Anemias and anti anemia drugs

Correct answer is reduced erythropoiesis from parvovirus infection. Patients with hereditary spherocytosis may have an aplastic crisis precipitated by a parvovirus infection. In adults who do not have a defect in normal RBC production, such as hereditary spherocytosis or sickle cell anemia, or who are not immunosuppressed, parvovirus infection is self-limited and often goes unnoticed. When there is an underlying RBC production defect, then RBC production is shut down by parvovirus, and there is no reticulocytosis. Disseminated intravascular coagulation gives rise to thrombocytopenia, bleeding, and the appearance of fragmented RBCs in the blood smear. Reticulocytosis would be prominent with hemolysis and with RBC antibodies. Iron deficiency does not occur in hemolytic anemias because the iron that is released from hemolyzed cells is reused.

Question 2 1 / 1 pts An 18-year-old woman from Copenhagen, Denmark, has had malaise and a low-grade fever for the past week, along with arthralgias. On physical examination, she appears very pale, except for a bright red malar facial rash. She has a history of chronic anemia, and spherocytes are observed on a peripheral blood smear. Her hematocrit, which normally ranges from 35% to 38%, is now 28%, and the reticulocyte count is very low. The serum bilirubin level is 0.9 mg/dL. Which of the following events is most likely to have occurred in this patient? Development of anti-RBC antibodies Reduced erythropoiesis from parvovirus infection Disseminated intravascular coagulation Superimposed dietary iron deficiency Accelerated extravascular hemolysis in the spleen

Hematopoietic stem cell defect is the correct answer. Aplastic anemia leads to marked pancytopenia. Many cases are idiopathic, although some can follow toxic exposures to chemotherapy drugs or to chemicals, such as benzene. Some cases may follow viral hepatitis infections. An intrinsic defect in stem cells, or T lymphocyte suppression of stem cells, can play a role in the development of aplastic anemia. Hemolysis is unlikely because the bilirubin is normal, and there is no history of an autoimmune disease. An increased susceptibility to complement lysis occurs in paroxysmal nocturnal hemoglobinuria as a result of mutations in the PIGA gene. It is unlikely that the patient has metastatic disease at this age, with no prior illness; metastases are more likely to produce a leukoerythroblastic peripheral blood appearance. Sequestration of peripheral blood cells in an enlarged spleen could account for mild pancytopenia, b

Question 18 1 / 1 pts A 28-year-old, previously healthy man has noted increasing fatigue for the past 6 months and formation of bruises after minimal trauma. Over the past 2 days, he has developed a cough. On physical examination, his temperature is 38.9° C, and he has diffuse rales in both lungs. He has no hepatosplenomegaly and no lymphadenopathy. Laboratory findings include a sputum culture positive for Streptococcus pneumoniae, hemoglobin of 7.2 g/dL, hematocrit of 21.7%, platelet count of 23,400/mm3, WBC count of 1310/mm3, prothrombin time of 13 seconds, partial thromboplastin time of 28 seconds, and total bilirubin of 1 mg/dL. The ANA test result is negative. What is the most likely explanation of these findings? Secondary hypersplenism Hematopoietic stem cell defect Increased susceptibility to lysis by complement Hemolysis of antibody-coated cells Metastatic adenocarcinoma to bone marrow

Telomerase is the correct answer. Telomerase is normally present in continuously dividing cells, such as hematopoietic stem cells, to prevent shortening of chromosomal telomeres; otherwise, shortened chromosomes cannot divide properly. Both genetic and acquired forms of aplastic anemia have been found that exhibit this mechanism. Alkaline phosphatase participates in bone remodeling. A deficiency of ADAMTS13, a metalloproteinase, can lead to accumulation of large von Willebrand multimers that promote platelet microaggregate formation, resulting in thrombotic thrombocytopenic purpura (TTP). Pyruvate kinase deficiency is one rare form of congenital anemia. Tyrosine kinases participate in cell growth regulation, and are better known to be involved with myeloproliferative disorders.

Question 19 1 / 1 pts In a study of idiopathic aplastic anemia, patients are found who have premature senescence of hematopoietic stem cells. Their hematopoietic cells have normal morphology, but there are fewer cells in myeloid, erythroid, and megakaryocytic cell lines. Which of the following enzymes is most likely deficient in their marrow stem cells? Telomerase Metalloproteinase Tyrosine kinase Pyruvate kinase Alkaline phosphatase

Exposure to medications is the correct answer. Her pancytopenia and absence of a reticulocytosis strongly suggest bone marrow failure. Aplastic anemia has no apparent cause in half of all cases. In other cases, drugs and toxins may be identified; drugs such as chemotherapeutic agents are best known for this effect. A preceding viral infection may be identified in some cases, but bacterial infections rarely cause aplastic anemias. Individuals with pancytopenia are subject to bleeding disorders because of the low platelet count and to infections because of the low WBC count. Dietary history would not be helpful because this patient's clinical and laboratory picture is not characteristic of iron deficiency or folate or vitamin B12 deficiency. The only known familial cause of aplastic anemia (Fanconi anemia) is rare. Menstrual history would be relevant if the patient had hypochromic microcytic anemia.

Question 20 1 / 1 pts A 44-year-old woman has a 2-week history of multiple ecchymoses on her extremities after only minor trauma. She also reports feeling extremely weak. Over the previous 24 hours, she has developed a severe cough productive of yellowish sputum. On physical examination, her temperature is 38.4° C, and she has diffuse crackles on all lung fields. Laboratory studies show hemoglobin, 7.2 g/dL; hematocrit, 21.4%; MCV, 88 μm3; platelet count, 35,000/mm3; and WBC count, 1400/mm3 with 20% segmented neutrophils, 1% bands, 66% lymphocytes, and 13% monocytes. The reticulocyte count is 0.1%. Which of the following historical findings would be most useful in determining the cause of her condition? Menstrual history Recent bacterial infection Exposure to medications Dietary habits Family history of anemias

Myelophthisic anemia is the correct answer. His prostatic adenocarcinoma has metastasized to the bone marrow. High alkaline phosphatase, hypercalcemia, and a leukoerythroblastic pattern in the peripheral blood (immature WBCs and RBCs) are a consequence of the tumor acting as a space-occupying lesion. Such myelophthisic anemias also may be caused by infections. The anemia of chronic disease is mild. Aplastic anemias are unlikely to include leukoerythroblastosis. Hemolytic anemia should be accompanied by an increase in bilirubin and no abnormalities in calcium metabolism. The MCV in this case is not in the megaloblastic range.

