SUCCESS! In Clinical Laboratory Science: Hematology - Erythrocyte Disorders Pt 3

B. Iron stores are depleted B. When iron use exceeds absorption, iron stores (serum ferritin) are depleted first. At this early stage, there is no anemia (normal hemoglobin) and the transferrin level is normal. This is followed by increased transferrin synthesis (TIBC) and decreased serum iron. Finally, a microcytic, hypochromic anemia develops

When iron use exceeds absorption, which of the following occurs first? A. Hemoglobin level decreases. B. Iron stores are depleted C. Transferrin synthesis increases. D. Excretion of iron decreases.

C. Increased serum transferrin, decreased transferrin saturation, decreased ferritin C. Low serum iron and iron stores (represented by serum ferritin) characterize iron deficiency that is severe enough to result in anemia. The production of transferrin, the iron transport protein, increases as iron stores decrease. Transferrin saturation decreases dramatically so that transferrin is less than 15% saturated with iron.

Which of the following characterizes iron deficiency anemia? A. Decreased serum iron, decreased transferrin saturation, normal ferritin B. Decreased serum transferrin, decreased transferrin saturation, decreased ferritin C. Increased serum transferrin, decreased transferrin saturation, decreased ferritin D. Increased serum transferrin, increased transferrin saturation, decreased serum iron

C. Chronic gastrointestinal blood loss C. The anemia of chronic disease (ACD) is very common and develops in patients with chronic infections (tuberculosis), chronic inflammatory disorders (rheumatoid arthritis, systemic lupus), and malignant disease (cancer, lymphoma). ACD has a complex etiology that includes impaired release of storage iron for erythropoiesis and a reduced response to erythropoietin. The anemia may be normocytic or microcytic, and severity depends on the underlying disorder.

Which of the following disorders is not commonly linked to the development of anemia of chronic disease? A. Persistent infections B. Noninfectious inflammatory disorders C. Chronic gastrointestinal blood loss D. Malignancy

D. The autoantibody is usually an IgG type directed against Rh antigens. D. Cold autoimmune hemolytic anemia (CAIHA), or cold hemagglutinin disease, is characterized by the production of IgM cold autoantibodies that often show I specificity. The cause of the autoantibody production may be unknown (primary) or occur secondary to Mycoplasma pneumonia or lymphoma. Significantly high liters can result in agglutination of red cells in the extremities called Raynaud's phenomenon (acrocyanosis).

Which of the following does not accurately describe cold autoimmune hemolytic anemia? A. Red cell agglutination in extremities induces Raynaud's phenomenon. B. It may occur secondary to Mycoplasma pneumonia. C. Hemolysis is complement-mediated or via removal of coated cells. D. The autoantibody is usually an IgG type directed against Rh antigens.

D. Folic acid deficiency D. Splenomegaly is a common finding in hemolytic anemias, because the spleen is the major site of extravascular red cell destruction. Patients with hereditary spherocytosis and hemoglobin SC disease often have enlarged spleens for this reason. Patients with beta-thalassemia major exhibit splenomegaly because of active splenic removal of red cells, but the spleen may also be a site of extramedullary erythropoiesis. Splenomegaly can also be due to extramedullary hematopoiesis in malignant disorders such as polycythemia vera or myelofibrosis. Splenomegaly would not be a characteristic finding in megaloblastic anemia.

In which of the following disorders would splenomegaly not be a common finding? A. Homozygous beta-thalassemia B. Hereditary spherocytosis C. Hemoglobin SC disease D. Folic acid deficiency

A. Release of merozoites from erythrocytes A. The hemolytic crisis of malaria results from the rupture of erythrocytes containing merozoites. This event becomes synchronized to produce the fever and chill cycles that are characteristic of this infection. In severe infections, particularly those caused by Plasmodium falciparum, the massive intravascular hemolysis results in significant hemoglobinuria.

