HEMATOPATHOLOGY OF RED BLOOD CELLS AND BLEEDING DISORDERS

Complement C3b

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?

Glucose-6-phosphate dehydrogenase deficiency

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?

Hemoglobin Bart's

A 32-year-old woman from Hanoi, Vietnam, gives birth at 34 weeks' gestation to a markedly hydropic stillborn male infant. Autopsy findings include hepatosplenomegaly and cardiomegaly, serous effusions in all body cavities, and generalized hydrops. No congenital anomalies are noted. There is marked extramedullary hematopoiesis in visceral organs. Which of the following hemoglobins is most likely predominant on hemoglobin electrophoresis of the fetal RBCs?

Chronic blood loss

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?

Plasmodium falciparum

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?

Granulocytes

A 72-year-old woman undergoes laparotomy for ruptured diverticulitis. A day later her WBC count is elevated and her blood pressure is 85/45 mm Hg. Her peripheral blood smear shows schistocytes. She receives 5 units of fresh frozen plasma. As the 5th unit is being transfused, she develops sudden severe dyspnea and begins coughing up large quantities of frothy sputum. A chest radiograph shows bilateral pulmonary edema. She is most likely to have developed a transfusion reaction to which of the following components of the donor blood product?

Occult malignancy

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 figure. Which of the following is the most likely underlying condition causing this patient's findings?

Myelophthisic anemia

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?

Vitamin C deficiency

A 77-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?

Loss of normal splenic function

A 10-year-old child has experienced multiple episodes of pneumonia and meningitis with septicemia since infancy. Causative organisms include Streptococcus pneumoniae and Haemophilus influenzae. On physical examination, the child has no organomegaly and no deformities. Laboratory studies show hemoglobin of 9.2 g/dL, hematocrit of 27.8%, platelet count of 372,000/mm3, and WBC count of 10,300/mm3. A hemoglobin electrophoresis shows 1% hemoglobin A2, 7% hemoglobin F, and 92% hemoglobin S. Which of the following is the most likely cause of the repeated infections in this child?

Production of hemoglobin F

A 12-year-old boy has a history of episodes of severe abdominal, chest, 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. An increase in which of the following is the most likely basis for its therapeutic efficacy?

X-linked recessive

A 12-year-old boy has had worsening problems with joint mobility involving his arms and legs, particularly his knees and ankles, for the past 6 years. He has been receiving therapy for this condition. His grandfather had a similar condition and died at age 25 years. On physical examination, he has no visible petechiae or areas of purpura. Laboratory studies show that prothrombin time is 12 seconds, and partial thromboplastin time is 52 seconds. After addition of an equivalent aliquot of normal plasma, the partial thromboplastin time is 30 seconds. Hemoglobin is 12.9 g/dL, platelet count is 238,500/mm3, and WBC count is 6620/mm3. His platelet function studies are normal. What is the most likely inheritance pattern for his condition?

Extensive RBC adhesion to endothelium

A 13-year-old boy has the sudden onset of severe abdominal pain and cramping accompanied by chest pain, nonproductive cough, and fever. On physical examination, his temperature is 39° C, pulse is 110/min, respirations are 22/min, and blood pressure is 80/50 mm Hg. He has diffuse abdominal tenderness, but no masses or organomegaly. Laboratory studies show a hematocrit of 18%. The peripheral blood smear is shown in the figure. A chest radiograph shows bilateral pulmonary infiltrates. Which of the following is the most likely mechanism for initiation of his pulmonary problems?

Hemophilia B

A 15-year-old girl has a history of easy bruising and hemorrhages. Since menarche at the age of 13 years, she has had menometrorrhagia. On physical examination, she displays joint deformity and has decreased mobility of the ankles, knees, and wrists. Laboratory studies show hemoglobin, 11.8 g/dL; hematocrit, 35.1%; platelet count, 267,000/mm3; WBC count, 5960/mm3; prothrombin time, 13 seconds; and partial thromboplastin time, 60 seconds. A 1:1 dilution of the patient's plasma with normal pooled plasma corrects the partial thromboplastin time. Which of the following is the most likely diagnosis?

Phosphatidylinositol glycan A (PIGA)

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?