Question 21 1 / 1 pts A 77-year-old man has experienced increasing malaise and a 6-kg weight loss over the past year. He has noted more severe and constant back pain for the past 3 months. On physical examination, his temperature is 38.7° C. His prostate is firm and irregular when palpated on digital rectal examination. There is no organomegaly. A stool sample is negative for occult blood. Laboratory studies include a urine culture positive for Escherichia coli, serum glucose of 70 mg/dL, creatinine of 1.1 mg/dL, total bilirubin of 1 mg/dL, alkaline phosphatase of 293 U/L, calcium of 10.3 mg/dL, phosphorus of 2.6 mg/dL, and PSA of 25 ng/mL. CBC shows hemoglobin, 9.1 g/dL; hematocrit, 27.3%; MCV, 94 μm3; platelet count, 55,600/mm3; and WBC count, 3570/mm3 with 18% segmented neutrophils, 7% bands, 2% metamyelocytes, 1% myelocytes, 61% lymphocytes, 11% monocytes, and 3 nucleated RBCs per 100 WBCs. What is the most likely diagnosis? Aplastic anemia Hemolytic anemia Anemia of chronic disease Megaloblastic anemia Myelophthisic anemia

Erythroid hypoplasia is the correct answer. She has myasthenia gravis with thymoma and red cell aplasia. The edrophonium, an acetylcholinesterase inhibitor, will counteract the effect of the acetylcholine receptor antibodies of myasthenia gravis, but not improve muscle function with antibodies against voltage-gated calcium channels in Lambert-Eaton myasthenic syndrome (a paraneoplastic syndrome often associated with small cell lung carcinomas). The pulmonary findings suggest heart failure, and the tachycardia is consistent with high-output congestive heart failure from anemia. Pure red cell aplasia can be primary or arise secondarily to neoplasms, particularly thymic tumors, or autoimmune disorders. A lymphocytosis would be characteristic for lymphocytic leukemia, but this would not affect muscle strength, and lymphoblastic leukemia/lymphoma produces mediastinal masses in much younger persons. Megakaryocytic hyperpl

Question 22 1 / 1 pts A 48-year-old woman has experienced increasing weakness and dyspnea for the past 5 months. On physical examination, her temperature is 37° C, pulse 100/minute, respiratory rate 19/min, and blood pressure 115/75 mm Hg. Auscultation of the lungs reveals bilateral basilar crackles. Muscle strength diminishes from 5/5 to 4/5 with repetitive movement of her arms. Her strength returns with administration of an acetylcholinestrase inhibitor. A chest CT scan reveals a 6-cm circumscribed anterior mediastinal mass. Which of the following findings is most likely to be present on microscopic examination of her bone marrow biopsy? Megakaryocytic hyperplasia Plasmacytosis Lymphocytosis Myelofibrosis Erythroid hypoplasia Metastatic carcinoma

Serum ferritin is the correct answer. With RBC microcytosis, iron deficiency anemia must be considered. It could be a nutritional deficiency in children and pregnant women, but more likely is due to chronic blood loss in adults. The ferritin concentration is a measure of storage iron because it is derived from the total body storage pool in the liver, spleen, and marrow. About 80% of functional body iron is contained in hemoglobin; the remainder is in muscle myoglobin. Individuals with severe liver disease can have an elevated serum ferritin level because of its release from liver stores. A bone marrow biopsy specimen provides a good indication of iron stores because the iron stain of the marrow shows hemosiderin in macrophages, but such a biopsy is an expensive procedure. Some patients with hemoglobinopathies, such as β-thalassemias, also can have a microcytic anemia, but this is far less common than iron deficien

Question 23 1 / 1 pts A 54-year-old, previously healthy man has experienced minor fatigue on exertion for the past 9 months. On physical examination, there are no remarkable findings. Laboratory studies show hemoglobin of 11.7 g/dL, hematocrit of 34.8%, MCV of 73 μm3, platelet count of 315,000/mm3, and WBC count of 8035/mm3. Which of the following is the most sensitive and cost-effective test that the physician should order to help to determine the cause of these findings? Hemoglobin electrophoresis Serum iron Serum ferritin Bone marrow biopsy Serum haptoglobin Serum transferrin

Hepcidin is the correct answer. Iron absorption from the gut is tightly controlled. When body iron stores are adequate, absorption of dietary iron via DMT-1 in the duodenum is retarded, and release of iron from storage pools is inhibited. When body iron stores decrease, as with chronic blood loss, iron absorption increases. The liver-derived plasma peptide hepcidin has been found to be the iron absorption regulator. Hepcidin levels increase when iron stores are high. Such fine control of iron absorption may fail, as in patients with ineffective erythropoiesis (e.g., β-thalassemia) who continue to absorb iron despite excess storage iron. Hepcidin levels are inappropriately low with both hereditary and acquired hemochromatosis. DMT-1 is an iron transporter that moves nonheme iron from the gut lumen to duodenal epithelium. Hemosiderin is an aggregated form of ferritin that does not circulate and is found only in tissu

Question 24 1 / 1 pts A clinical study is performed using adult patients diagnosed with peptic ulcer disease, chronic blood loss, and hypochromic microcytic anemia. Their serum ferritin levels average 5 to 7 ng/mL. The rate of duodenal iron absorption in this study group is found to be much higher than in a normal control group. After treatment with omeprazole and clarithromycin, study group patients have hematocrits of 40% to 42%, MCV of 82 to 85 μm3, and serum ferritin of 30 to 35 ng/mL. Measured rates of iron absorption in the study group after therapy are now decreased to the range of the normal controls. Which of the following substances derived from liver is most likely to have been decreased in the study group patients before therapy, and returned to normal after therapy? Transferrin HLA-like transmembrane protein Divalent metal transporter-1 (DMT-1) Hemosiderin Hepcidin

Anemia of chronic disease is the correct answer. The increased ferritin concentration and reduced total iron-binding capacity are typical of anemia of chronic disease, such as an autoimmune disease. Increased levels of cytokines such as interleukin-6 lead to increased hepatic production of hepcidin that stops ferroportin from releasing storage iron, promoting sequestration of storage iron, with poor use for erythropoiesis. Secretion of erythropoietin by the kidney is impaired. Various underlying diseases, including cancer, collagen vascular diseases, and chronic infections, can produce this pattern of anemia. Iron deficiency would produce a microcytic anemia, with a low serum ferritin level and reduced hepcidin production. Aplastic anemia is unlikely because the platelet count and WBC count are normal. Megaloblastic anemias are macrocytic without an increase in iron stores. Microangiopathic hemolytic anemias are cau