The hemolysis associated with infection by malaria organisms is due to the A. Release of merozoites from erythrocytes B. Invasion of erythrocytes by merozoites C. Host's immunologic response to infected erythrocytes D. Toxins produced by the malarial organism

A. Impaired release of storage iron because of increased hepcidin levels A. In the anemia of chronic disease (ACD), a chronic illness causes impaired release of iron from storage. These patients have iron but are unable to use it for bone marrow erythropoiesis. Hepcidin, a hormone produced by the liver, plays a major role in the regulation of body iron by influencing intestinal absorption and release of storage iron from macrophages. Hepcidin levels increase during inflammation (positive acutephase reactant), which causes decreased release of iron from stores. There is also impaired response of marrow red cell precursors to erythropoietin stimulation in ACD. The impaired response is thought to be related to the effects of inflammatory cytokines. Recombinant erythropoietin improves the anemia in some cases.

The major mechanism responsible for the anemia of chronic disease is A. Impaired release of storage iron because of increased hepcidin levels B. Damaged bone marrow stem cells C. Immune destruction caused by red cell autoantibodies D. Increased erythropoietin response by committed red cell progenitor cells

B. Result of hyperplastic marrow activity B. The demand for red blood cell replacement in beta-thalassemia major during early childhood development results in a hyperproliferative marrow. Expansion of the marrow causes the bones to be thin and narrow. This may result in pathologic fractures. Facial bones have the Mongoloid appearance, with prominence of the forehead, cheekbones, and upper jaw.

Thinning of bones and deformation of facial bone structure seen in homozygous beta-thalassemia is a A. Consequence of disturbances in calcium metabolism B. Result of hyperplastic marrow activity C. Secondary disorder due to immunologic response D. Result of increased fibroclast activity

D. Crenated cells caused by incorrect blood to anticoagulant ratio D. The incorrect ratio of blood to anticoagulant caused the cells to shrink. This produced the crenated appearance of the red cells. This is an artifact as opposed to a significant clinical finding and can also be the result of prolonged blood anticoagulation. Spur cells (or acanthocytes) lack a central pallor area and have sharp projections, as opposed to crenated cells (or echinocytes), which have a pallor area and blunt projections.

A clinical laboratory scientist received a 5 mL EDTA tube that contained 0.5 mL of anticoagulated blood. A smear was prepared and stained with Wright's stain. When examined microscopically, the majority of cells appeared to have many evenly distributed, blunt spicules on the surface. How should this cellular appearance be interpreted? A. An anemic condition requiring further testing B. Spur cells caused by using incorrect technique during slide preparation C. Artifact caused by a dirty spreader slide D. Crenated cells caused by incorrect blood to anticoagulant ratio

A. Pyruvate kinase deficiency A. Pyruvate kinase (PK) is an enzyme of the Embden-Meyerhof pathway (anaerobic glycolysis). A deficiency of PK results in decreased ATP generation, which causes impairment of the cation pump and a loss of normal membrane deformability. PK-deficient cells have a shortened survival time, but clinical manifestations vary widely.

A failure to generate sufficient ATP is characteristic of red blood cells with A. Pyruvate kinase deficiency B. Glucose-6-phosphate dehydrogenase deficiency C. Lipoprotein deficiency D. Hexokinase deficiency

C. Bone marrow erythroid precursors exhibit normoblastic maturation. C. Intrinsic factor is a glycoprotein secreted by the parietal cells, along with HC1, that is needed to bind vitamin B12 for absorption. Pernicious anemia (PA), which is a megaloblastic anemia caused by the lack of intrinsic factor, is most common cause of vitamin B12 deficiency (cobalamin). PA is characterized by atrophy of the gastric parietal cells and achlorhydria (absence of HC1). Autoimmune factors are involved because a high percentage of patients produce autoantibodies to intrinsic factor (50%) and/or parietal cells (90%). The bone marrow erythroid precursors exhibit megaloblastic maturation, with nuclear maturation lagging behind cytoplasmic maturation (asynchrony is also seen in developing granulocytes and platelets). Many fragile red cells die in the bone maiTow, and those released into the circulation have a very short survival, which causes a marked increase in lactate dehydrogenase levels.

