Hematology Questions and Answers 

Chapter:
Hematology Questions and Answers
Author(s):
Robert D. Ficalora
DOI:
10.1093/med/9780199985876.003.0009
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Questions
Multiple Choice (choose the best answer)

Anemias and Myeloid Malignancies

1. A 67-year-old man is evaluated for exertional dyspnea. He recalls that 3 years ago he was told that he
had anemia. In reviewing his records, you note that at that time his hemoglobin level was 9.5 g/dL and his
hematocrit was 33% with an increased mean corpuscular volume (MCV); the remainder of his complete
blood cell count was normal. On physical examination, he had conjunctival pallor, normal heart and lung
findings, no lymphadenopathy, no hepatomegaly or splenomegaly, and no petechiae or ecchymoses.
Diagnostic testing results are shown in Table 9.Q1.

Table 9.Q1

Component Finding

Hemoglobin, g/dL 7.5

Hematocrit, % 23

Mean corpuscular volume, fL 110 (reference range, 86–98)

Leukocyte count, ×10 /L 9

2.1
Neutrophils, % 20
Lymphocytes, % 70
Monocytes, % 6
Basophils, % 3
Eosinophils, % 1

Platelet count, ×10 /L

9
64

Reticulocyte count, % of erythrocytes 0.3 (reference range, 0.5–1.5)

Absolute reticulocyte count, ×10 /L9

10.0 (reference range, 29.5–87.3)
 Component Finding

Peripheral blood film Dimorphic erythrocyte population with pronounced macrocytes

Lactate dehydrogenase, U/L 150 (reference range, 140–280)

Which of the following is the most likely explanation for these findings?

1. a. Acute myeloid leukemia (AML)

2. b. Vitamin B12 deficiency
3. c. Hemolytic anemia
4. d. Myelodysplastic syndrome (MDS)
5. e. Primary myelofibrosis
2. A 45-year-old woman is admitted to the surgical service with severe arterial insufficiency of the right
second toe. She has no prior medical history and takes no medications. Physical examination findings are
normal except for mild splenomegaly and signs of early gangrene in the right second toe. All pulses are
full and equal throughout. Diagnostic testing results are shown in Table 9.Q2.

Table 9.Q2

Component Finding

Hemoglobin, g/dL 13.2

Hematocrit, % 39

Leukocyte count, ×10 /L 9

15.5
Segmented neutrophils, % 78
Band cells, % 4
Lymphocytes, % 20
Monocytes, % 5
Basophils, % 2
Eosinophils, % 1

Platelet count, ×10 /L

9
1,300

Mean corpuscular volume, fL 88

Erythrocyte sedimentation 28
rate, mm/h

Leukocyte alkaline 110 (reference range, 13–130)

phosphatase score

Serum ferritin Within reference range

 Component Finding

Serum iron Within reference range

Serum total iron-binding Within reference range

capacity

Peripheral blood film Increased large platelets with some clustering; leukocytes and erythrocytes
are unremarkable

Bone marrow aspiration and Increased cellularity with increased and atypical megakaryocytes in
biopsy clusters; reticulin staining is normal

Chromosomal analysis Normal female karyotype (46XY)

Which of the following is the most likely diagnosis?

1. a. Essential thrombocythemia
2. b. Vasculitis
3. c. Philadelphia chromosome–negative chronic myeloid leukemia (CML)
4. d. Primary myelofibrosis (PMF)
3. A 22-year-old man is admitted to the hospital for an elective cholecystectomy. You are asked to see
him because he had anemia on preoperative testing. He tells you that he has always been told by his
physicians that he has mild anemia; his medical history is otherwise unremarkable. His vital signs are
normal. His conjunctivae are mildly icteric, and the spleen is palpable in the left upper quadrant. Findings
on the remainder of the physical examination are normal. Diagnostic testing results are shown in
Table 9.Q3.