Question 25 1 / 1 pts A 39-year-old man has experienced chronic fatigue and weight loss for the past 3 months. There are no remarkable findings on physical examination. Laboratory studies show hemoglobin, 10.0 g/dL; hematocrit, 30.3%; MCV, 91 μm3; platelet count, 240,000/mm3; WBC count, 7550/mm3; serum iron 80 μg/dL; total iron-binding capacity, 145 μg/dL; and serum ferritin, 565 ng/mL. Serum erythropoetin levels are low for the level of Hb and hepcidin levels are elevated. Which of the following is the most likely diagnosis? Aplastic anemia Anemia of chronic disease Thalassemia minor Microangiopathic hemolytic anemia Iron deficiency anemia Megaloblastic anemia

Inadequate usage of stored iron is the correct answer. The iron concentration and iron-binding capacity are low; however, in contrast to the finding in anemia of iron deficiency, the serum ferritin level is increased. This increase is typical of anemia of chronic disease. In this case, the chronic disease is rheumatoid arthritis. Underlying chronic inflammatory or neoplastic diseases increase the secretion of cytokines such as interleukin-1, tumor necrosis factor, and interferon-γ. These cytokines promote sequestration of iron in storage compartments and depress erythropoietin production. Autoantibody hemolytic anemias occur in several autoimmune diseases, such as systemic lupus erythematosus, but not usually in patients with rheumatoid arthritis, as in this case. Normal serum haptoglobin rules out intravascular hemolysis; iron is recycled at a rapid rate. Impaired synthesis of β-globin chains gives rise to β-tha

Question 26 1 / 1 pts A 45-year-old woman has experienced worsening arthritis of her hands and feet for the past 15 years. On physical examination, there are marked deformities of the hands and feet, with ulnar deviation of the hands and swan-neck deformities of the fingers. Laboratory studies show an elevated level of rheumatoid factor. CBC shows hemoglobin, 11.6 g/dL; hematocrit, 34.8%; MCV, 87 μm3; platelet count, 268,000/mm3; and WBC count, 6800/mm3. There is a normal serum haptoglobin level, serum iron concentration of 20 μg/dL, total iron-binding capacity of 195 μg/dL, percent saturation of 10.2, and serum ferritin concentration of 317 ng/mL. No fibrin split products are detected. The reticulocyte concentration is 1.1%. What is the most likely mechanism underlying this patient's hematologic abnormalities? Impaired synthesis of β-globin chains Autoantibodies against RBC membranes Mutation in the phosphatidylinositol glycan A (PIGA) gene Inadequate usage of stored iron Space-occupying lesions in the bone marrow Sequestration of RBCs in splenic sinusoids

Occult malignancy is the correct answer. The figure shows RBC hypochromia and microcytosis, consistent with iron deficiency, the most common cause for anemia worldwide, either from nutritional deficiency or chronic blood loss. The lack of iron impairs heme synthesis. The marrow response is to "downsize" the RBCs, resulting in a microcytic and hypochromic anemia. At this patient's age, bleeding from an occult malignancy, such as a colonic adenocarcinoma, should be strongly suspected as the cause of iron deficiency. An autoimmune hemolytic anemia would appear as a normocytic anemia or as a slightly increased MCV with pronounced reticulocytosis. Macrocytosis would accompany a history of chronic alcoholism, probably because of poor diet and folate deficiency. Thalassemias may result in a microcytosis, but β-thalassemia major causes severe anemia soon after birth, and survival to age 73 years is unlikely. By this

Question 27 1 / 1 pts A 73-year-old man takes no medications and has had no prior major illnesses or surgeries. For the past year, he has become increasingly tired and listless. Physical examination shows that he appears pale but has no hepatosplenomegaly and no deformities. CBC shows hemoglobin, 9.7 g/dL; hematocrit, 29.9%; MCV, 69.7 mm3; RBC count, 4.28 million/mm3; platelet count, 331,000/mm3; and WBC count, 5500/mm3. His peripheral blood smear is shown in the attached figure. Which of the following is the most likely underlying condition causing this patient's findings? Anemia_q_4.jpg Hemophilia A Chronic alcohol abuse Vitamin B12 deficiency β-Thalassemia major Occult malignancy Autoimmune hemolytic anemia

Chronic blood loss is the correct answer. The marked reticulocytosis and marrow hyperplasia indicate that the marrow is responding to a decrease in RBCs. The reticulocytes are larger RBCs that slightly increase the MCV. An aplastic marrow is very hypocellular and unable to respond to anemia; it is associated with pancytopenia. The normal Coombs test results exclude an autoimmune hemolytic anemia. Iron deficiency impairs the ability of the marrow to mount a significant and sustained reticulocytosis. Iron deficiency anemia is typically microcytic and hypochromic, but could be partially masked here by reticulocytosis, which would not be as marked if iron were not available, but his diet is supplying needed iron. Infiltrative disorders, such as metastases in the marrow, would impair the ability to mount a reticulocytosis of this degree.

Question 28 1 / 1 pts A 65-year-old man has experienced worsening fatigue for the past 5 months. On physical examination, he is afebrile and has a pulse of 91/min, respirations of 18/min, and blood pressure of 105/60 mm Hg. There is no organomegaly. A stool sample is positive for occult blood. Laboratory findings include hemoglobin of 5.9 g/dL, hematocrit of 18.3%, MCV of 99 μm3, platelet count of 250,000/mm3, and WBC count of 7800/mm3. The reticulocyte concentration is 3.9%. No fibrin split products are detected, and direct and indirect Coombs test results are negative. A bone marrow biopsy specimen shows marked erythroid hyperplasia. Which of the following conditions best explains these findings? Metastatic carcinoma Iron deficiency anemia Autoimmune hemolytic anemia Chronic blood loss Aplastic anemia

Participates in the transfer of a methyl group from N5-methyltetrahydrofolate to homocysteine (A) would be correct if the transfer was to homocysteine. (B) is incorrect because vitamin B12 is not a cofactor for dihydrofolate reductase. (D) is incorrect because vitamin B12 is being given to this patient parenterally, not enterally. (E) is incorrect because vitamin B12 is extrinsic factor. (F) is incorrect because vitamin B12 is not a cofactor for folate reductase.

Question 32 1 / 1 pts A 45-year-old man who was recently diagnosed with pernicious anemia is started on lifelong administration of cyanocobalamin. Which of the following describes a molecular mechanism of action of this drug that will help to alleviate the symptoms of this patient's condition? Participates in the transfer of a methyl group from N5-methyltetrahydrofolate to homocysteine Participates in the conversion of folic acid to dihydrofolate Stimulates the production and secretion of extrinsic factor Stimulates the production and secretion of intrinsic factor Participates in the conversion of dihydrofolate to tetrahydrofolate Participates in the transfer of a methyl group from N5-methyltetrahydrofolate to L-methylmalonyl-CoA

Epoetin alfa Normochromic normocytic anemia can occur in patients with chronic kidney disease. This is due to reduced production of erythropoietin, which is made in the kidney. (B) - parenteral iron for the treatment of iron deficiency anemia. (C) - cyanocobalamin is used to treat megaloblastic anemia due to B12 deficiency. (D) - folic acid is used to treat megaloblastic anemia due to folate deficiency. (E) - deferoxamine is a chelating agent used to treat iron overload.

