of alcoholism, malnutrition, and hepatic cirrhosis. The following five pages discuss a variety of erythrocyte changes that have occurred as a result of his various conditions. | View Page |
| Pseudomacrocytes Another type of macrocyte can be seen in the center of this slide. Notice it appears larger than the lymphocyte but in contrast to megalocytes has an area of central pallor. These macrocytes are sometimes referred to as "pseudo macrocytes," since their size is the result of exaggerated flattening (leptocyte) and thus the presence of the central pallor. The MCV for this type of macrocyte is within normal range. Pseudomacrocytes can be seen in patients with cirrhosis of the liver, obstructive jaundice, post splenectomy and conditions that affect the red cell membrane. | View Page |
| More Acanthocytes Acanthocytes can also be seen in this slide. Alcoholic cirrhosis is the most common source of acanthocytes seen in blood smears in the laboratory (10-50%). Other sources are lipid disorders and a small number following splenectomy.
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| Another Target Cell Another example of a target cell (or codocyte) is seen in the center of this slide. Notice that the hemoglobin in the center of this cell is somewhat lighter in appearance than in the previous slide. A second codocyte can be seen in the upper left portion of the slide. Codocytes appear in conditions which cause the surface of the red cell to increase disproportionately to its volume. This may result from a decrease in hemoglobin, as in iron deficiency anemia, or an increase in cell membrane.
Target cells have excess membrane cholesterol and phospholipid and decreased cellular hemoglobin. Examples of other conditions in which target cells may be present include thalassemias, hgb C disease, post splenectomy and obstructive jaundice. Since their presence can be the result of an in vitro artifact, their value in clinical diagnosis is limited. | View Page |