A moderately anemic patient with suspected pernicious anemia (PA) shows intrinsic factor antibodies and a low cobalamin level. Which of the following would not support the diagnosis of PA? A. Gastric atrophy and achlorhydria B. Oval macrocytes and Howell-Jolly bodies C. Bone marrow erythroid precursors exhibit normoblastic maturation. D. Elevated serum lactate dehydrogenase (LD) and bilirubin levels

D. By 6 months of age D. The switch from gamma-globin chain production for Hb F to beta-globin chain synthesis for Hb A occurs 3-6 months after birth. Clinical symptoms of a homozygous beta-globin chain defect, such as sickle cell disease or homozygous beta-thalassemia, will not be evident until about 6 months of age or shortly after. Alphaglobin chain production is normally high throughout fetal and adult life. A homozygous defect involving the alpha-globin chain will affect the infant in utero.

Clinical manifestations of a homozygous mutation involving the beta-globin gene will most likely appear A. During embryonic development B. In the neonate at birth C. No later than 3 weeks after birth D. By 6 months of age

B. Hemoglobin D B. Hemoglobin D migrates in the same location as hemoglobin S on cellulose acetate at alkaline pH but does not cause sickling. The negative solubility test rules out the presence of hemoglobin S. Target cells are seen in large numbers in homozygous hemoglobin D disease. The quantification of 95% differentiates homozygous from heterozygous states where less than 50% hemoglobin D would be seen.

A cellulose acetate electrophoresis revealed a large band of hemoglobin in the hemoglobin S position. This band quantified at 95%. The peripheral smear revealed 70% target cells, and the solubility test was negative. Based on this information, what is the hemoglobin? A. Hemoglobin C B. Hemoglobin D C. Hemoglobin E D. Hemoglobin S

B. Aplastic anemia B. Aplastic anemia is bone marrow failure characterized by hypocellularity and decreased production of all cell lines. The normal M:E ratio (4:1) does not change in aplasia, because the number of both myeloid and erythroid precursors is decreased. In anemias such as sickle cell anemia, beta-thalassemia major, or megaloblastic anemia, the marrow becomes hypercellular because of an increase in erythroid precursors, and the M:E ratio falls.

A bone marrow M:E ratio of 4:1 would bean expected finding for A. Sickle cell anemia B. Aplastic anemia C. Beta-thalassemia major D. Megaloblastic anemia

B. Glucose-6-phosphate dehydrogenase B. G6PD deficiency compromises the ability of the glutathione reduction pathway to prevent the oxidation of hemoglobin. Oxidative stress may occur from infections, ingestion of mothballs, ingestion of fava beans, and certain drugs, including primaquine or sulfonamides. The oxidized hemoglobin precipitates in the form of Heinz bodies, which leads to a hemolytic crisis characterized by intravascular red cell destruction, removal of Heinz bodies by splenic macrophages, and the presence of spherocytes and fragmented red cells on the smear.

A previously healthy man experiences weakness and hemoglobinuria after taking the antimalarial agent primaquine. This hemolytic attack most likely occurred because of a deficiency of A. Pyruvate kinase B. Glucose-6-phosphate dehydrogenase C. 2,3-Bisphosphoglycerate D. Methemoglobin reductase

B. Secondary warm autoimmune hemolytic anemia B. The immune hemolytic anemia indicated by the smear findings is warm autoimmune hemolytic anemia (WAIHA). Antibody-coated red cells are being partially phagocytized by macrophages (with receptors for IgG and complement), causing loss of membrane fragments. The spherocytes are ultimately destroyed, primarily in the spleen. The cause of the autoantibody production may be unknown (idiopathic), develop secondary to a disease that alters the immune response (chronic lymphocytic leukemia or lymphoma), or can be drug induced. Cold hemagglutinin disease is characterized by red cell agglutination due to a cold autoantibody.

An elderly man with a 10-year history of chronic lymphocytic leukemia presented with jaundice and fatigue that was attributed to a recent 3-gram drop in his hemoglobin. Many spherocytes and polychromatophilic red cells were found on his Wright's stained blood smear. Which type of immune hemolytic anemia is most likely? A. Idiopathic warm autoimmune hemolytic anemia B. Secondary warm autoimmune hemolytic anemia C. Primary cold hemagglutinin disease D. Paroxysmal cold hemoglobinuria

A. Renal tumors A. A need for the increased oxygen carrying capacity provided by additional red blood cells is found in conditions such as pulmonary disease, where normal oxygenation is inhibited. A decrease in the ability of the cardiovascular system to appropriately circulate cells is another reason for increased erythrocytes. Individuals with a high level of methemoglobin, such as heavy smokers or persons with genetic disorders, cannot effectively unload oxygen. This results in a need for increasing the number of red blood cells to compensate. Renal tumors are associated with excess production of erythropoietin, leading to an inappropriate polycythemia