Question 33 1 / 1 pts A 60-year-old woman is diagnosed with normochromic normocytic anemia. The patient was recently placed on hemodialysis due to increasingly worsening chronic kidney disease. Which of the following drugs would be most appropriate to help alleviate her anemia? Epoetin alfa Ferric gluconate Folic acid Deferoxamine Cyanocobalamin

Ferrous gluconate Her symptoms and laboratory results indicate that the patient has iron-deficiency anemia. Ferrous gluconate, which is an oral iron preparation is appropriate for this patient. (A) and (F) are incorrect because these are parenteral iron preparations.

Question 34 1 / 1 pts A 14-year-old girl presents to her family practitioner with complaints of severe fatigue and shortness of breath upon exertion. The patient reports that these symptoms have gotten progressively worse over the past several months, especially after she began participating on her high school's track and field team. Physical examination reveals several flat and concave-shaped fingernails, a swollen and smooth-appearing tongue, and pallor of the mucous membranes. Laboratory investigations reveal the following: RBCs: 2.8 million/mm3 (normal: 3.5-5.5) MCHC: 26% (normal: 31-36) MCV: 70 fL (normal: 80-100) Serum transferrin: 410 mcg/100 mL (normal: 300-360) Transferrin saturation: 7% (normal: 20-50) Plasma ferritin: 8 mcg/L (normal: 40-160) Serum Vitamin B12: 220 pg/mL (normal: 200-800) Serum Folate: 7.4 ng/mL (normal: 5.4-40.0) The physician prescribes an orally administered drug to treat the patient's condition. Which of the following drugs was most likely prescribed for this patient? Folic acid Epoetin alfa Iron dextran Ferric gluconate Cyanocobalamin Ferrous gluconate

Intramuscular cyanocobalamin His symptoms and laboratory results indicate that the patient is suffering with megaloblastic anemia caused by a vitamin B12 deficiency, probably as the result of a lack of production of intrinsic factor (pernicious anemia). This necessitates parenteral administration of vitamin B12 (why (B) is incorrect).

Question 35 1 / 1 pts A 62-year-old man complains of paresthesia in his fingers and toes, generalized weakness, clumsiness, and an increasingly unsteady gait. Laboratory investigations reveal the following results: MCV: 120 fL (normal: 80-100) MCH: 41.3 pg/cell (normal: 25.4-34.6) MCHC: 36% Hb/cell (normal: 31-36%) Serum folate: 8 nmol/L (normal: >5) Serum vitamin B12: 120 pg/mL (normal: 200-900) Based on these results, the physician prescribes life-long administration of an appropriate drug. Which of the following drugs was most likely prescribed to this patient? Intramuscular folic acid Oral leucovorin Oral cyanocobalamin Intramuscular cyanocobalamin Intramuscular leucovorin Oral folic acid

Deferoxamine The patient is suffering from acute iron toxicity. The patient's mother was likely prescribed iron supplementation after the birth of her child. Deferoxamine is indicated for the therapy of this condition and it is administered parenterally. (F) Deferasairox is administered orally, it is used to treat chronic not acute iron toxicity.

Question 36 1 / 1 pts A 6-year-old girl is brought to the emergency department because she started vomiting blood, passing bloody diarrhea, and complaining of severe abdominal pain. Upon investigation, it is discovered that the child consumed numerous tablets of one of her mother's medications, which was prescribed after the mother's recent delivery of her second child. The attending physician orders immediate intravenous administration of an appropriate antidote. Which of the following drugs was most likely administered to this patient to treat her presenting condition? Epoetin alfa Leucovorin Deferoxamine Darbepoetin alfa Ferrous gluconate Deferasirox

Correct answer is Glucose-6-phosphate dehydrogenase deficiency, which is an X-linked disorder that affects about 10% of African-American males. The lack of this enzyme subjects hemoglobin to damage by oxidants, including drugs such as primaquine, sulfonamides, nitrofurantoin, phenacetin, and aspirin (in large doses). Infection can also cause oxidative damage to hemoglobin. Heinz bodies are denatured hemoglobin, and they damage the RBC membrane, giving rise to intravascular hemolysis. The "bite cells" result from the attempts of overeager splenic macrophages to pluck out the Heinz bodies, adding an element of extravascular hemolysis. Heterozygotes with α-thalassemia (1 or 2 abnormal genes out of 4 total α-globin genes) have no major problems, but in cases of α-thalassemia major, perinatal death is the rule. Likewise, β-thalassemia minor and sickle cell trait are conditions usually with no major problems and n

Question 4 1 / 1 pts A 23-year-old African-American man passes dark reddish brown urine 3 days after taking an anti-inflammatory medication that includes phenacetin. He is surprised, because he has been healthy all his life and has had no major illnesses. On physical examination, he is afebrile, and there are no remarkable findings. CBC shows a mild normocytic anemia, but the peripheral blood smear shows precipitates of denatured globin (Heinz bodies) with supravital staining and scattered "bite cells" in the population of RBCs. Which of the following is the most likely diagnosis? Glucose-6-phosphate dehydrogenase deficiency β-Thalassemia minor α-Thalassemia minor Sickle cell trait Warm antibody autoimmune hemolytic anemia Abnormal ankyrin in RBC cytoskeletal membrane

Correct answer is Phosphatidylinositol glycan A (PIGA). Paroxysmal nocturnal hemoglobinuria (PNH) is a disorder that results from an acquired stem cell membrane defect produced by a PIGA gene mutation that prevents the membrane expression of certain proteins that require a glycolipid anchor. These include proteins that protect cells from lysis by spontaneously activated complement. As a result, RBCs, granulocytes, and platelets are exquisitely sensitive to the lytic activity of complement. The RBC lysis is intravascular, so patients can have hemoglobinuria (dark urine). Defects in platelet function are believed to be responsible for venous thrombosis. Recurrent infections can be caused by impaired leukocyte functions. Patients with PNH may develop acute leukemia or aplastic anemia as complications. Mutations in the β-globin chain can give rise to hemoglobinopathies such as sickle cell anemia. Patients with factor V

