SUCCESS! In Clinical Laboratory Science: Hematology - Erythrocyte Disorders Pt 1

C. Hemoglobin SC disease C. As seen in Color Plate 5, the presence of numerous target cells and SC crystals on the peripheral blood smear suggests the presence of hemoglobin SC disease. These bizarre crystals are distinguished by one or more blunt, fingerlike projections that protrude from the cell membrane. Clinically, hemoglobin SC disease is not usually as severe as sickle cell disease, and electrophoresis shows equal amounts of Hb S and Hb C. Codocytes, in varying numbers, are typical of hemoglobin S, C, and E disorders.

A 14-year-old African-American male was seen in the clinic for abdominal pain. A complete blood count revealed the following: WBC 7.0 X 1 09/L (7.0 X 1 03/|JLL) RBC 2.90 X 1 01 2/L (2.90 X 1 06/(JiL) Hemoglobin 85 g/L (8.5 g/dL) Hematocrit 0.25 L/L (25%) MCV 86.2 f L MCH 29.3 pg MCHC 340 g/L (34.0 g/dL) ROW 21% The peripheral smear showed the red blood cell morphology seen in Color Plate 5. What condition is suggested by these findings? A. Hemoglobin E disease B. Hemoglobin S disease C. Hemoglobin SC disease D. Hemoglobin C disease

B. Cooley beta-thalassemia major B. Cooley anemia, or beta-thalassemia major, would be the appropriate diagnosis in this case. In this condition, two beta-thalassemia genes are inherited that result in virtually no hemoglobin A production because no beta-globin chains are produced. The primary hemoglobin made is hemoglobin F. The severe microcytic anemia results from the destruction of red cell precursors in the bone marrow (ineffective erythropoiesis) and rigid red cells in the blood that contain unused alpha-globin chains. Nucleated red blood cells and target cells, as seen in Color Plate 4B, are common, as well as basophilic stippling. Infants with alpha-thalassemia major die in utero or shortly after birth. Hemoglobin H disease (three-gene deletion alpha-thalassemia) results from deficient, alpha-chain synthesis that leads to production of Hb H (four beta chains), an unstable hemoglobin that forms Heinz bodies and causes chronic hemolysis. No clinical manifestations are seen in patients with hereditary persistence of fetal hemoglobin (HPFH).

A 9-month-old male was seen in the Emergency Department with a femur fracture that had occurred from a fall down the stairs. Upon physical examination, the physician noted hepatosplenomegaly, extreme pallor, and a slight arrhythmia. A complete blood count revealed the following: WBC 12.2 X 1 09/L (1 2.2 X 1 03/(uL) RBC 3.05 X 1 01 2/L (3.05 X 1 06/(uL) Hemoglobin 61 g/L (6.1 g/dL) Hematocrit 0.20 L/L (20%) MCV 65.5 fL MCH 20 pg MCHC 305 g/L (30.5 g/dL) RDW 25% The Wright's stained blood smear showed the findings seen in Color Plate 4. Hemoglobin electrophoresis was ordered with results as follows: HgbA 0% HgbA2 3% HgbF 97% Which condition is most likely causing the hematologic abnormalities? A. Alpha-thalassemia major B. Cooley beta-thalassemia major C. Hemoglobin H disease D. Hereditary persistence of hemoglobin F

B. Four gamma chains B. In infants with homozygous alphathalassemia, no alpha-globin chains are produced (because of the deletion of all four alpha genes). Consequently, the infants have nearly 100% hemoglobin Bart's, which consists of four gamma-globin chains. This hemoglobin migrates farther toward the anode than Hb A. Because Hb Bart's has a very high oxygen affinity, it is useless for delivery of oxygen to the tissues, making its presence incompatible with life. Hemoglobin H, composed of four beta chains, also migrates farther than Hb A, but Hb H disease is not fatal

A cellulose acetate hemoglobin electrophoresis (alkaline pH), performed on the blood of a stillborn infant, revealed a single band that migrated farther toward the anode than did the Hb A control. What is the most likely composition of the stillborn infant's hemoglobin? A. Four beta chains B. Four gamma chains C. Two alpha and two beta chains D. Two alpha and two gamma chains