An increase in erythropoietin is not a normal compensating mechanism in which of the following conditions? A. Renal tumors B. Heavy smoking C. Cardiovascular disease D. Pulmonary disease

B. Quantitative defect in globin-chain synthesis B. Thalassemias are a group of congenital disorders characterized by quantitative defects in globin-chain synthesis. Alpha-thalassemias result from gene deletions that cause a reduced rate of alpha-globin chain production. Beta-thalassemias result from point mutations that cause a reduced rate of beta-globin chain synthesis. Normally, equal amounts of alpha- and beta-globin chains are produced for Hb A synthesis. In alpha- or betathalassemias, synthesis of globin chains is imbalanced, because a decreased production rate of one type of globin chain causes an excess of the other (consequences will depend on the thalassemia type).

Thalassemias are the result of a A. Structural defect in the heme portion of hemoglobin B. Quantitative defect in globin-chain synthesis C. Qualitative defect in globin-chain structure D. Change in hemoglobin solubility properties

A. Loss of erythropoietin synthesis A. The anemia of chronic renal failure results from decreased production and release of erythropoietin from the diseased kidney. The drop in erythropoietin results in decreased red blood cell production by the marrow. Recombinant erythropoietin is of great value in treating anemia resulting from end-stage renal disease. Iron or folate supplements may be needed to maximize the response, especially in patients on dialysis. Uremic metabolites may cause reduced red cell survival and impairment of platelet function.

The anemia found in chronic renal failure is most likely caused by A. Loss of erythropoietin synthesis B. Lack of cellular oxygen demand C. Defective iron absorption D. Destruction of red cells by uremic metabolites

B. Macrocytic anemia B. The fish tapeworm competes for vitamin B12, and a macrocytic (megaloblastic) anemia may develop. Hookworm infestation causes chronic blood loss and a microcytic anemia due to iron deficiency. A variety of organisms are associated with hemolysis, including malaria and clostridial infections. Viral hepatitis can cause marrow suppression and a normocytic, hypoproliferative anemia.

The fish tapeworm Diphyllobothrium latum is associated with the development of A. Microcytic anemia B. Macrocytic anemia C. Hemolytic anemia D. Hypoproliferative anemia

B. Paroxysmal nocturnal hemoglobinuria B. Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired defect of membrane structure in which red cells have a high affinity for complement binding. PNH is characterized by pancytopenia and chronic intravascular hemolysis with hemoglobinuria and hemosiderinuria. A stem cell mutation causes production of red cells, white cells, and platelets that are sensitive to complement lysis because of the loss of a membrane glycolipid (GPI). The sucrose hemolysis test can be used to screen for PNH red cells, but the Ham's acid serum test has been replaced by immunophenotyping for confirmation of PNH. Paroxysmal cold hemoglobinuria (PCH) is characterized by intravascular hemolysis and hemoglobinuria after cold exposure that is due to a complement-binding autoantibody. A transient finding of hemoglobinuria following forceful contact of the body with hard surfaces (as may be seen in joggers and soldiers) describes March hemoglobinuria.

Which of the following is an acquired red cell membrane defect that results in increased sensitivity to complement binding? A. March hemoglobinuria B. Paroxysmal nocturnal hemoglobinuria C. Paroxysmal cold hemoglobinuria D. Methemoglobinemia

D. Increased sickling occludes vessels. D. Red cells that contain a high concentration of hemoglobin S will assume the sickle shape when deprived of oxygen (which can be reversed if reoxygenated). After repeated sickling, reversion capabilities are lost and irreversibly sickled cells (ISCs) are seen. Sickle cells are mechanically brittle, nondeformable cells that become impeded in circulation, causing blocks that restrict blood flow in vessels and leading to organs (vascular occlusive disease). They are easily trapped in the small vessels of the spleen, leading to obstructive ischemia and eventual destruction of splenic tissue

Which of the following is associated with sickle cells? A. Increased oxygen tension promotes sickling. B. There is decreased mechanical fragility. C. There is increased deformability. D. Increased sickling occludes vessels.

