| Anemia in alpha thalassemia In thalassemia there is often an excess production or accumulation of globin chains produced by genes that are not effected by the thalassemia deletion. In alpha thalassemia this may be seen as gamma chain tetramers (hemoglobin Bart's) in the unborn child and as beta chain tetramers (hemoglobin H) in adults. Tetramer accumulation often leads to red blood cell damage and hemolytic anemia. | View Page |
| 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 |
| Serum Bilirubin Bilirubin is formed as a result of hemoglobin degradation. Normally, senescent red blood cells are removed from circulation and the bilirubin that is formed is processed by the liver. The normal level of bilirubin in the serum of adults is 0.2-1mg/dl. Bilirubin levels increase with liver disorders and also in anemia that is a result of a hemolytic process. Patients may display jaundice when serum bilirubin levels exceed 2mg/dl.Persons with alpha thalassemia intermedia usually have an increased bilirubin level, because of ongoing hemolysis. This bilirubin is typically the unconjugated fraction of bilirubin. | View Page |
| Serum Haptoglobin Haptoglobin is the plasma protein responsible for binding free hemoglobin during episodes of hemolysis and would normally demonstrate decreased levels during a hemolytic crisis.The normal level of haptoglobin is 40-330mg/dl. Individuals who are in hemolytic crisis demonstrate greatly reduced levels to an absence of haptoglobin.In alpha thalassemia, however, haptoglobin levels remain normal or only slightly decreased, even during hemolytic events.The reason for this is that haptoglobin functions by binding the alpha chain portion of hemoglobin. With the absence of these chains in alpha thalassemia major and intermedia, haptoglobin cannot bind free hemoglobin. Therefore it is not consumed. | View Page |
| Clinical Significance No blood is found in the urine of healthy individuals although samples from menstruating females, frequently, but not always, test positive for blood. Hematuria is associated with renal or genital urinary disorders in which the bleeding is the result of irritation to the involved organs or trauma. Examples include renal calculi, pyelonephritis, glomerulonephritis, tumors, trauma or exposure to toxic chemicals or drugs and/or strenuous exercise. Hemoglobinuria may be due to the lysis of red cells within the urinary tract. If it is caused by intravascular hemolysis, the hemoglobin is then filtered through the glomeruli. In the normal individual, the hemoglobin molecule attaches to haptoglobin and in this way bypasses the kidney filtration system. When the hemoglobin/haptoglobin system is overwhelmed, as in cases of hemolytic anemia, severe burns, transfusion reaction, infection or strenuous exercise, hemoglobin passes into the urine. | View Page |
| Match the following: | View Page |
| Clinical Significance Urinary urobilinogen may be increased in the presence of a hemolytic process such as hemolytic anemia. It may also be increased with infectious hepatitis, or with cirrhosis. Comparing the urinary bilirubin result with the urobilinogen result may assist in distinguishing between red cell hemolysis, hepatic disease, and biliary obstruction. Urobilinogen is increased in hemolytic disease and urine bilirubin is negative. Urobilinogen is increased in hepatic disease, and urine bilirubin may be positive or negative. Urobilinogen is low with biliary obstruction, and urine bilirubin is positive. Reagent strips methods however, cannot distinguish normal urobilinogen from absent urobilinogen, as might be seen in complete biliary obstruction. | View Page |
| Urobilinogen is excreted in the urine in increased amounts in: (Choose ALL of the correct answers) | View Page |
| The most common cause of severe life threatening hemolytic transfusion reactions is: | View Page |
| A delayed hemolytic transfusion reaction is most likely to be the result of which of the following antibodies: | View Page |
| Which of the following types of packed RBCs could be transfused to a group O patient: | View Page |
| Fresh frozen plasma : | View Page |
| Which of the following antibodies is the most common cause of hemolytic disease of the newborn: | View Page |
| The use of the direct antiglobulin test is indicated in all the following except: | View Page |
| IgM antibodies directed against red cells generally: | View Page |
| Which of the following conditions is most frequently associated with anti-I: | View Page |
| Which of the following set of conditions would preclude hemolytic disease of the newborn as a result of ABO incompatibility: | View Page |
| To detect the presence of blocking antibodies fixed on the red cells of a newborn infant: | View Page |
| Patients with which of the following conditions would benefit most from washed red cells: | View Page |
| The most severe acute hemolytic transfusions reactions are the result of which of the following: | View Page |
| Which of the following antigen groups is closely related to the ABO system: | View Page |
| IgM antibodies produced against red blood cells generally: | View Page |
| The patient was admitted to the hospital. The sputum specimen was inoculated to sheep blood agar. Based on the colony morphology seen in the accompanying photograph, the most likely identification is: | View Page |
| Middle ear damage in cases of S. pneumoniae infections are caused primarily by: | View Page |
| The bacterial species shown growing on 5% sheep blood agar was recovered from the spun sediment of a midstream urine specimen after 24 hours incubation at 35C. Each of the following tests would be useful in supporting the presumptive identification of Enterococcus species except: | View Page |