Table 9.Q3

Component Finding

Hemoglobin, g/dL 11.2

Hematocrit, % 34

Leukocyte count, ×10 /L 9

9.0
Differential count Within reference ranges

Platelet count, ×10 /L9

295

Mean corpuscular volume, fL 89

Reticulocyte count, % 4

Absolute reticulocyte count, ×10 /L 9

200 (reference range, 29.5–87.3)
 Component Finding

Peripheral blood film Polychromasia with numerous microspherocytes

Which of the following tests would most likely help confirm the diagnosis?

1. a. Hemoglobin electrophoresis
2. b. Osmotic fragility test
3. c. Direct and indirect antiglobulin (Coombs) tests
4. d. Bone marrow aspiration and biopsy
4. A 28-year-old black man with sickle cell disease presents to the emergency department with abdominal
pain, chest pain, and shortness of breath. His dyspnea evolved over 36 hours after a visit with his niece
and nephew. His history is significant for approximately 2 emergency department visits or hospital
admissions per year for painful crises. Three years ago, he spent 4 weeks in the hospital after an episode
of acute chest syndrome. He has been taking hydroxyurea but only intermittently because of financial
concerns. His pulse is 116 beats per minute and regular, his blood pressure is 138/76 mm Hg, his
respiratory rate is 18 breaths per minute, and his temperature is 38.3°C. Pulse oximetry shows 91%
oxygen saturation with room air and 93% with 4 L of oxygen by nasal cannula. His lungs have scattered
inspiratory crackles in the right midlung field. His spleen is not palpable. The remainder of the physical
examination findings are normal. Diagnostic testing results are shown in Table 9.Q4.

Table 9.Q4

Component Finding

Hemoglobin, g/dL 7.9

Hematocrit, % 25

Mean corpuscular volume, fL 80

Leukocyte count, ×10 /L 9

16.0
Segmented neutrophils, % 70
Band cells, % 7
Lymphocytes, % 15
Monocytes, % 5
Basophils, % 2
Eosinophils, % 1

Platelet count, ×10 /L

9
490

Creatinine, mg/dL 1.4

Peripheral blood film Anisopoikilocytosis with multiple sickle cells

A chest radiograph shows a right middle and upper lobe air space infiltrate. The patient is given
supplemental oxygen, adequate pain control, and intravenous antibiotics. Which of the following should
you now order?
1. a. Hydroxyurea
2. b. Erythrocyte exchange transfusion
3. c. Plasma exchange
4. d. Anticoagulation with unfractionated heparin
5. e. Aggressive intravenous fluid hydration
5. A 70-year-old man presents with weakness of his right arm and leg. His symptoms began yesterday
and are now resolved. He also reports a 6-month history of recurrent headaches and fatigue. He is a
nonsmoker. His medical history is significant for high blood pressure. His blood pressure is 167/88 mm
Hg, his oxygen saturation is 93% on room air, his face is plethoric, and a right carotid bruit is heard. Other
findings on physical examination are normal. Diagnostic testing results are shown in Table 9.Q5.

Table 9.Q5

Component Finding

Hemoglobin, g/dL 20.5

Hematocrit, % 58

Mean corpuscular volume, fL 88

Leukocyte count, ×10 /L 9

12.5
Neutrophils, % 83
Lymphocytes, % 12
Monocytes, % 3
Basophils, % 2

Platelet count, ×10 /L9

600

Erythropoietin, mIU/mL <2 (reference range, 0–19)

Carotid ultrasonography shows a 30% stenotic lesion in the right carotid. The patient is hospitalized and
begins antiplatelet therapy. Which of the following should you order next?