Glanzmann thrombasthenia

A 16-year-old girl has had frequent nosebleeds since childhood. Her gums bleed easily, even with routine tooth brushing. She has experienced menorrhagia since menarche at age 13 years. On physical examination, there are no abnormal findings. Laboratory studies show hemoglobin, 14.1 g/dL; hematocrit, 42.5%; MCV, 90 μm3; platelet count, 277,400/mm3; and WBC count, 5920/mm3. Her platelets fail to aggregate in response to ADP, collagen, epinephrine, and thrombin. The ristocetin agglutination test result is normal. There is a deficiency of glycoprotein IIb/IIIa. Prothrombin time is 12 seconds, and partial thromboplastin time is 28 seconds. What is the most likely diagnosis?

β-Globin

A 17-year-old girl has had a history of fatigue and weakness for her entire life. She has not undergone puberty. On physical examination, secondary sex characteristics are not well developed. She has hepatosplenomegaly. CBC shows hemoglobin of 9.1 g/dL, hematocrit of 26.7%, MCV of 66 μm3, platelet count of 89,000/mm3, and WBC count of 3670/mm3. The appearance of the peripheral blood smear is shown in the figure. Additional laboratory findings include serum glucose of 144 mg/dL, TSH of 6.2 mU/mL, and ferritin of 679 ng/mL. A mutation in a gene encoding for which of the following is most likely to be present in this girl?

Heparin

A 21-year-old woman known to have a protein C deficiency develops recurrent pulmonary thromboembolism and is placed on anticoagulant therapy. Two weeks after initiation of this therapy, she has a sudden change in mental status and experiences difficulty speaking and swallowing. A cerebral angiogram shows a left middle cerebral artery occlusion. Laboratory studies show hemoglobin of 13 g/dL, platelet count of 65,400/mm3, WBC count of 5924/mm3, prothrombin time of 12 seconds, and partial thromboplastin time of 51 seconds. The anticoagulant therapy is discontinued. Which of the following pharmacologic agents used as an anticoagulant in this patient is most likely to have caused these findings?

Plasmodium vivax

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?

Excessive bleeding after oral surgery

A 23-year-old woman has a history of easy bruising. Physical examination shows multiple 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 is the most likely potential consequence of this disease?

Consumption of coagulation factors

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 37° C, pulse is 106/min, respirations are 23/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 her bleeding diathesis?

Mislabeled specimens were processed in the laboratory

A 25-year-old man involved in a motorcycle accident incurs a laceration to his thigh. The bleeding is stabilized en route to the hospital, but on arrival he is noted to have orthostatic hypotension and his hematocrit is 21%. He receives 2 units of PRBCs. As the first unit is nearly finished transfusing, he becomes febrile and hypotensive. Urine output ceases. The serum above the clot in a red top phlebotomy tube is pink. Which of the following complications of transfusion has most likely occurred in this man?

β-Thalassemia minor

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 93% hemoglobin A1 with elevated hemoglobin A2 level of 5.8% and hemoglobin F level of 1.2%. What is the most likely diagnosis?

Spectrin cytoskeletal protein

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?

Hematopoietic stem cell defect

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?

Intravascular disruption

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?

Positive Coombs test

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?

Imbalance in α-globin and β-globin chain production

A 3-year-old boy from Sicily has a poor appetite and is underweight for his age and height. Physical examination shows hepatosplenomegaly. The hemoglobin concentration is 6 g/dL, and the peripheral blood smear shows severely hypochromic and microcytic RBCs. The total serum iron level is normal, and the reticulocyte count is 10%. A radiograph of the skull shows maxillofacial deformities and expanded marrow spaces. Which of the following is the most likely cause of this child's illness?

Microangiopathic hemolytic anemia

A 30-year-old man has had pain and burning on urination for the past week. On physical examination, he is febrile and has a pulse of 92/min, respirations of 18/min, and blood pressure of 80/45 mm Hg. Digital rectal examination indicates that he has an enlarged, tender prostate. There is costovertebral angle tenderness on the right. Scattered ecchymoses are present over the trunk and extremities. Laboratory studies show a blood culture positive for Klebsiella pneumoniae. The appearance of the RBCs in a peripheral blood smear is shown in the figure. Which of the following hematologic disorders is he most likely to have?

