Ch 14 Robbins Flashcards
For the past 6 months, a 35-year-old woman has experienced an excessively heavy menstrual flow each month. She also has noticed increasing numbers of pinpoint hemorrhages on her lower extremities in the past month. Physical examination shows no organomegaly or lymphadenopathy. CBC shows hemoglobin of 14.2 g/dL, hematocrit of 42.5%, MCV of 91 μm3, platelet count of 19,000/mm3, and WBC count of 6950/mm3. On admission to the hospital, she has melena and is given a transfusion of platelets, but her platelet count does not increase. An emergency splenectomy is performed, and her platelet count increases. Which of the following describes the most likely basis for her bleeding tendency?
□ (A) Abnormalities in production of platelets by megakaryocytes
□ (B) Suppression of pluripotent stem cells
□ (C) Destruction of antibody-coated platelets by the spleen
□ (D) Excessive loss of platelets in menstrual blood
□ (E) Defective platelet-endothelial interactions
(C)
This patient’s bleeding tendency is caused by a low platelet count. She most likely has idiopathic thrombocytopenic purpura (ITP), in which platelets are destroyed in the spleen after being coated with antibodies to platelet membrane glycoproteins IIb-IIIa or Ib-IX affecting both the patient’s platelets and the transfused platelets. Because the spleen is the source of the antibody and the site of destruction, splenectomy can be beneficial. There is no defect in the production of platelets. Suppression of pluripotent stem cells gives rise to aplastic anemia, which is accompanied by pancytopenia. Platelet functions are normal in ITP. Chronic blood loss would not lead to thrombocytopenia when normal bone marrow function is present. Abnormal platelet-endothelial interactions are more likely to cause thrombosis.
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 test result. Direct and indirect Coombs test results are positive at 4°C, although not at 37°C. Which of the following substances on the surfaces of the RBCs most likely accounts for these findings?
□ (A) IgE □ (B) Complement C3b □ (C) Histamine □ (D) IgG □ (E) Fibronectin
(B)
This patient has cold agglutinin disease, with antibody (usually IgM) coating RBCs. The IgM antibodies bind to the RBCs at low temperature and fix complement; however, complement is not lytic at this temperature. With an increase in temperature, 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, because the coating of complement C3b acts as an opsonin. 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. IgE is present in allergic conditions, and histamine is released in type I hypersensitivity reactions. IgG is typically involved in warm antibody hemolytic anemia, which is chronic and is not triggered by cold. Fibronectin is an adhesive cell surface glycoprotein that aids in tissue healing.
A 45-year-old woman has experienced malaise with nausea and vomiting for 3 months. On physical examination, she has scleral icterus and a yellowish hue to her skin. She has difficulty remembering three objects after 3 minutes. There are no neurologic deficits. Laboratory studies show a positive serologic test result for hepatitis C, a serum ALT of 310 U/L, AST of 275 U/L, total bilirubin of 7.6 mg/dL, direct bilirubin of 5.8 mg/dL, alkaline phosphatase of 75 U/L, and ammonia of 55 μmol/L. An abnormal result of which of the following laboratory studies of hemostatic function is most likely to be reported?
□ (A) Immunoassay for plasma von Willebrand factor □ (B) Platelet count □ (C) Prothrombin time □ (D) Fibrin split products □ (E) Platelet aggregation
(C)
This patient has hepatitis C with severe hepatocyte damage. Many of the clotting factors that are instrumental in the in vitro measurement of the extrinsic pathway of coagulation, as measured by the prothrombin time, are synthesized in the liver. Von Willebrand factor is produced by endothelial cells, not hepatocytes. The platelet count is not affected directly by liver disease. Increased fibrin split products suggest a consumptive coagulopathy, such as disseminated intravascular coagulation. Platelet aggregation is a measure of platelet function, which is not significantltly affected by liver disease.
A 25-year-old woman has a 3-year history of arthralgias. Physical examination shows no joint deformity, but she appears pale. Laboratory studies show total RBC count of 4.7 million/mm3, hemoglobin of 12.5 g/dL, hematocrit of 37.1%, platelet count of 217,000/mm3, and WBC count of 5890/mm3. The peripheral blood smear shows hypochromic and microcytic RBCs. Total serum iron and ferritin levels are normal. Hemoglobin electrophoresis shows an elevated hemoglobin A 2 level of about 5.8%. What is the most likely diagnosis?