1. a. JAK2 V617F mutation testing

2. b. Fluorescence in situ hybridization (FISH) for BCR-ABL testing
3. c. Arterial blood gas analysis
4. d. Bone marrow aspiration and biopsy
6. A 42-year-old woman with a history of systemic lupus erythematosus (SLE) presents with fatigue. She
has been receiving anti–tumor necrosis factor therapy and has been managing the SLE well. However,
she has recently experienced worsening fatigue. Her vital signs are normal. Her face and conjunctivae
are jaundiced, and she has a fading butterfly rash on her face. The spleen is palpable on deep inspiration.
Diagnostic testing results are shown in Table 9.Q6, and the peripheral blood film is shown in Figure 9.Q6.

Table 9.Q6

Component Finding

Hemoglobin, g/dL 7.8

 Component Finding

Hematocrit, % 27

Mean corpuscular volume, fL 95

Leukocyte count, ×10 /L 9

4.5
Differential count Within reference ranges

Platelet count, ×10 /L

9
450

Reticulocyte count, % 4

Absolute reticulocyte count, ×10 /L 9

170.0 (reference range, 29.5–87.3)

Erythrocyte sedimentation rate, mm/h 25

Lactate dehydrogenase, U/L 400 (reference range, 140–280)

Total bilirubin, mg/dL 3.5 (reference range, 0.1–1.0)

Indirect bilirubin, mg/dL 3.0

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Figure 9.Q6
Which of the following is the best interpretation of these data?

1. a. The hemolysis is predominantly intravascular.

2. b. The bone marrow is not responding to the anemia.
3. c. Direct Coombs testing results should be positive.
4. d. Urine hemoglobin testing results should be positive.
7. A 58-year-old woman with active rheumatoid arthritis presents with fatigue and joint pain. She received
the diagnosis of rheumatoid arthritis 5 years earlier and has been taking prednisone 10 mg daily and
methotrexate with folate weekly. She has had chronic fatigue and anemia. Her vital signs are normal. Her
conjunctivae are pale, and she has active synovitis affecting both knees, her wrists, and elbows, with
rheumatoid nodules on the extensor surface of her right forearm. The remainder of the physical
examination findings are normal. Diagnostic testing results are shown in Table 9.Q7.

Table 9.Q7

Component Finding

Hemoglobin, g/dL 9.0

Hematocrit, % 30

Mean corpuscular volume, fL 80

Leukocyte count, ×10 /L 9

11.5
Neutrophils, % 90
Lymphocytes, % 8
Monocytes, % 2

Platelet count, ×10 /L

9
500

Erythrocyte sedimentation rate, mm/h 50

Erythropoietin, mIU/mL 15 (reference range, 0–19)

Which of the following laboratory findings are consistent with this condition?

1. a. Elevated hepcidin, elevated ferritin, elevated total iron-binding capacity (TIBC), elevated
serum iron
2. b. Elevated hepcidin, elevated ferritin, decreased TIBC, elevated serum iron
3. c. Decreased hepcidin, elevated ferritin, decreased TIBC, elevated serum iron
4. d. Elevated hepcidin, elevated ferritin, decreased TIBC, normal serum iron
5. e. Decreased hepcidin, elevated ferritin, elevated TIBC, normal serum iron
Coagulation

8. A 62-year-old man underwent right total knee replacement 8 days ago. Swelling has developed in his
right lower extremity, and Doppler ultrasonography confirms the presence of a right superficial femoral
vein thrombosis. His current medications include oxycodone and subcutaneous unfractionated heparin.
Results of preoperative tests, including a complete blood cell count and liver and kidney function, were
normal. Other laboratory data include the following: hemoglobin 12.2 g/dL, leukocyte count 8.5×10 9/L, and
platelet count 60×109/L. In addition to stopping the use of subcutaneous heparin, what is the next most
appropriate step in management of this patient?

1. a. Start low-molecular-weight heparin therapy.