Oxidative injury to hemoglobin

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?

Immune-mediated hemolysis

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?

Antiphospholipid syndrome

A 33-year-old woman, G3, P0, who has had two spontaneous abortions, is in the second trimester of her third pregnancy. An ultrasound at 18 weeks' gestation revealed symmetric growth retardation. She gives birth to a stillborn fetus at 25 weeks, and experiences sudden onset of dyspnea. A pulmonary ventilation/perfusion scan indicates a high probability of thromboembolism. Four months later, she experiences an altered state of consciousness and sudden loss of movement in the right arm. A cerebral angiogram shows occlusion of a branch of the left middle cerebral artery. Laboratory findings show hemoglobin, 13.4 g/dL; hematocrit, 40.3%; MCV, 91 μm3; platelet count, 124,000/mm3; WBC count, 5530/mm3; prothrombin time, 13 seconds; partial thromboplastin time, 46 seconds; positive anticardiolipin antibody; positive serologic test result for syphilis; and negative ANA. Which of the following best explains these findings?

Systemic lupus erythematosus

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?

Vitamin B12 deficiency

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?

Destruction of antibody-coated platelets by the spleen

A 37-year-old woman has noted an excessively heavy menstrual flow each of the past 6 months. 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 15,000/mm3, and WBC count of 6950/mm3. On admission to the hospital, she has melena and after a transfusion of platelets, her platelet count does not increase. Which of the following describes the most likely basis for her bleeding tendency?

Anemia of chronic disease

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?

Immune thrombocytopenic purpura

A 42-year-old woman has had nosebleeds, easy bruising, and increased bleeding with her menstrual periods for the past 4 months. On physical examination, her temperature is 37° C, pulse is 88/min, and blood pressure is 90/60 mm Hg. She has scattered petechiae over the distal extremities. There is no organomegaly. Laboratory studies show hemoglobin of 12.3 g/dL, hematocrit of 37%, platelet count of 21,500/mm3, and WBC count of 7370/mm3. A bone marrow biopsy specimen shows a marked increase in megakaryocytes. The prothrombin and partial thromboplastin times are within the reference range. What is the most likely diagnosis?

Exposure to medications

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?

Prothrombin time

A 44-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 269 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?

Inadequate usage of stored iron

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?

Presence of antibodies against ADAMTS13 metalloproteinase

A 45-year-old woman has had episodes of blurred vision and headaches for the past 6 months. She has had worsening confusion with paresthesias over the past 3 days. On physical examination, she has a temperature of 39.6° C, pulse of 100/min, respiratory rate of 20/min, and blood pressure of 80/50 mm Hg. Petechial hemorrhages are noted over her trunk and extremities. Laboratory findings include hemoglobin, 10.9 g/dL; hematocrit, 34%; MCV, 96 μm3; platelet count, 28,000/mm3; and WBC count, 8500/mm3. Fragmented RBCs are noted on her peripheral blood smear. Blood urea nitrogen is 40 mg/dL, and serum creatinine is 3.1 mg/dL. Which of the following is the most likely underlying cause for her findings?

Erythroid hypoplasia

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?

Serum ferritin

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?

Thrombotic thrombocytopenic purpura

A 56-year-old woman suffers the sudden onset of headache and photophobia, and her condition worsens for the next 2 days. On physical examination, she has a temperature of 38° C and is disoriented. CBC shows hemoglobin of 11.2 g/dL, hematocrit of 33.7%, MCV of 94 μm3, platelet count of 32,000/mm3, and WBC count of 9900/mm3. The peripheral blood smear shows schistocytes. The serum urea nitrogen level is 38 mg/dL, and the creatinine level is 3.9 mg/dL. Which of the following is the most likely diagnosis?

Diminished nuclear maturation from impaired DNA synthesis

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?

Extravascular hemolysis caused by cold agglutinins

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?

Antiplatelet antibodies

A 9-year-old boy has developed prominent bruises on his extremities over the past week. On physical examination, he has ecchymoses and petechiae on his arms and legs. Laboratory studies show hemoglobin, 13.8 g/dL; hematocrit, 41.9%; MCV, 93 μm3; platelet count, 11,300/mm3; and WBC count, 7720/mm3. He had respiratory syncytial virus pneumonia 3 weeks ago. His condition improves with corticosteroid therapy. Which of the following abnormalities is most likely to cause his hemorrhagic diathesis?