Question 5 1 / 1 pts A 16-year-old boy notes passage of dark urine. He has a history of multiple bacterial infections and venous thromboses for the past 10 years, including portal vein thrombosis in the previous year. On physical examination, his right leg is swollen and tender. CBC shows hemoglobin, 9.8 g/dL; hematocrit, 29.9%; MCV, 92 μm3; platelet count, 150,000/mm3; and WBC count, 3800/mm3 with 24% segmented neutrophils, 1% bands, 64% lymphocytes, 10% monocytes, and 1% eosinophils. He has a reticulocytosis, and his serum haptoglobin level is very low. A mutation affecting which of the following gene products is most likely to give rise to this clinical condition? Factor V Spectrin Glucose-6-phosphate dehydrogenase Prothrombin G20210A Phosphatidylinositol glycan A (PIGA) β-Globin chain

Correct answer is oxidative injury to hemoglobin. Glucose-6-phosphate dehydrogenase (G6PD) deficiency predisposes the hemoglobin in RBCs to oxidative injury from drugs such as primaquine, and can induce hemolysis. Oxidant injury to hemoglobin produces inclusion of denatured hemoglobin within RBCs. The inclusions damage the cell membrane directly, giving rise to intravascular hemolysis. These damaged RBCs have reduced membrane deformability, and they are removed from the circulation by the spleen. The remaining mechanisms listed are not directly drug dependent. Hemolytic anemias with antibody coating RBCs can occur with autoimmune diseases, prior transfusion, and erythroblastosis fetalis. Impaired RBC nuclear maturation occurs as a result of vitamin B12 or folate deficiency. Impaired globin synthesis occurs in thalassemias. Complement lysis is enhanced in paroxysmal nocturnal hemoglobinuria, which results from mutati

Question 6 1 / 1 pts A 30-year-old, previously healthy man from Lagos, Nigeria, passes dark brown urine 2 days after starting the prophylactic antimalarial drug primaquine. On physical examination, he appears pale and is afebrile. There is no organomegaly. Laboratory studies show that his serum haptoglobin level is decreased. Which of the following is the most likely explanation of these findings? Impaired globin chain synthesis Impaired DNA synthesis Oxidative injury to hemoglobin Mechanical fragmentation of RBCs as a result of vascular narrowing Increased susceptibility to complement-induced lysis Antibody-mediated hemolysis Reduced deformability of RBC membrane

Correct answer is systemic lupus erythematosus. This patient has a warm autoimmune hemolytic anemia secondary to systemic lupus erythematosus (SLE). A positive Coombs test result indicates the presence of anti-RBC antibodies in the serum and on the RBC surface. Most cases of warm autoimmune hemolytic anemia are idiopathic, but one fourth occur in individuals with an identifiable autoimmune disease, such as SLE; in other cases, drugs are the cause. The immunoglobulin coating the RBCs acts as an opsonin to promote splenic phagocytosis. Nucleated RBCs can be seen in active hemolysis because the marrow compensates by releasing immature RBCs. Septicemia is more likely to lead to a microangiopathic hemolytic anemia. The increased RBC destruction in hereditary spherocytosis is extravascular and not immune mediated. Infections such as mononucleosis and Mycoplasma are associated with cold autoimmune hemolytic anemia (with an

Question 7 1 / 1 pts A 34-year-old woman reports becoming increasingly tired for the past 5 months. On physical examination, she is afebrile and has mild splenomegaly. Laboratory studies show a hemoglobin concentration of 10.7 g/dL and hematocrit of 32.3%. The peripheral blood smear shows spherocytes and rare nucleated RBCs. Direct and indirect Coombs test results are positive at 37° C, although not at 4° C. Which of the following underlying diseases is most likely to be diagnosed in this patient? Escherichia coli septicemia Infectious mononucleosis Mycoplasma pneumoniae infection Hereditary spherocytosis Systemic lupus erythematosus

Complement C3b is the correct answer. Cold agglutinin disease has antibody (usually IgM) coating RBCs. The IgM antibodies bind to the RBCs at low temperature at peripheral body sites and fix complement; however, complement is not lytic at this temperature. With an increase in temperature within core internal organs, the IgM is dissociated from the cell, leaving behind C3b. Most of the hemolysis occurs extravascularly in the cells of the mononuclear phagocyte system, such as Kupffer cells in the liver, or splenic macrophages, because the coating of complement C3b acts as an opsonin. IgG is typically involved in warm antibody hemolytic anemia, which is chronic and is not triggered by cold. Raynaud phenomenon occurs in exposed, colder areas of the body, such as the fingers and toes. The patient probably has an elevated cold agglutinin titer. Histamine is released in type I hypersensitivity reactions. Fibronectin is an

Question 8 1 / 1 pts A 22-year-old woman has experienced malaise and a sore throat for 2 weeks. Her fingers turn white on exposure to cold. On physical examination, she has a temperature of 37.8° C, and the pharynx is erythematous. Laboratory findings include a positive monospot (heterophile antibody) test result. Direct and indirect Coombs test results are positive at 4° C, although not at 37° C. Which of the following molecules bound on the surfaces of the RBCs most likely accounts for these findings? Complement C3b Fibronectin α2-Macroglobulin Histamine IgE

Correct answer is spectrin cytoskeletal protein. Hereditary spherocytosis is a condition in which a mutation affects one of several membrane cytoskeletal proteins. Spectrin and related proteins are cytoskeletal proteins that are important in maintaining the RBC shape. These proteins include ankyrin (most common) and band 4.2, which binds spectrin to the transmembrane ion transporter; band 3; and protein 4.1, which binds the "tail" of spectrin to another transmembrane protein, glycophorin A. The abnormal RBCs with such mutant proteins are less deformable, lack central pallor on a peripheral blood smear, and they are sequestered and destroyed in the spleen. Thalassemias with abnormal α-globin or β-globin chains are associated with hypochromic microcytic anemias. Iron deficiency affects the heme portion of hemoglobin, leading to hypochromia and to microcytosis. Carbonic anhydrase in RBCs helps to maintain bufferi

A 28-year-old woman has had a constant feeling of lethargy since childhood. On physical examination, she is afebrile and has a pulse of 80/min, respirations of 15/min, and blood pressure of 110/70 mm Hg. The spleen tip is palpable, but there is no abdominal pain or tenderness. Laboratory studies show hemoglobin of 11.7 g/dL, platelet count of 159,000/mm3, and WBC count of 5390/mm3. The peripheral blood smear shows small round erythrocytes that lack a zone of central pallor. An inherited abnormality in which of the following RBC components best accounts for these findings? Spectrin cytoskeletal protein Heme with porphyrin ring α-Globin chain β-Globin chain Glucose-6-phosphate dehydrogenase Carbonic anhydrase

Correct answer is positive Coombs test. She has a circulating antibody against her RBCs leading to hemolytic anemia. The indirect antiglobulin (Coombs) test detects antibody in the plasma. The direct antiglobulin (Coombs) test detects antibody bound to RBCs. Autoimmune hemolytic anemias can be a feature of autoimmune diseases, such as systemic lupus erythematosus in this woman. Most of the hemolysis is extravascular in the spleen, but some can be intravascular. The reticulocyte count is typically increased (polychromasia) with hemolysis, and serum haptoglobin is diminished. An elevated D-dimer suggests a microangiopathic hemolytic anemia, but she has no schistocytes on the peripheral blood smear. Increased osmotic fragility is a feature of RBCs in paroxysmal nocturnal hemoglobinuria. Her mild macrocytosis indicates increased reticulocytosis, not vitamin B12 deficiency, and hemolysis is not part of pernicious anemia.