| The spot test that is helpful in separating Enterococcus species (positive as shown in the photograph) from the viridans streptococci and S. pneumoniae (both negative) is: | View Page |
| Most strains of S. milleri (anginosus) carry the F antigen (see photograph). Rare strains that carry the group A antigen can be differentiated from S. pyogenes by which of the following laboratory tests: | View Page |
| Beta hemolytic colonies grew from the blood culture bottle after 18 hours incubation (see photograph). The following tests would be helpful in making a preliminary identification: | View Page |
| Thus, in follow-up to the previous discussion, the reaction shown in the photograph establishes the identification of a group A, beta hemolytic streptococcus. | View Page |
| Shown in the photograph is a close-in view of the colony growth after 48 hours incubation. Possible presumptive identifications suggested by the colonies observed include: | 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 |
| The condition most likely associated with the peripheral blood picture shown in the photograph is: | View Page |
| Match the form of red cell inclusions in each of the frames of photographs with a corresponding clinical condition. | View Page |
| Conditions in which erythrocytes as photographed here may be present in a peripheral blood smear include: | View Page |
| What are the erythrocyte inclusions that are indicated by the arrows on this blood smear? | View Page |
| An 8 year old girl is protected from severe hemolytic anemia by an elevated fetal hemoglobin level ( hemoglobin F). | View Page |
| The peripheral blood picture is consistent with each of the following conditions except: | View Page |
| The peripheral blood smear represented by this field was submitted for hematologic review. The RBC inclusions most likely are: | View Page |
| Schistocytes vs. bite cells Schistocyte is a general term for a fragmented red blood cell that may assume various shapes, some with horn-like projections (keratocytes), triangle-forms (triangulocytes), and helmet shapes, as illustrated in the upper photograph. Schistocytes are formed when erythrocytes are forced through a vessel blocked with interlacing fibrin strands and the red cells are sliced into fragments. True schistocytes are devoid of central pallor. These damaged cells continue to circulate while healing their torn edges. Finally, they are removed by the spleen. Bite cells (lower photograph) appear when an abnormal hemoglobin aggregate (Heinz body) is nibbled out of a red cell's cytoplasm by the spleen leaving a bitten apple appearance. Glucose 6-PD deficiency secondary to chemical poisoning or injury by oxidant drugs are settings for Heinz body formation, and the telltale bite cells remain as evidence. Hemolytic anemia associated with severe liver disease is another setting where bite cells are formed. | View Page |
| DIC: graft vs. host disease The peripheral smear illustrated in the photograph was obtained from a patient with a recent renal transplant. The patient developed a rash, accompanied by nausea and diarrhea. Graft vs. host disease was clinically suspected. The peripheral smear findings are consistent with that diagnosis. The presence of spherocytes suggests a hemolytic process which is supported by the presence of nucleated RBCs. A few scattered schistocytes and the decrease of platelets suggests DIC. The presence of target cells presents the possibility of associated liver disease. Additional tests, particularly coagulation studies, should confirm the diagnosis of microangiopathic hemolytic anemia. | View Page |
| The presence of erythrocytes with altered morphology (as photographed here) has a close association with each of the following conditions except: | View Page |
| The underlying condition where the defective erythrocytes marked by arrows are of diagnostic importance is: | View Page |
| A 5-year-old girl was brought to a physician's office because of fever and viral-type illness symptoms. Her blood pressure was elevated.Hemogram: hemoglobin 9.1g/dL (normal 12.0 - 16.0 g/dL), hematocrit 28% (normal 37 - 48%), MCV 80 fl (normal 86 - 98 fl), RDW 13.1% (normal 11 - 15%), platelets 90.1 X 109/L (normal 150 - 450 X 109/L) WBC 9.6x109/L (normal 4.3 - 10.8 x 109/L).The peripheral blood smear is represented in the photograph.Which of the following are the most likely associated conditions? | View Page |
| Hemolytic disease of the newborn Jaundice was recognized in a day-old infant. Notice particularly the size variation (anisocytosis) of the erythrocytes on the infant's peripheral smear. What does this observation mean? Does it provide immediate information that might serve as guidance in expediting diagnosis and treatment? Note that normal-sized red blood cells, microcytes, microspherocytes, macrocytes, and nucleated red blood cells are all present. Red cell variations are expected findings in healthy neonates, but the variations here are exaggerated. Hyposplenic functional features may appear, including acanthocytes, spherocytes, and possibly Howell-Jolly bodies, especially if hemolysis is particularly vigorous. A high (3-7%) reticulocyte count is not unusual during the first three or four days after birth, however, the marrow in this jaundiced infant is proliferating vigorously in response to hemolysis. A call for more red cells is urgent. Immature red cells (in the form of nucleated red cells) and red cells with stippling of RNA (basophilic stippling) are readily identified. Red cell maturation sequence has not been totally processed in the marrow nor is all residual red cell debris removed by the spleen. In the lower photograph are reticulocytes stained by supravital stain (new methylene blue). Basophilic stippling (specks of RNA) stains with both supravital stains and with routine Wright-Giemsa stain. | 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 |