□ (A) Autoimmune hemolytic anemia □ (B) β-Thalassemia minor □ (C) Infection with Plasmodium vivax □ (D) Anemia of chronic disease □ (E) Iron deficiency anemia
(B)
Although β-thalassemia minor and iron deficiency anemia are characterized by hypochromic and microcytic RBCs, there is no increase in hemoglobin A2 in iron deficiency states. A normal serum ferritin level also excludes iron deficiency. In contrast to β-thalassemia major, there is usually a mild anemia without major organ dysfunction. Diseases that produce hemolysis and increase erythropoiesis (e.g., autoimmune hemolytic anemia, malaria) do not alter the composition of β- globin chain production. Anemia of chronic disease may mimic iron deficiency and thalassemia minor with respect to hypochromia and microcytosis; however, anemia of chronic disease is associated with an increase in the serum concentration of ferritin.
A 30-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 spherocytosis. The circulating RBCs show an increased osmotic fragility. An inherited abnormality in which of the following RBC components best accounts for these findings?
□ (A) Glucose-6-phosphate dehydrogenase □ (B) Membrane cytoskeletal protein □ (C) α-Globin chain □ (D) Heme □ (E) β-Globin chain □ (F) Carbonic anhydrase
(B)
Spectrin and related proteins (e.g., protein 4.1, ankyrin) are cytoskeletal proteins that are important in maintaining the RBC shape. Hereditary spherocytosis is a condition in which a mutation affects one of several membrane cytoskeletal proteins, such as 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. Cells with such mutant proteins are less deformable. The abnormal RBCs seem to lack central pallor on a peripheral blood smear, and they are sequestered and destroyed in the spleen. Glucose-6-phosphate dehydrogenase deficiency is an X-linked condition that most commonly affects black males. 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 buffering capacity.
A 69-year-old, previously healthy woman has been feeling increasingly tired and weak for 4 months. On physical examination, she is afebrile. There is no hepatosplenomegaly or lymphadenopathy. Laboratory studies show hemoglobin of 9.3 g/dL, platelet count of 250,600/mm3, and WBC count of 6820/mm3. The appearance of the peripheral blood smear is shown in the figure. Which of the following conditions should be suspected as the most likely cause of these findings?
□ (A) Pernicious anemia □ (B) Gastrointestinal blood loss □ (C) Aplastic anemia □ (D) β-Thalassemia major □ (E) Warm autoimmune hemolytic anemia
(B)
The RBCs display hypochromia and microcytosis, consistent with iron deficiency. The most common cause of this in elderly patients is chronic blood loss that originates from a gastrointestinal source (e.g., carcinoma, ulcer disease). At age 69, this patient is not menstruating, and vaginal bleeding is likely to be noticed as a “red flag” for a gynecologic malignancy. Pernicious anemia from vitamin B12 deficiency would result in a macrocytic anemia. The RBCs are generally normocytic in patients with aplastic anemia. Microcytosis may accompany thalassemias, but the patient would be unlikely to live to the age of 69 years with β-thalassemia major. Autoimmune hemolytic anemias usually produce a normocytic anemia, or the MCV can be slightly elevated, with a brisk reticulocytosis.
A 76-year-old woman notices that small, pinpoint-to-blotchy areas of superficial hemorrhage have appeared on her gums and on the skin of her arms and legs over the past 3 weeks. On physical examination, she is afebrile and has no organomegaly. Laboratory studies show a normal prothrombin time and partial thromboplastin time. CBC shows hemoglobin of 12.7 g/dL, hematocrit of 37.2%, MCV of 80 μm3, platelet count of 276,000/mm3, and WBC count of 5600/mm3. Platelet function studies and fibrinogen level are normal, and no fibrin split products are detectable. Which of the following conditions best explains these findings?