Question 10 1 / 1 pts A 29-year-old woman has had fatigue with dizziness for the past 5 months. On physical examination, she has an erythematous malar rash. She has no lymphadenopathy, but there is a palpable spleen tip. She is afebrile. Laboratory studies show hemoglobin, 8.9 g/dL; hematocrit, 27.8%; MCV, 103 μm3; RBC distribution width index, 22; WBC count, 8650/mm3; platelet count, 222,000/mm3; and reticulocyte count, 3.3%. The peripheral blood smear shows polychromasia, but no schistocytes. Her serum total bilirubin is 3.2 mg/dL with direct bilirubin 0.8 mg/dL, and haptoglobin is 5 mg/dL. Antinuclear antibody and anti-double-stranded DNA tests are positive. What additional laboratory test finding is she most likely to have? Serum ferritin 240 ng/mL Serum cobalamin (vitamin B12) 50 pg/mL D-dimer 10 μg/mL Positive Coombs test Increased RBC osmotic fragility

Correct answer is intravascular disruption. Mechanical trauma to RBCs is possible, but typically is not severe. It can follow strenuous exercises involving repeated blows to body parts. Complement-mediated lysis is a feature of immunohemolytic anemias. Increased osmotic fragility is noted in spherocytes. Sickle cell anemia is not likely to be found in the population groups in the countries noted, and persons with this disease are not likely to be playing rugby. Splenic sequestration is a feature of hemolytic anemias due to membrane defects and antibodies.

Question 11 1 / 1 pts A 29-year-old rugby player takes part in a particularly contentious game between New Zealand and South Africa. He is the forward prop in the scrums, hitting hard and being hit hard by other players. He feels better after downing several pints of beer following the game, but notes darker urine. Urinalysis is positive for blood. Which of the following pathogenic mechanisms underlies change in the color of urine? Complement lysis Osmotic fragility Intravascular disruption Splenic sequestration Sinusoidal sickling

Correct answer is Plasmodium falciparum. Throughout human history, malaria has influenced the increasing gene frequency of hemoglobin S. Individuals who are heterozygous for hemoglobin S have the sickle cell trait. They are more resistant to malaria, particularly the most malignant form caused by P. falciparum, because the parasites grow poorly or die at low oxygen concentrations, perhaps because of low potassium levels caused by potassium efflux from RBCs on hemoglobin sickling. The malarial parasite has difficulty completing its life cycle, even in cells with moderate amounts of hemoglobin S, as found in heterozygotes, giving a selective advantage to such persons living in endemic areas for falciparum malaria. Borrelia burgdorferi is the spirochete that causes Lyme disease. Clostridium perfringens may produce gas gangrene after soft-tissue injuries. Cryptococcus neoformans can cause granulomatous disease in immuno

Question 12 1 / 1 pts In an epidemiologic study of anemias, the findings show that there is an increased prevalence of anemia in individuals of West African ancestry. By hemoglobin electrophoresis, some individuals within this region have increased hemoglobin S levels. The same regions also have a high prevalence of an infectious disease. Which of the following infectious agents is most likely to be endemic in the region where such anemia shows increased prevalence? Clostridium perfringens Cryptococcus neoformans Treponema pallidum Borrelia burgdorferi Plasmodium falciparum Trypanosoma brucei

Correct answer is Hemolysis of antibody-coated cells. The infant most likely has erythroblastosis fetalis because maternal antibodies are coating fetal RBCs. A fetal-maternal hemorrhage in utero or at the time of delivery in a previous pregnancy (or with previous transfusion of incompatible blood) can sensitize the mother, resulting in production of irregular IgG antibodies. In subsequent pregnancies, these antibodies (in contrast to the naturally occurring IgM antibodies) can cross the placenta to attach to fetal cells, leading to hemolysis. In the past, most cases were caused by Rh incompatibility (e.g., Rh-negative mother, Rh-positive infant), but the use of RhoGAM administered at birth to Rh-negative mothers has eliminated almost all such cases when recognized. Other, less common blood group antigens can be involved in this process, however. The other conditions listed are not antibody mediated. A stem cell defe

Question 13 1 / 1 pts An infant is born at 34 weeks' gestation to a 28-year-old woman, G3, P2. At birth, the infant is observed to be markedly hydropic and icteric. A cord blood sample is taken, and direct Coombs test result is positive for the infant's RBCs. Which of the following is the most likely mechanism for the findings in this infant? Oxidative injury to hemoglobin Impaired globin synthesis Hemolysis of antibody-coated cells Reduced deformability of RBC membranes Mechanical fragmentation of RBCs Hematopoietic stem cell defect

Correct answer is Plasmodium vivax. This is benign tertian malaria. The bite of the Anopheles mosquito introduces sporozoites, which travel to the liver to reproduce. The resulting merozoites are released into the bloodstream and infect RBCs. Asexual reproduction within the RBCs yields trophozoites, and periodic hemolysis with release of the parasites produces the characteristic clinical findings. Aspergillus organisms invade blood vessels and cause thrombosis, but hemolysis of RBCs is inconsequential. Babesiosis is far less common than malaria, is endemic to the northeastern United States, and does not produce episodic fevers. Dirofilaria is the heartworm found in dogs, which rarely infects humans and does not cause hemolysis. Similar to other gram-negative bacteria, Escherichia coli can release lipopolysaccharide, which causes severe sepsis and possible disseminated intravascular coagulation, a microangiopathic he

Question 14 1 / 1 pts A 22-year-old woman after returning from a trip to Africa has experienced febrile episodes over the past 2 weeks. On physical examination, her temperature is 37.5° C, pulse is 82/min, respirations are 18/min, and blood pressure is 105/65 mm Hg. Laboratory studies show hemoglobin of 10.8 g/dL, hematocrit of 32.5%, platelet count of 245,700/mm3, and WBC count of 8320/mm3. The serum haptoglobin level is decreased, and direct and indirect Coombs test results are negative. The reticulocyte count is increased. The prothrombin time is 12 seconds, and the partial thromboplastin time is 31 seconds. She is observed over the next week and found to have temperature spikes to 39.1° C, with shaking chills every 48 hours. Infection with which of the following organisms is most likely to cause this patient's illness? Escherichia coli Babesia microti Plasmodium vivax Dirofilaria immitis Wuchereria bancrofti Aspergillus niger