C. Myelophthisic C. Myelophthisic anemia is an anemia of bone marrow failure. It is seen in patients who are experiencing bone marrow replacement of normal hematopoietic tissue by metastatic cancer cells, fibrosis, or leukemia. The anemia is considered a hypoproliferative anemia because there is no hemolysis involved and the cells are normocytic, normochromic. Disruption of the bone marrow by abnormal cells can result in the release of immature cells (nucleated red cells and immature neutrophils) into the blood and may involve blood cell production in extramedullary sites

A patient with normocytic, normochromic anemia secondary to small cell carcinoma may be exhibiting an anemia designated as A. Hemolytic B. Megaloblastic C. Myelophthisic D. Sideroblastic

C. An intrinsic hereditary defect of red cells should be suspected. C. The peripheral blood as seen in Color Plate 3 shows numerous elliptocytes (ovalocytes). If they were artifact due to smear preparation, they would be oriented in the same direction. Hereditary elliptocytosis (HE) is associated with symptomatic hemolytic anemia in only about 10-15% of the cases, but the presence of an enlarged spleen is evidence of ongoing extravascular destruction. In patients with chronic hemolysis, gallstones are a common complication because of excess bilirubin catabolism. In most persons with HE, anemia does not develop because bone marrow production of red cells compensates for the mild shortening of red cell life span.

Color Plate 3 shows the peripheral blood of a 16-year-old female with a sporadic history of dizzy spells, fainting, and jaundice. This patient also had a history of periodic abdominal pain related to gallstones. Upon physical examination, she exhibited mild splenomegaly. Her hemoglobin was 107 g/L (10.7 g/dL), hematocrit was 0.32 L/L (32%), red cell indices were normal, and the direct antiglobulin test was negative. Based on history and peripheral blood morphology, which of the following statements is most likely true ? A. Hemoglobin S will be revealed by electrophoresis. B. Tests to confirm iron deficiency should be ordered. C. An intrinsic hereditary defect of red cells should be suspected. D. The anemia is secondary to spleen and gallbladder disorders.

B. Membrane cation permeability B. The major defect in hereditary stomatocytosis is altered permeability of the red cell membrane to Na+ and K+ ions. A net gain of sodium within the cell leads to increased water entry and the appearance of a swollen cell with a slit-like area of pallor. This is a heterogeneous group of disorders, in that a number of specific membrane defects have been postulated, and anemia varies from mild to severe. One autosomal dominant disorder is associated with Rh-null individuals.

Hereditary stomatocytosis is manifested physiologically by changes in A. Hemoglobin oxygen affinity B. Membrane cation permeability C. Efficiency of hemoglobin reduction D. Glycolytic ATP production

A. Has no identifiable cause A. Any idiopathic disorder is one for which there is no apparent cause. Ionizing radiation is a well-known cause of aplasia, as is chemical exposure (pesticides, benzene). latrogenic disorders are those that result from treatments for a different disorder; for example, aplasia can result from chloramphenicol treatment for bacterial disease. Aplastic anemia may develop as a complication from infections such as EpsteinBarr or hepatitis viruses.

Idiopathic aplastic anemia is best defined as a form of anemia that A. Has no identifiable cause B. Is caused by a physician's treatment C. Follows exposure to ionizing radiation D. Develops after a viral infection

D. Megaloblastic anemia D. Deficiencies of folic acid (folate) and vitamin B12 result in abnormal DNA synthesis and a resultant delay in nuclear maturation in comparison to cytoplasmic development. These anemias are categorized as megaloblastic because of the giant red cell precursors observed in the bone marrow. The other anemias are characterized by defects of heme (sideroblastic anemia and iron-deficiency anemia) or globin synthesis (hemoglobin C disease).

Impaired DNA metabolism is characteristic of A. Hemoglobin C disease B. Iron-deficiency anemia C. Sideroblastic anemia D. Megaloblastic anemia

D. Increased platelets, increased granulocytes, decreased erythropoietin level D. Polycythemia vera (PV) belongs to the group of disorders that are hematopoietic stem cell defects and commonly characterized as myeloproliferative disorders. Although the major increase in PV is in red blood cells, there is also an overproduction of granulocytes and platelets, particularly in the early stages of the disease. The increased production of red cells in PV is not due to the activity of erythropoietin. The production of erythropoietin is almost completely suppressed in this malignant condition.