□ (A) Macronodular cirrhosis □ (B) Chronic renal failure □ (C) Meningococcemia □ (D) Vitamin C deficiency □ (E) Metastatic carcinoma
(D)
Platelet number and function in this case are normal, and there is no detectable abnormality in the extrinsic or intrinsic pathways of coagulation as measured by the prothrombin time or partial thromboplastin time. Petechiae and ecchymoses can result from increased vascular fragility, a consequence of nutritional deficiency (e.g., vitamin C), infection (e.g., meningococcemia), and vasculitic diseases. Liver disease would affect the prothrombin time. Chronic renal failure may depress platelet function. Meningococcemia is an acute illness. Metastatic disease does not directly affect hemostasis, although extensive marrow metastases could diminish platelet production.
A 65-year-old man diagnosed with follicular non-Hodgkin’s lymphoma is treated with chemotherapy. He develops fever and cough. On examination, there are bilateral pulmonary rales. A chest radiograph shows diffuse interstitial infiltrates. A shell vial assay of sputum is positive for cytomegalovirus. He develops scleral icterus. 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’s test is positive. Which of the following is the most likely mechanism for his anemia?
□ (A) Binding of IgM to red blood cells □ (B) Chemotherapeutic bone marrow toxicity □ (C) Cytomegalovirus hepatitis □ (D) Dietary folate deficiency □ (E) Metastases to colon
(A)
The findings point to Coombs-positive immune hemolytic anemia. Cold agglutinin immunohemolytic anemia can be seen with lymphoid neoplasms and infections such as Mycoplasma, Epstein-Barr virus, HIV, influenza virus, and cytomegalovirus. IgM binds to RBCs at cooler peripheral body regions, then fixes complement. At warmer central regions, the antibody is eluted, but the complement marks the RBCs for extravascular destruction in the spleen, and 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. This patient has CMV infection, but hepatitis would likely increase direct and indirect bilirubin, and not account for anemia. Folate deficiency could account for macrocytosis, but not a positive Coombs test. Non-Hodgkin lymphomas do not often involve colon, but this might account for gastrointestinal bleeding with features of iron deficiency and microcytosis.
A 29-year-old woman has had malaise and a low-grade fever for the past week. On physical examination, she appears very pale. 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?
□ (A) Development of anti-RBC antibodies
□ (B) Disseminated intravascular coagulation
□ (C) Accelerated extravascular hemolysis in the spleen
□ (D) Reduced erythropoiesis from parvovirus infection
□ (E) Superimposed iron deficiency
(D)
This patient has 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 RBC production is shut down by parvovirus, 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 RBC antibodies. Iron deficiency does not occur in hemolytic anemias because the iron that is released from hemolyzed cells is reused.
A 60-year-old man has developed widespread ecchymoses over the skin in the past month. His medical history includes a diagnosis of mucinous adenocarcinoma of the rectum. On physical examination, he appears cachectic and pale. An abdominal CT scan shows multiple hepatic masses. Laboratory studies show prothrombin time of 30 seconds, partial thromboplastin time of 55 seconds, platelet count of 15,200/mm3, and fibrinogen level of 75 mg/dL, and fibrin split product levels (D dimer) that are very elevated. Which of the following morphologic findings is most likely to be present on examination of his peripheral blood smear?
□ (A) Howell-Jolly bodies □ (B) Teardrop cells □ (C) Macro-ovalocytes □ (D) Schistocytes □ (E) Target cells
(D)
This is an example of disseminated intravascular coagulation (DIC) with associated microangiopathic hemolytic anemia. The DIC developed in the setting of a mucin-secreting adenocarcinoma. Howell-Jolly bodies are small, round inclusions in RBCs that appear when the spleen is absent. Teardrop cells are most characteristic of myelofibrosis and other infiltrative disorders of the marrow. Macro-ovalocytes are seen in megaloblastic anemias, such as vitamin B12 deficiency. Target cells appear in hemoglobin C disease or severe liver disease.
A 30-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 11.8 g/dL and hematocrit of 35.1%. 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?
□ (A) Infectious mononucleosis □ (B) Mycoplasma pneumoniae infection □ (C) Hereditary spherocytosis □ (D) Escherichia coli septicemia □ (E) Systemic lupus erythematosus
(E)
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. Some are caused by drugs such as α-methyldopa. 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. Infections such as mononucleosis and Mycoplasma are associated with cold autoimmune hemolytic anemia (with an elevated cold agglutinin titer). The increased RBC destruction in hereditary spherocytosis is extravascular and not immune mediated. Septicemia is more likely to lead to a microangiopathic hemolytic anemia.