Correct answer is immune-mediated hemolysis. Drug-induced hemolytic anemias are neither common nor severe enough to be recognized, since the hemolysis is mainly extravascular. However, many patients receive drugs, so the potential for a drug reaction exists, and this immune-mediated mechanism must be distinguished from other causes for anemia. Cephalosporins are the most frequent drugs implicated. Treatment consists of cessation of therapy with the drug, because most cases are due to drug-dependent antibody formation. Nutrient deficiencies reduce marrow production, so a reticulocytosis is unlikely. DIC is unlikely with a normal platelet count. Parvovirus infection may suppress erythropoiesis transiently in individuals with normal red cells, but may precipitate an aplastic crisis in those with a hemoglobinopathy. Persons with abnormal red cells are likely to have a history of anemia. Hemoglobinopathies are not Coombs

Question 15 1 / 1 pts A 33-year-old previously healthy man with persistent fever and heart murmur is diagnosed with infective endocarditis. He receives a high dosage of a cephalosporin antibiotic during the next 10 days. He now has increasing fatigue. On physical examination he has tachycardia and scleral icterus. Laboratory studies show a hemoglobin level of 7.5 g/dL, platelet count of 261,000/mm3, and total WBC count of 8300/mm3. The direct Coombs test is positive. The periperal blood smear shows reticulocytosis. Which of the following is the most likely cause for his anemia? Disseminated intravascular coagulopathy Inherited hemoglobinopathy Dietary nutrient deficiency Infection with parvovirus Immune-mediated hemolysis RBC cytoskeletal protein disorder

Correct answer is Plasmodium falciparum. This child has cerebral malaria, and the smear shows numerous ring forms of the parasites in RBCs. Infection occurs via the bite of an Anopheles mosquito. Malarial parasites infect RBCs, causing hemolysis and anemia. Falciparum malaria is the worst form. The parasites tend to be released from cells at periodic intervals, leading to periodic fever and chills. The parasites adhere to the vascular endothelium and lead to ischemia in various organs, including the brain with consequent acute cerebral edema. There is hemolytic anemia. The liver and spleen become progressively enlarged. Babesiosis is a rare, tick-borne disease found in the northeastern United States, which can produce a hemolytic anemia, but the organisms produce a classic "tetrad" in RBCs. Lyme disease, caused by Borrelia burgdorferi, is best known for producing chronic arthritis, but meningoencephalitis, neuri

Question 16 1 / 1 pts A 7-year-old child has had worsening headaches and is obtunded for the past 2 days. Physical examination shows temperature of 39.5° C, pulse of 103/min, respirations of 18/min, and blood pressure of 90/55 mm Hg. There is bilateral papilledema on funduscopic examination. No focal neurologic deficits are noted. Palpation of the abdomen reveals hepatosplenomegaly. Laboratory findings show hemoglobin, 9.5 g/dL; hematocrit, 28.8%; MCV, 101 μm3; platelet count, 145,000/mm3; WBC count, 6920/mm3; Na+, 146 mmol/L; K+, 5.5 mmol/L; Cl-, 106 mmol/L; CO2, 26 mmol/L; creatinine, 2.3 mg/dL; urea nitrogen, 22 mg/dL; LDH, 1095 U/L; and amylase, 45 U/L. The peripheral blood smear is shown in the figure. What infectious agent is most likely to produce these findings? Plasmodium falciparum Borrelia burgdorferi Leishmania donovani Trypanosoma brucei Babesia microti Wuchereria bancrofti

Extensive fibrosis is the correct answer. Teardrop RBCs are indicative of a myelophthisic disorder (i.e., something filling the bone marrow, such as fibrous connective tissue). The leukoerythroblastosis, including immature RBCs and WBCs, is most indicative of myelofibrosis. Splenomegaly also is typically seen in myelofibrosis. A leukoerythroblastic picture also can be seen in patients with infections and metastases involving the marrow. Hyperplasia of erythroid normoblasts occurs in hemolytic anemias. Leukoerythroblastosis is not seen in hemolytic anemias. Replacement of marrow by fat occurs in aplastic anemia, which is characterized by pancytopenia. The presence of megaloblasts in the marrow indicates folate or vitamin B12 deficiency—both cause macrocytic anemia. Marrow packed with myeloblasts is typical of acute myeloid leukemia. In this condition, the peripheral blood also would show many myeloblasts and failur

Question 17 1 / 1 pts An 83-year-old man complains of worsening malaise and fatigue over the past 5 months. On physical examination, he is afebrile and normotensive. The spleen tip is palpable. A CBC shows hemoglobin, 10.6 g/dL; hematocrit, 29.8%; MCV, 92 μm3; platelet count, 95,000/mm3; and WBC count, 4900/mm3 with 63% segmented neutrophils, 7% bands, 2% metamyelocytes, 1% myelocytes, 22% lymphocytes, 5% monocytes, and 3 nucleated RBCs per 100 WBCs. The peripheral blood smear shows occasional teardrop cells. An examination of the bone marrow biopsy specimen and smear is most likely to show which of the following findings? Extensive fibrosis Fatty replacement Many megaloblasts Numerous myeloblasts Erythroid hyperplasia

Diminished nuclear maturation from impaired DNA synthesis is the correct answer. Chronic alcohol abuse can lead to folate deficiency, giving rise to megaloblastic anemia. Folic acid and vitamin B12 act as coenzymes in DNA synthetic pathways. A deficiency of either impairs the normal process of nuclear maturation. The hematopoietic cell nuclei remain large and primitive looking, giving rise to megaloblasts. The mature RBCs are larger than normal (macrocytes). Neutrophils often show defective segmentation, manifested by extra nuclear lobes. The nuclear maturation defect affects all rapidly dividing cells in the body. Patients with chronic alcohol abuse can have thrombocytopenia and leukopenia, often because of secondary hypersplenism (alcoholic cirrhosis, leading to splenomegaly). Polychromatophilic RBCs represent reticulocytes, and their number is reduced because of the failure of marrow to produce adequate numbers o