Thrombotic thrombocytopenic purpura (TTP)

A clinical study is performed involving adult patients diagnosed with microangiopathic hemolytic anemia. A subgroup of patients who had fever or diarrhea preceding the initial diagnosis of anemia were excluded. The patients had schistocytes present on peripheral blood smears. Some of these patients were found to have a deficiency of a metalloproteinase known as ADAMTS13. Which of the following conditions were the patients with this deficiency most likely to have?

Neurologic injury must be prevented

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?

Hepcidin

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?

Decrease in splenic RBC sequestration and lysis

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?

Reticulocytosis

A healthy 19-year-old woman suffered blunt abdominal trauma in a motor vehicle accident. On admission to the hospital, her initial hematocrit was 33%, but over the next hour, it decreased to 28%. A paracentesis yielded serosanguineous fluid. She was taken to surgery, where a liver laceration was repaired, and 1 L of bloody fluid was removed from the peritoneal cavity. She remained stable. A CBC performed 3 days later is most likely to show which of the following morphologic findings in the peripheral blood?

Platelets

A study of transfusion reactions reveals that some patients experienced an increase in body temperature that was greater than 1°C, accompanied by chills and hypotension. Blood cultures are positive for bacterial organisms. These patients respond to antibiotic therapy. Which of the following types of blood products did they most likely receive?

Hemarthroses

An 11-year-old child has a history of easy bruising. At age 9 years, he experienced hemorrhaging around the pharynx that produced acute airway obstruction. Family history indicates that other male relatives have similar bleeding problems. Laboratory studies show hemoglobin, 13.1 g/dL; hematocrit, 39.2%; platelet count, 228,000/mm3; WBC count, 5950/mm3; prothrombin time, 13 seconds; and partial thromboplastin time, 52 seconds. A 1:1 dilution of the patient's plasma with normal pooled plasma corrects the partial thromboplastin time. Which of the following manifestations of this illness is most likely to ensue without therapy?

Reduced erythropoiesis from parvovirus infection

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?

Extensive fibrosis

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?

Hemolysis of antibody-coated cells

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?

Decreased haptoglobin

During the past 6 months, a 25-year-old woman has noticed a malar skin rash that is made worse by sun exposure. She also has had arthralgias and myalgias. On physical examination, she is afebrile and has a pulse of 100/min, respirations of 20/min, and blood pressure of 100/60 mm Hg. There is erythema of skin over the bridge of the nose. No organomegaly is noted. Laboratory findings include positive serologic test results for ANA and double-stranded DNA, hemoglobin of 8.1 g/dL, hematocrit of 24.4%, platelet count of 87,000/mm3, and WBC count of 3950/mm3. The peripheral blood smear shows nucleated RBCs. A dipstick urinalysis is positive for blood, but there are no WBCs, RBCs, or casts seen on microscopic examination of the urine. Which of the following laboratory findings is most likely to be present?

Telomerase

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?

Plasmodium falciparum

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?

Splice site

Since childhood, a 30-year-old man has been easily fatigued with minimal exercise. Laboratory studies show hypochromic microcytic anemia. Hemoglobin electrophoresis reveals decreased Hgb A1 with increased Hgb A2 and Hgb F. His serum ferritin is markedly increased. Which of the following mutations is most likely to be present in the β-globin gene of this man?

Hemoconcentration

Soon after crossing the finish line in a 10-km race, a 31-year-old man collapses. On physical examination, his temperature is 40.1° C, pulse is 101/min, respirations are 22/min, and blood pressure is 85/50 mm Hg. He is not perspiring, and his skin shows decreased turgor. Laboratory studies show Na+, 155 mmol/L; K+, 4.6 mmol/L; Cl−, 106 mmol/L; CO2, 27 mmol/L; glucose, 68 mg/dL; creatinine, 1.8 mg/dL; hemoglobin, 20.1 g/dL; hematocrit, 60.3%; platelet count, 230,400/mm3; and WBC count, 6830/mm3. What is the most likely diagnosis?