A 23-year-old woman has had a history of bleeding problems all of her life, primarily heavy menstruation and bleeding gums. A sister and an uncle also have bleeding problems. Physical examination shows several bruises ranging in color from red to blue to purple on her arms and legs. There is no organomegaly, and no deformities are noted. Laboratory studies show hemoglobin, 9.5 g/dL; hematocrit, 28.2%; platelet count, 229,300/mm3; WBC count, 7185/mm3; prothrombin time, 12 seconds; and partial thromboplastin time, 38 seconds. A 1 : 1 dilution of the patient’s plasma with normal pooled plasma corrects the partial thromboplastin time. Ristocetin-dependent platelet aggregation in patient plasma is markedly reduced. Factor VIII activity is 30% (reference range 50% to 150%). Which of the following responses should the physician use when advising the patient of potential consequences of this disease?
□ (A) You might need allogeneic bone marrow transplantation
□ (B) Expect increasing difficulty with joint mobility
□ (C) Anticoagulation is needed to prevent deep venous thrombosis
□ (D) You could experience excessive bleeding after oral surgery
□ (E) A splenectomy might be necessary to control the disease
(D)
An inherited bleeding disorder with normal platelet count and prolonged bleeding time suggests von Willebrand disease, confirmed by the ristocetin-dependent bioassay for von Willebrand factor (vWF). Von Willebrand disease is a common bleeding disorder, with an estimated frequency of 1%. In most cases, it is inherited as an autosomal dominant trait. In these cases, a reduction in the quantity of vWF impairs platelet adhesion to damaged vessel walls, and hemostasis is compromised. Because vWF acts as a carrier for factor VIII, the level of this procoagulant protein (needed for the intrinsic pathway) is diminished, as in this case. The levels of factor VIII rarely are reduced enough, however, to be clinically significant. Prolonged partial thromboplastin time corrected by normal plasma is a reflection of factor VIII deficiency. Because the disease is not a disorder of stem cells, transplantation is not helpful. Joint hemorrhages are a feature of hemophilia A and B, not von Willebrand disease. Patients with von Willebrand disease are not prone to thrombosis, as are individuals with factor V (Leiden) mutation or other inherited disorders of anticoagulation. Splenectomy is useful in cases of idiopathic thrombocytopenic purpura, but the platelets are not consumed in von Willebrand disease.
A 12-year-old boy has a history of episodes of severe abdominal and back pain since early childhood. On physical examination, he is afebrile, and there is no organomegaly. Laboratory studies show hemoglobin of 11.2 g/dL, platelet count of 194,000/mm3, and WBC count of 9020/mm3. The peripheral blood smear shows occasional sickled cells, nucleated RBCs, and Howell-Jolly bodies. Hemoglobin electrophoresis shows 1% hemoglobin A2, 6% hemoglobin F, and 93% hemoglobin S. Hydroxyurea therapy is found to be beneficial in this patient. Which of the following is the most likely basis for its therapeutic efficacy?
□ (A) Increase in production of hemoglobin F
□ (B) Increase in production of hemoglobin A
□ (C) Decrease in overall globin synthesis
□ (D) Stimulation of erythrocyte production
□ (E) Increase in oxygen affinity of hemoglobin
(A) Children and adults with sickle cell anemia may benefit from hydroxyurea therapy, which can increase the concentration of hemoglobin F in RBCs, which interferes with the polymerization of hemoglobin S. However, the therapeutic response to hydroxyurea often precedes the increase in hemoglobin F levels. Hydroxyurea also has an anti- inflammatory effect, increases the mean RBC volume, and can be oxidized by heme groups to produce nitric oxide.Because hemoglobin F levels are high for the first 5 to 6 months of life, patients with sickle cell anemia do not manifest the disease during this period. Because both β-globin chains are affected, no hemoglobin A1 is produced. Globin synthesis decreases with the thalassemias. The hemolysis associated with sickling promotes erythropoiesis, but the concentration of hemoglobin S is not changed. Hydroxyurea does not shift the oxygen dissociation curve or change the oxygen affinity of the various hemoglobins.