2. b. Start intravenous therapeutic doses of heparin.
3. c. Start direct thrombin inhibitor therapy.
4. d. Start aspirin therapy.
9. A 45-year-old man presents with deep vein thrombosis of the right femoral vein. Three months ago, he
received a diagnosis of systemic lupus erythematosus (SLE). In addition to confirming SLE, laboratory
testing also documented the presence of a lupus anticoagulant (LAC). There is no family history of
venous thrombosis. Current medications include hydroxychloroquine. Laboratory testing shows normal
results for a complete blood cell count and for tests of liver and kidney function. Special coagulation
testing confirms the persistence of an LAC. What is the most reasonable duration of warfarin
anticoagulation for this patient?

1. a. 3 months
2. b. 1 year
3. c. 6 months
4. d. Long-term
5. e. 6 weeks
10. A 20-year-old white woman has been admitted to the hospital with pulmonary embolism. She has no
chronic illnesses and is receiving no medications except for combination estrogen-progesterone birth
control pills that she started using approximately 1 year earlier. Results were normal for a complete blood
cell count, baseline prothrombin time, activated partial thromboplastin time (aPTT), and tests of kidney
and liver function. The patient is currently receiving therapeutic doses of intravenous unfractionated
heparin, and her aPTT is therapeutic at 72 seconds. A panel of thrombophilia tests has been performed.
Which of the following statements about her thrombophilia test results is correct?

1. a. DNA-based testing for factor V Leiden and prothrombin G20210A mutations are reliable.

2. b. Low antithrombin confirms a hereditary deficiency state.
3. c. A positive result on lupus anticoagulant (LAC) testing confirms antiphospholipid antibody
syndrome.
4. d. Low protein S confirms the presence of a hereditary deficiency state.
11. A 62-year-old man with chronic atrial fibrillation has been treated with warfarin. He has no other
chronic illnesses and is receiving no other medications long-term except for lipid-lowering agents. Results
of his complete blood cell count and tests of renal and kidney function are normal. He checks his
prothrombin time monthly and has kept the international normalized ratio (INR) within the therapeutic
range (2–3) for the duration of his therapy with warfarin. He has heard about recent US Food and Drug
Administration (FDA) approval of dabigatran, which requires no monitoring, and he would like a
prescription for this new drug. Which of the following statements is true about the use of dabigatran in
atrial fibrillation compared with the well-managed use of warfarin?

1. a. Switching to dabigatran would result in superior outcomes.

2. b. Switching to dabigatran would result in inferior outcomes.
3. c. Switching to dabigatran would provide no significant benefit.
4. d. Dabigatran is FDA approved for postoperative thromboprophylaxis for knee and hip
replacement surgery.
5. e. Dabigatran is FDA approved as an anticoagulant for patients who have received a
mechanical heart valve.
12. A 22-year-old woman is brought to the emergency department after having 1 witnessed tonic-clonic
seizure. She had appeared confused for the preceding few hours. On examination, she is febrile and
appears slightly confused; otherwise, neurologic and physical examination findings are normal.
Laboratory testing results are shown in Table 9.Q12, and the peripheral blood smear is shown in
Figure 9.Q12.

Table 9.Q12

Component Finding Reference Range

Hemoglobin, g/dL 8 12–15

Platelet count, ×10 /L

9
50 150–450

Leukocyte count, ×10 /L 9

8 3.5–10.0
 Component Finding Reference Range

Creatinine, mg/dL 2.5 0.8–1.3

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Figure 9.Q12
What is the most appropriate next step in management?

1. a. Red blood cell transfusion

2. b. Platelet transfusion
3. c. Gamma globulin administration
4. d. Plasma exchange
13. A 72-year-old man with chronic atrial fibrillation has been receiving dabigatran 75 mg twice daily for
the past 6 months. He has not had any thrombotic or hemorrhagic complications. He has a history of
colon polyps, for which he needs to undergo a colonoscopy with possible polypectomy. Apart from an
irregular pulse, his physical examination findings are normal. Results were normal for a complete blood
cell count and tests of renal and liver function. The calculated creatinine clearance is 28 mL/min. For how
long should dabigatran use be discontinued before the colonoscopy?