In addition to an increase in red blood cells, which of the following is characteristic of polycythemia vera? A. Decreased platelets, decreased granulocytes, decreased erythropoietin level B. Decreased platelets, decreased granulocytes, increased erythropoietin level C. Increased platelets, increased granulocytes, increased erythropoietin level D. Increased platelets, increased granulocytes, decreased erythropoietin level

B. Glutamic acid replaces lysine on position 26 of the beta chains B. Hemoglobin nomenclature indicates a number of things. The symbol a2 or a2A indicates the presence of normal adult, or A, alpha chains. The designation (3226 Glu~>Lys indicates that lysine residues have replaced glutamic acid on position 26 of the beta chains. All types of E hemoglobin show a similar electrophoretic mobility and migrate closely to hemoglobins C and A2 on cellulose acetate (alkaline pH). Hemoglobin E occurs with the greatest frequency in Southeast Asia.

In regard to variant hemoglobin E, alpha 2 Beta 2 26 Glu -> Lys, which of the following statements is false? A. There are two normal alpha chains. B. Glutamic acid replaces lysine on position 26 of the beta chains. C. Hemoglobin E is the second most common hemoglobin variant known. D. Glutamic acid is normally found at position 26 of the beta chain.

B. Dietary insufficiency B. Folate deficiency is most commonly a result of poor dietary intake of folate alone or in combination with increased requirements as during pregnancy. Daily requirements for folate are high, and depletion of folate stores can occur within 4 months as compared to vitamin B12, in which deficiency takes at least 2 years to develop (there are high stores). Thus, dietary deficiency of vitamin B12 is rare, but folate supplements are commonly required during pregnancy or in hemolytic anemias with excess cell turnover.

Of the following, the leading cause of folate deficiency is A. Increased requirements B. Dietary insufficiency C. Drug inhibition D. Malabsorption

C. Iron deficiency C. Pica is a clinical finding seen in some patients with iron deficiency. Pica is unusual cravings for nonfood items that may include dirt, clay, laundry starch, or, most commonly, ice. Among some cultures, pica is a custom (eating dirt) that may contribute to iron deficiency. In children, lead poisoning often results from the ingestion of dirt or lead-based paint from toys and may be related to iron deficiency. Porphyrias are a group of inherited disorders characterized by enzyme deficiencies and abnormal porphyrin metabolism. The presence of pyridoxine (pyridoxal-5'-phosphate or vitamin Bg) is important to early porphyrin synthesis.

Pica is most commonly associated with which of the following conditions? A. Pyridoxine deficiency B. Lack of erythrocyte folate C. Iron deficiency D. Porphyrias

D. No further testing is indicated D. Elevated RBC, hemoglobin, and hematocrit values in a newborn are a carryover from intrauterine life, when a high number of red cells were needed to carry oxygen. Erythropoiesis is suppressed in response to the marked increase in oxygenation of tissues after birth, and the reticulocyte count, which is initially high, will fall along with a slow decline in the hemoglobin level. A hemoglobin value below 140 g/L (14.0 g/dL) is abnormal for a neonate. Newborn red cells are macrocytic and up to 10 nucleated red cells per differential may be seen.

Results from a 1-day-old infant include a hemoglobin of 201 g/L (20.1 g/dL), hematocrit of 0.60 L/L (60.0%), MCV of 110.2 fL, and 4 nucleated red cells/100 WBCs. How should these results be interpreted? A. The elevated hemoglobin and hematocrit values indicate possible dehydration. B. The nucleated red cells suggest accelerated erythropoiesis due to a hemolytic process. C. Testing should be done to identify the cause of the macrocytosis. D. No further testing is indicated.

D. Idiopathic thrombocytopenic purpura (ITP) D. The schistocytes in Color Plate 6 are found in microangiopathic hemolytic anemia and caused by red cells shearing on fibrin strands deposited in small vessels. Widespread or localized (e.g., kidney) fibrin deposition in DIG, HUS, and TTP results in red cell fragmentation. In addition, thrombocytopenia is a usual feature of MAHA. ITP is characterized by severe thrombocytopenia that results from destruction of platelets by autoantibodies, but it is not associated with red cell damage or anemia.