A 73-year-old man has been healthy all his life. He takes no medications and has had no major illnesses or surgeries. For the past year, he has become increasingly tired and listless, and he appears pale. Physical examination shows 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. Which of the following is the most likely underlying condition causing this patient’s findings?
□ (A) Occult malignancy □ (B) Autoimmune hemolytic anemia □ (C) β-Thalassemia major □ (D) Chronic alcoholism □ (E) Vitamin B12 deficiency □ (F) Hemophilia A
(A) This patient has a microcytic anemia, which is typical of iron deficiency. Iron deficiency is the most common form of anemia worldwide. 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 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. Thalassemias may result in a microcytosis, but β-thalassemia major causes severe anemia soon after birth, and survival to age 73 years is unlikely. Macrocytosis would accompany a history of chronic alcoholism, probably because of poor diet and folate deficiency. Vitamin B12 deficiency also results in a macrocytic anemia. By this patient’s age, hemophilia A would result in joint problems; because the bleeding is mainly into soft tissues without blood loss, the iron is recycled.
Three days after taking an anti-inflammatory medication that includes phenacetin, a 23-year-old African-American man passes dark reddish brown urine. He is surprised by this 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?
□ (A) α-Thalassemia □ (B) Sickle cell trait □ (C) Glucose-6-phosphate dehydrogenase deficiency □ (D) Autoimmune hemolytic anemia □ (E) β-Thalassemia minor □ (F) RBC membrane abnormality
(C) Glucose-6-phosphate dehydrogenase deficiency 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 also can cause oxidative damage to hemoglobin. Heinz bodies 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 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 with no major problems and no relation to drug usage. Some autoimmune hemolytic anemias can be drug related, but the hemolysis is predominantly extravascular. RBC membrane abnormalities, such as hereditary spherocytosis (caused by abnormal spectrin), typically produce a mild anemia without significant hemolysis, and there is no drug sensitivity.
A 50-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, 11.2 g/dL; hematocrit, 33.3%; 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. The ANA test result is positive. Which of the following is the most likely diagnosis?
□ (A) Iron deficiency anemia □ (B) Aplastic anemia □ (C) Anemia of chronic disease □ (D) Microangiopathic hemolytic anemia □ (E) Megaloblastic anemia □ (F) Thalassemia minor
(C) 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 promote 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. Aplastic anemia is unlikely because the platelet count and WBC count are normal. Microangiopathic hemolytic anemias are caused by serious acute conditions such as disseminated intravascular coagulation; these patients have thrombocytopenia caused by widespread thrombosis. Megaloblastic anemias are macrocytic without an increase in iron stores. Thalassemia minor is uncommon and is not associated with a positive ANA test result.
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, a subset of individuals of this ancestry are found to have increased hemoglobin S levels. The distribution of infectious illnesses is correlated with the prevalence of hemoglobin S in this population. Which of the following infectious agents is most likely to account for these observations?
□ (A) Cryptococcus neoformans □ (B) Borrelia burgdorferi □ (C) Treponema pallidum □ (D) Plasmodium falciparum □ (E) Clostridium perfringens □ (F) Trypanosoma gambiense □ (G) Schistosoma haematobium
(D) Throughout human history, malaria has been the driving force for increasing the gene frequency of hemoglobin S. Individuals who are heterozygous for hemoglobin S have the sickle cell trait. They are resistant to malaria 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 cannot complete its life cycle. Clostridium neoformans can cause granulomatous disease in immunocompromised individuals. Borrelia burgdorferi is the spirochete that causes Lyme disease. Treponema pallidum is the infectious agent causing syphilis. Clostridium perfringens may produce gas gangrene after soft-tissue injuries. Trypanosoma gambiense infection causes sleeping sickness. Schistosoma haematobium infection leads to hematuria and iron deficiency anemia.
A 41-year-old woman sees her physician because of 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%. Given these laboratory findings, which of the following historical findings would be most useful in determining the cause of her condition?