| Warm antibody hemolytic disease A 49-year-old male with pneumonia was treated with penicillin. He became jaundiced with yellow sclera. Observe the photograph of his peripheral blood smear. Anisocytosis was observed with pale-centered microcytes and polychromatophilic macrocytes. Since penicillin is a classic offender for autoimmune hemolytic disease, the clinician asked for an antihuman globulin (AHG) test, also known as the Coombs test. A positive AHG reaction occurs when the antibody stimulated by penicillin becomes attached to red blood cells. Hemolysis follows, leaving the patient with jaundice and a peripheral blood smear, as demonstrated in the photograph. | View Page |
| The arrangement of the erythrocytes in this peripheral smear should be reported out as rouleaux formation. | View Page |
| Dimorphic RBC population Illustrated in the photomicrograph of a peripheral smear are two populations of erythrocytes. Approximately 50% of the erythrocytes are normal size and contain a full complement of hemoglobin. The patient had received blood transfusions. The transfused red blood cells are the normocytic, normochromic red cells. Admixed are microcytic erythrocytes and larger erythrocytes, some faintly mottled or smudged, suggestive of reticulocytes. This picture represents a hemolytic process with a reticulocyte response. A similar dimorphic red cell population appears following erythropoietin therapy. It is important to recognize when a population of cells in the peripheral smear is not in context with anticipated laboratory findings and the clinical situation. | View Page |
| Microcyte with Normal Hemoglobin Content A microcyte with normal hemoglobin content (one-third of central pallor) can be seen in the center of this field, just below and to the left of the lymphocyte. Since many of the other cells in this field are normal or larger than normal, the MCV would be within the normal range although the diameter and volume of this individual cell would be lower than normal. This type of microcyte can be seen in some hemolytic anemias and the rare enzyme deficiency, pyruvate kinase deficiency anemia. | View Page |
| Which of the following characteristics can be seen in the microcytes present in some hemolytic disorders? | View Page |
| Another Example of Microcytes Another example of microcytes seen in a slide from a patient with hemolytic anemia. Compare the two microcytes in the center of the field with the lymphocyte to the right. Notice the larger red cell just below the microcytes is about the same size as the lymphocyte. Several other microcytes can also be seen in this field. | View Page |
| Another Knizocyte Another example of a knizocyte is seen in this slide. These forms are seen in conditions in which spherocytes are visible and in some types of hemolytic anemia. | View Page |
| Conditions Associated with Sherocytes Examples of conditions in which spherocytes can be seen include hereditary spherocytosis and immune hemolytic anemias (i.e., ABO incompatibility). Spherocytes can also form in conditions where there has been a direct physical or chemical injury to the cells, such as heat. An example would be a smear from an individual who has suffered severe burns. In each of the above conditions, tiny bits of membrane are removed from the adult red cells, leaving the cell with a decreased surface/volume ratio. In hereditary spherocytosis where spherocytes are numerous, the MCHC value will be at the upper limits of normal, or about 36. The identification of spherocytes on the smear of a patient with hereditary spherocytosis can aid significantly in the diagnosis of the disorder. In vitro conditions which will cause spherocytes include prolonged storage, i.e. stored bank blood. | View Page |
| Another Keratocyte Another example of a helmet cell is seen in the center of this field. Examples of conditions in which keratocytes can be seen include intravascular coagulation, microangiopathic hemolytic anemia, glomerulonephritis, and rejection of renal transplants. The diagnosis of these disorders is not based on the presence of keratocytes. | View Page |
| The upper photograph of a bone marrow section reveals distinct hyperplasia with total replacement of marrow fat. A bone marrow smear stained with Wright/Giemsa is displayed in the lower photograph. Calculate the M:E ratio between myeloid and erythroid cells found in the lower photograph. The total peripheral blood white blood cell count was 5,400/cumm. This bone marrow architecture may be found in each of the following conditions except: | View Page |
| The upper photograph of this bone marrow section also reveals distinct hyperplasia with total replacement of the fat. The lower photograph is a Wright/Giemsa stain. Calculate the M:E ratio of the distribution of myeloid and erythroid cells in the lower photograph. The peripheral white blood count was 18,500/cumm. The most likely associated condition is: | View Page |
| The peripheral blood smear tagged in the photograph was held for review because of too many platelets, about double the normal average of 8 - 15/oil immersion field or one per 10 - 20 RBC's. Conditions in which platelets are increased as noted in the photograph include: | View Page |
| Erythrophagocytosis Illustrated in the photograph is a phagocyte devouring several erythrocytes.This uncommon phenomenon occurs in the bone marrow and in the spleen as part of the process of erythrocyte destruction. Erythrophagocytosis is found in histological sections of the spleen in cases of hemolytic anemia.This phenomenon appears also in splenic sections in lupus erythematosis, and in rheumatoid arthritis.Our example is from a patient with a myeloproliferative disorder and is a rare example of a circulating erythrophagocytic cell in the peripheral blood. | View Page |