The findings seen in Color Plate 6 can be found in patients with microangiopathic hemolytic anemia (MAHA). Which of the following conditions could not be responsible for this type of red cell destruction? A. Disseminated intravascular coagulation (DIC) B. Hemolytic uremic syndrome (HUS) C. Thrombotic thrombocytopenic purpura (TTP) D. Idiopathic thrombocytopenic purpura (ITP)

C. Hydrops fetalis C. Bart's hydrops fetalis (homozygous alphathalassemia major) is a lethal condition in which all normal hemoglobins are absent and the presence of Bart's hemoglobin results in death due to hypoxia. Severe cases of Rh hemolytic disease of the newborn/fetus (erythroblastosis fetalis) are characterized by hemolytic anemia, high numbers of nucleated red blood cells, and hyperbilirubinemia that can cause brain damage (kernicterus). The bilirubin level is elevated but anemia is mild, if present, in ABO hemolytic disease of the newborn.

The most likely cause of the stillborn infant's condition in question 83 is A. Erythroblastosis fetalis B. Rh hemolytic disease of the fetus C. Hydrops fetalis D. ABO hemolytic disease of the newborn

A. Both normal A. Because red blood cells and plasma are lost together, the hemoglobin and hematocrit will not reflect the severity of an acute hemorrhage until the lost blood volume begins to be replaced by the formation of plasma. The restoration of a normal blood volume is usually complete by 24 hours. It is then that the hemoglobin and hematocrit will reach their lowest point and will begin to rise only with the release of newly formed red cells, usually within 3-4 days.

What values would you expect to obtain on hemoglobin and hematocrit determinations done immediately after a major hemorrhage, if hemoglobin and hematocrit values were normal prior to the hemorrhage? A. Both normal B. Both decreased C. Hemoglobin decreased, hematocrit normal D. Hemoglobin normal, hematocrit decreased

D. Dacryocytes; myelofibrosis D. The red blood cells with single elongated projections, seen in Color Plate 7, are dacryocytes or teardrops. Dacryocytes are often seen in disorders of marrow replacement that affect bone marrow architecture, especially myelofibrosis. Teardrops can also result from the splenic removal of inclusions and may be present in a variety of anemias. Drepanocytes or sickle cells are observed during a sickling crisis of sickle cell anemia. Acanthocytes, echinocytes, and/or codocytes can be found in liver disease (presence varies with disease severity).

When viewing Color Plate 7, the red blood cells with a single elongated projection are known as and may be seen in A. Acanthocytes; liver disease B. Echinocytes; liver disease C. Drepanocytes; myelofibrosis D. Dacryocytes; myelofibrosis

C. Increased total iron-binding capacity C. Ringed sideroblasts result from the accumulation of iron deposits in the mitochondria surrounding the nucleus of erythroid precursors. The deposits are secondary to a defect in heme synthesis and a pathological finding in sideroblastic anemia. Blocks in the protoporphyrin pathway required for heme synthesis may be hereditary (rare) or acquired and result in iron overload with increased marrow iron. Pappenheimer bodies and basophilic stippling are frequent findings on the blood smear, and increased serum iron, decreased TIBC, increased percent transferrin saturation, and increased serum ferritin are usual.

Which of the following blood findings does not correlate with the presence of ringed sideroblasts in the bone marrow? A. Pappenheimer bodies B. Basophilic stippling C. Increased total iron-binding capacity D. Increased percent transferrin saturation

D. Pernicious anemia D. Reticulocytosis is indicative of increased erythropoietic activity by the bone marrow. This is a normal response in conditions involving premature red cell destruction in the circulation or following blood loss due to acute hemorrhage. The reticulocyte count is consistently increased in active hemolytic disease because the marrow speeds up red cell production to supply replacement cells. Anemia develops when the rate of red cell destruction exceeds the marrow's ability to replace red cells (uncompensated hemolytic disease). The reticulocyte count is not usually elevated in pernicious anemia even though increased marrow erythropoiesis occurs. The defective cellular maturation that occurs in megaloblastic anemias results in the death of many red cells in the bone marrow (ineffective erythropoiesis).

Which of the following conditions is not usually associated with marked reticulocytosis? A. Four days after a major hemorrhage B. Drug-induced autoimmune hemolytic anemia C. Sickle cell anemia D. Pernicious anemia

B. Folic acid and vitamin B12 deficiencies B. The blood profile alone cannot distinguish folic acid and vitamin B12 deficiencies, because both are characterized by macrocytic ovalocytes, Howell-Jolly bodies, and hypersegmented neutrophils. Clinical severity generally differentiates the heterozygous (mild) and homozygous (severe) conditions of thalassemic and sickle cell syndromes. The anemia of acute blood loss is usually normocytic, whereas the anemia of chronic blood loss becomes microcytic due to the development of iron deficiency.