□ (A) Exposure to drugs □ (B) Dietary history □ (C) Recent bacterial infection □ (D) Menstrual history □ (E) Family history of anemias
(A) The 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 vitamin B12 deficiency. Menstrual history would be relevant if the patient had hypochromic microcytic anemia. The only known familial cause of aplastic anemia (Fanconi anemia) is rare.
A clinical study of patients with hemoglobinopathies reveals that some of these patients developed episodes of acute chest, back, and abdominal pain; recurrent infections with Streptococcus pneumoniae; and chronic anemia as children and adults. They experienced none of these problems as infants, however. The presence of which of the following types of hemoglobin during infancy most likely provided protection from complications of their hemoglobinopathy?
□ (A) A1 □ (B) A2 □ (C) C □ (D) E □ (E) F
(E) These patients have sickle cell disease with hemoglobin S. During infancy, the amount of fetal hemoglobin being produced is sufficient to prevent most complications of the disease, such as vaso-occlusive crises and infections. After infancy, the amount of hemoglobin F declines, but drugs such as hydroxyurea can induce increased production of hemoglobin F. Hemoglobin A1 is the normal adult hemoglobin that is absent with homozygous sickle cell anemia. Hemoglobin A2 is not produced in sufficient quantities to ameliorate the effects of hemoglobinopathies. Hemoglobins C and E when homozygous produce anemia much milder than hemoglobin S disease, and when heterozygous help ameliorate hemoglobin S, but there is no differential production of hemoglobin C or E in infancy.
A 5-year-old boy has had a history of easy bruising and blood in his urine since infancy. Physical examination shows no organomegaly. He has several ecchymoses of the skin on the lower extremities. Laboratory studies show hemoglobin, 13.1 g/dL; hematocrit, 39.3%; platelet count, 287,600/mm3; WBC count, 6830/mm3; prothrombin time, 13 seconds; partial thromboplastin time, 54 seconds; and less than 1% factor VIII activity measured in plasma. If he does not receive transfusions of recombinant factor VIII concentrate, which of the following manifestations of this illness is most likely to ensue?
□ (A) Splenomegaly □ (B) Conjunctival petechiae □ (C) Hemolysis □ (D) Hemochromatosis □ (E) Hemarthroses
(E) The severity of hemophilia A depends on the amount of factor VIII activity. With less than 1% activity, there is severe disease, and joint hemorrhages are common, leading to severe joint deformity and ankylosis. Mild (1% to 5%) and moderate (5% to 75%) activity is often asymptomatic except in severe trauma. The bleeding tendency is not associated with splenomegaly. Petechiae, seen in patients with thrombocytopenia, are not a feature of hemophilia. Factor VIII deficiency does not affect the life span of RBCs. Because individuals with factor VIII deficiency do not depend on RBC transfusions, iron overload is not a usual consequence
A 23-year-old woman in her 25th week of pregnancy has felt no fetal movement for the past 3 days. Three weeks later, she still has not given birth and suddenly develops dyspnea with cyanosis. On physical examination, her temperature is 36.9°C, pulse is 102/min, respirations are 21/min, and blood pressure is 80/40 mm Hg. She has large ecchymoses over the skin of her entire body. A stool sample is positive for occult blood. Laboratory studies show an elevated prothrombin time and partial thromboplastin time. The platelet count is decreased, plasma fibrinogen is markedly decreased, and fibrin split products are detected. A blood culture is negative. Which of the following is the most likely cause of the bleeding diathesis?
□ (A) Increased vascular fragility
□ (B) Toxic injury to the endothelium
□ (C) Reduced production of platelets
□ (D) Increased consumption of clotting factors and platelets
□ (E) Defects in platelet adhesion and aggregation
(D) The presence of thrombocytopenia, increased prothrombin and partial thromboplastin times, and fibrin split products, and the low fibrinogen concentration all suggest disseminated intravascular coagulation (DIC), which was most likely caused by a retained dead fetus, an obstetric complication that can lead to DIC through release of thromboplastins from the fetus. This release causes widespread microvascular thrombosis and consumes clotting factors and platelets. There is no damage to the vascular endothelium or vascular wall. Platelet production is normal, but platelets are consumed by widespread thrombosis of small vessels. There is no defect in platelet function.