Question 29 1 / 1 pts A 62-year-old man is taken to the emergency department in a state of inebriation. He is well known there because this scenario has been repeated many times over 15 years. On physical examination, he is afebrile. The spleen tip is palpable, and the liver edge is firm. Laboratory studies show hemoglobin of 8.2 g/dL, hematocrit of 25.1%, MCV of 107 μm3, platelet count of 135,000/mm3, and WBC count of 3920/mm3. The peripheral blood smear shows prominent anisocytosis and macrocytosis. Polychromatophilic RBCs are difficult to find. A few of the neutrophils show six to seven nuclear lobes. Which of the following is the most likely explanation of these findings in his peripheral blood cells? Diminished nuclear maturation from impaired DNA synthesis Imbalance in synthesis of α-globin and β-globin chains Increased susceptibility to lysis by complement Reduced deformability of RBC membranes Extravascular hemolysis of antibody-coated cells

Correct answer is decrease in splenic RBC sequestration and lysis. In patients with hereditary spherocytosis, spheroidal cells are trapped and destroyed in the spleen because the abnormal RBCs have reduced deformability. Splenectomy is beneficial because the spherocytes are no longer detained by the spleen. Splenectomy has no effect on the synthesis of spectrin or RBC deformability; the RBCs in spherocytosis are not killed by opsonization. In warm antibody hemolytic anemias, opsonized RBCs are removed by the spleen. Reactive oxygen species do not play a role in anemias. Iron is not the rate-limiting step to RBC production when the iron can be recycled within the body.

Question 3 1 / 1 pts A clinical study of patients who inherit mutations that reduce the level of ankyrin, the principal binding site for spectrin, in the RBC membrane cytoskeleton shows an increased prevalence of chronic anemia with splenomegaly. For many patients, it is observed that splenectomy reduces the severity of anemia. This beneficial effect of splenectomy is most likely related to which of the following processes? Decrease in production of reactive oxygen species by splenic macrophages Increase in splenic storage of iron Decrease in opsonization of RBCs and lysis in spleen Decrease in splenic RBC sequestration and lysis Increase in deformability of RBCs within splenic sinusoids

Neurologic injury must be prevented is the correct answer. Although folate and vitamin B12 deficiency both give rise to a macrocytic anemia, a deficiency of vitamin B12 also can result in demyelination of the posterior and lateral columns of the spinal cord. In some cases this deficiency will only be revealed by elevated levels of homocysteine and methylmalonic acid in the serum, because these are more sensitive indicators, particularly earlier in the disease. The anemia caused by vitamin B12 deficiency can be ameliorated by increased administration of folate; this masks the potential neurologic injury by improving the anemia. Treating vitamin B12 deficiency does not improve the anemia caused by folate deficiency, however. An aplastic anemia is unlikely to result from a nutritional deficiency. Folate has no cofactor for absorption, but vitamin B12 must be complexed to intrinsic factor and secreted by gastric parieta

Question 30 1 / 1 pts A clinical study is performed to assess outcomes in patients who have macrocytic anemias as a result of Vitamin 12 or folate deficiency. A comparison of laboratory testing strategies shows that the best strategy includes testing for serum homocysteine, methylmalonic acid, vitamin B12 (cobalamin), and folate. What is the most important reason for ordering these tests simultaneously? Aplastic anemia can result from lack of either nutrient Both nutrients are absorbed similarly Neurologic injury must be prevented Therapy for one deficiency also treats the other Life-threatening thrombocytopenia can occur in both

Vitamin B12 deficiency is the correct answer. The high MCV indicates a marked macrocytosis, greater than expected from reticulocytosis alone. The two best-known causes for such an anemia (also known as megaloblastic anemia when characteristic megaloblastic precursors are seen in the bone marrow) are vitamin B12 and folate deficiency. Because vitamin B12 complexed with intrinsic factor is absorbed in the terminal ileum, its removal can cause vitamin B12 deficiency. Anemia of chronic disease is generally a normocytic anemia. Chronic blood loss and iron deficiency produce a microcytic pattern of anemia, as does dietary iron deficiency. Hemolytic anemia is unlikely several weeks after blood transfusion. Inflammatory bowel diseases (e.g., Crohn disease) increase the risk of malignancy, but myelophthisic anemias (from space-occupying lesions of the marrow) are usually normocytic to mildly macrocytic (from reticulocytosis)

Question 31 1 / 1 pts A 37-year-old woman has experienced abdominal pain and intermittent low-volume diarrhea for the past 3 months. On physical examination, she is afebrile. A stool sample is positive for occult blood. A colonoscopy is performed, and biopsy specimens from the terminal ileum and colon show microscopic findings consistent with Crohn disease. She does not respond to medical therapy, and part of the colon and terminal ileum are removed. She is transfused with 2 U of packed RBCs during surgery. Three weeks later, she appears healthy, but complains of easy fatigability. On investigation, CBC findings show hemoglobin of 10.6 g/dL, hematocrit of 31.6%, RBC count of 2.69 million/μL, MCV of 118 μm3, platelet count of 378,000/mm3, and WBC count of 9800/mm3. The reticulocyte count is 0.3%. Which of the following is most likely to produce these hematologic findings? Hemolytic anemia Vitamin B12 deficiency Chronic blood loss Myelophthisic anemia Anemia of chronic disease

Correct answer is extravascular hemolysis caused by cold agglutinins. The findings point to Coombs-positive immune hemolytic anemia with indirect hyperbilirubinemia. Cold agglutinin immunohemolytic anemia can be seen with lymphoid neoplasms and infections such as Mycoplasma, Epstein-Barr virus, HIV, influenza virus, and cytomegalovirus (CMV). IgM binds to RBCs at cooler peripheral body regions and then fixes complement. At warmer central regions, the antibody is eluted, but the complement marks the RBCs for extravascular destruction in the spleen, but there is minimal intravascular hemolysis. The increased RBC turnover increases the MCV and the bilirubin, which is mainly indirect. Chemotherapy can suppress bone marrow production, but more likely all cell lines, and without an immune component. Although this patient has CMV infection, CMV hepatitis would likely increase direct and indirect bilirubin, and not account

Question 9 1 / 1 pts A 65-year-old man diagnosed with follicular non-Hodgkin lymphoma is treated with chemotherapy. He develops fever and cough of a week's duration. On examination, there are bilateral pulmonary rales. A chest radiograph shows diffuse interstitial infiltrates. A sputum specimen is positive for cytomegalovirus. He develops scleral icterus and Raynaud phenomenon. Laboratory studies show hemoglobin, 10.3 g/dL; hematocrit, 41.3%; MCV, 101 μm3; WBC count, 7600/mm3; and platelet count, 205,000/mm3. His serum total bilirubin is 6 mg/dL, direct bilirubin is 0.8 mg/dL, and LDH is 1020 U/L. Coombs test is positive. Which of the following is the most likely mechanism for his anemia? Marrow aplasia caused by chemotherapy Extravascular hemolysis caused by cold agglutinins Iron deficiency caused by metastases to colon Megaloblastic anemia caused by folate deficiency Vitamin K deficiency caused by cytomegalovirus hepatitis