C. Reversible with intramuscular vitamin B12 injections C. In the idiopathic or primary type of sideroblastic anemia, the blocks in the protoporphyrin pathway (heme synthesis) that lead to iron overload are unknown and, therefore, are irreversible. The anemia is refractory (unresponsive) to treatment other than transfusion. Ringed sideroblasts and increased stainable iron will be found in the bone marrow when stained with Prussian blue. This primary, acquired form of sideroblastic anemia is also known as refractory anemia with ringed sideroblasts (RARS) and is classified as a myelodysplastic syndrome.

Which of the following is not a characteristic of the idiopathic type of sideroblastic anemia? A. Refractory to treatment B. Blocks in heme synthesis are unknown C. Reversible with intramuscular vitamin B12 injections D. Subtype of myelodysplastic syndromes

A. Methotrexate therapy A. Secondary, acquired sideroblastic anemia is the result of blocks in the protoporphyrin pathway that can be identified and, therefore, are reversible if the toxin or agent is removed. Alcohol inhibits vitamin B6 and anti-tuberculosis drugs also interfere with vitamin B6 (pyridoxine). Lead poisoning causes multiple blocks in protoporphyrin synthesis, including inhibition of ferrochelatase, which is needed for iron incorporation into protoporphyrin to produce heme. Methotrexate is an antifolate chemotherapeutic agent that causes a drug induced megaloblastic anemia.

Which of the following is not associated with acquired reversible sideroblastic anemias? A. Methotrexate therapy B. Lead intoxication C. Isoniazid treatment for tuberculosis D. Acute alcohol ingestion

D. Reduced red cell survival D. Aplastic anemia is a stem cell defect that leads to decreased production of erythrocytes, leukocytes, and platelets (pancytopenia). The survival of red cells released into the circulation is normal. Infection is a serious problem because of the lack of neutrophils. The reduced number of platelets is responsible for the bleeding often seen. Treatment includes blood and platelet transfusions, antibiotics, growth factors, and steroids. Bone marrow transplantation may be necessary.

Which of the following phrases about aplastic anemia is false? A. Stem cell disorder B. Risk of life-threatening infection C. Frequent bleeding complications D. Reduced red cell survival

A. Sickle cell disease during crisis A. The red blood cell distribution width (RDW) is an index of red cell size variation or anisocytosis. The RDW will be high when a heterogeneous cell population consisting of red cells with varying sizes is present (sickle cell anemia with compensation). The RDW is low when a homogeneous or single population of red cells is present that are of uniform size (thalassemia minor, anemia of chronic disease).

Which of the following represents an anemia that would have a high red cell distribution width (RDW)? A. Sickle cell disease during crisis B. Thalassemia minor C. Aplastic anemia D. Anemia of chronic disorders

A. Electrophoresis shows approximately 60% hemoglobin A and 40% hemoglobin C A. Hemoglobin C disease results from a homozygous substitution of lysine for glutamicacid at position 6 of the beta-globin chains. Numerous target cells and occasional intracellular C crystals will be found on the blood smear. Osmotic fragility is decreased (increased resistance) because of the many target cells, and electrophoresis will show an absence of Hb A and over 90% Hb C. The clinical severity of Hb CC is mild as compared to Hb SS or Hb SC diseases.

Which of the following statements about hemoglobin C disease is false? A. Electrophoresis shows approximately 60% hemoglobin A and 40% hemoglobin C. B. Target cells are frequently seen on peripheral smears. C. Red cells may contain bar-shaped intracellular crystals. D. The disorder is less severe than sickle cell disease.

A. It is due to a reduction in the number of erythrocytes. A. Although iron deficiency may be the most common cause of anemia in pregnancy, there is a mild form of anemia that develops during the third trimester in pregnant women with adequate iron levels. Although both erythrocytes and plasma increase during pregnancy, the plasma increases in a higher proportion, causing a relative (pseudo) anemia. This increased blood volume actually increases oxygen delivery to both the mother and the fetus.

Which of the following statements about the relative anemia of pregnancy is false? A. It is due to a reduction in the number of erythrocytes. B. It is normocytic and normochromic. C. It does not produce an oxygen deficit for the fetus. D. It is associated with an increase in plasma volume.