Which of the following conditions show similar CBC and blood smear findings? A. Beta-thalassemia major and minor B. Folic acid and vitamin B12 deficiencies C. Acute and chronic blood loss D. Sickle cell disease and trait

C. Diamond-Blackfan anemia C. Diamond-Blackfan anemia is a congenital disorder that depresses only red blood cell production. Fanconi anemia is a congenital form of aplastic anemia that results in aplasia of all cell lines and has a high risk of developing acute myeloid leukemia or other cancers. The bone marrow distinguishes Diamond-Blackfan from the hypocellular marrow seen in aplastic anemia because there is a lack of erythroid precursors but a normal number of myeloid and megakaryocytic precursor cells.

Which of the following is a true red blood cell aplasia? A. Marrow replacement anemia B. Fanconi anemia C. Diamond-Blackfan anemia D. Donath-Landsteiner anemia

A. G6PD gene is located on the X chromosome. A. G6PD deficiency has a sex-linked inheritance pattern and is the most common enzyme deficiency in the hexose monophosphate (HMP) shunt. Individuals are asymptomatic unless exposed to oxidants, which compromise the ability of the glutathione reduction pathway to prevent the oxidation of hemoglobin. The oxidized hemoglobin precipitates in the form of Heinz bodies, which cause acute intravascular hemolysis. In the most common G6PD variant, the hemolytic episode is self-limiting, with old red cells that lack enzyme being destroyed and young red cells with some enzyme activity unaffected.

Which of the following is associated with glucose-6-phosphate dehydrogenase (G6PD) deficiency? A. G6PD gene is located on the X chromosome. B. Ongoing intravascular hemolysis occurs. C. All circulating red cells, including reticulocytes, lack enzyme activity. D. Splenectomy can relieve the rate of red cell destruction.

C. Dehydration secondary to diuretic use C. Dehydration is a cause of relative (pseudo) erythrocytosis due to plasma loss. High altitude adjustment, cardiac or pulmonary disease, and defective oxygen transport are all causes of absolute secondary erythrocytosis. Secondary erythrocytosis (polycythemia) is a compensatory increase in red cells, produced in an attempt to increase the amount of oxygen available to the tissues.

Which of the following is not a cause of absolute secondary erythrocytosis? A. Defective cardiac or pulmonary function B. High-altitude adjustment C. Dehydration secondary to diuretic use D. Hemoglobins with increased oxygen affinity

A. Extramedullary hematopoiesis A. Aplastic anemia can be defined as blood pancytopenia resulting from bone marrow failure. This stem cell disorder results in a hypocellular marrow with few developing precursors and decreased production of all cell lines. The anemia is generally normocytic or slightly macrocytic with reticulocytopenia. The "defect" also affects resting hematopoietic cells in the liver and spleen, so extramedullary hematopoiesis does not occur to compensate for marrow failure

Which of the following is not characteristic of aplastic anemia? A. Extramedullary hematopoiesis B. Bone marrow hypoplasia C. Absolute reticulocytopenia D. Blood findings of pancytopenia

C. Hemoglobin S is more soluble in dithionite than is normal hemoglobin. C. The hemoglobin solubility test can detect the presence of hemoglobin S, which is insoluble in the dithionite reagent, whereas normal hemoglobin A is soluble. A positive screening test, however, does not distinguish between patients with hemoglobin AS trait, hemoglobin SC disease, and hemoglobin SS disease, so results must be confirmed by electrophoresis. Sickle cell trait is clinically asymptomatic with target cells only. Disorders prevalent in the malarial belt (sickle cell trait, G6PD deficiency, hereditary ovalocytosis, thalassemia minor) are thought to impart resistance to falciparum malaria. Repeated splenic infarctions by sickle cell masses in hemoglobin SS disease cause autosplenectomy by adulthood

Which of the following statements about sickle cell syndromes is false? A. Asplenism may result from repeated sickling crises in the homozygous state. B. Heterozygous persons may be partly protected from infection by falciparum malaria. C. Hemoglobin S is more soluble in dithionite than is normal hemoglobin. D. Trait conditions are generally asymptomatic with no sickle cell formation.