1. a. No need to discontinue

2. b. 24 hours
3. c. 48 hours
4. d. 3 days
5. e. 7 days
Lymphoid Malignancies

14. At her annual physical examination, an asymptomatic 68-year-old woman has lymphocytosis
(32×109/L) with a normal hemoglobin level and platelet count. On examination, she has 1-cm
lymphadenopathy in the cervical region and no palpable liver or spleen enlargement. A peripheral blood
smear shows identically appearing mature lymphocytes with smudge cells. Flow cytometry of the
peripheral blood lymphocytes shows a monoclonal B population with dim expression of λ light chain and
CD20 that is positive for expression of CD5, CD19, and CD23. Which of the following is the best next step
in her management?

1. a. Combination chemoimmunotherapy
2. b. Chlorambucil therapy
3. c. Allogeneic peripheral blood stem cell transplant
4. d. Combination monoclonal antibody therapy
5. e. Active monitoring for disease progression and complications
15. Ten years ago, a previously healthy 20-year-old woman presented to her physician with a 2-month
history of pruritis, drenching night sweats, unintentional weight loss, and nonproductive cough. On
examination, she had 2-cm cervical lymphadenopathy. A computed tomographic scan showed a 12-cm-
diameter anterior mediastinal mass. An excisional biopsy of a cervical lymph node showed nodular
sclerosing Hodgkin lymphoma. After she was treated with ABVD (doxorubicin
[Adriamycin], bleomycin, vinblastine, and dacarbazine) combination chemotherapy followed by involved
field radiotherapy, the disease was in complete remission. Now you see her for the first time for an annual
physical examination. The disease remains in complete remission. Compared to her peers, this patient is
at increased risk of which of the following conditions?

1. a. Breast cancer
2. b. Coronary artery disease
3. c. Hypothyroidism
4. d. Skin cancer
5. e. All of the above
16. An 80-year-old man is admitted to the hospital after falling on an icy sidewalk and fracturing his hip.
He undergoes open reduction and internal fixation of the fracture. At surgery, there does not appear to be
any bone disease at the fracture site. The patient was previously asymptomatic. Physical examination
findings are otherwise unremarkable. Serum protein electrophoresis and immunofixation show an IgM κ
monoclonal protein (0.3 g/dL). The complete blood cell count and serum creatinine levels are normal.
Skeletal survey shows no additional bone defects. Which of the following statements is true for this
patient?

1. a. He has multiple myeloma and requires treatment.

2. b. He has a lower risk of a clinically significant lymphocytic or plasma cell malignancy than
patients with an IgG monoclonal protein.
3. c. He requires a radioisotope bone scan to evaluate his bone integrity.
4. d. He requires regular follow-up and serial measurements of his monoclonal protein level.
5. e. He has a 10% annual risk of multiple myeloma.
17. A 75-year-old African American man was seen last week by his primary care physician for mild
dyspnea. He has also noted intermittent peripheral edema. During the evaluation, an electrocardiogram
showed low-voltage QRS complexes in the limb leads. The troponin T level was elevated (0.07 ng/mL).
This finding suggested the need for a coronary angiogram, which showed no significant coronary artery
disease. An echocardiogram showed diffuse left ventricular thickening with a granular texture to the
myocardium and a septal thickness of 2.5 cm (normal <1.1 cm). The complete blood cell count results
were normal. Serum and urine protein electrophoresis and immunofixation were unremarkable. Serum
free light chain levels were not increased. What is the most likely diagnosis?

1. a. AA amyloidosis
2. b. Light chain–related amyloidosis
3. c. Hypertrophic obstructive cardiomyopathy
4. d. Amyloidosis due to transthyretin deposition
5. e. Amyloidosis due to β 2-microglobulin deposition
18. A 55-year-old man presented to his primary care physician for evaluation of fatigue. He was
previously healthy with the exception of chronic musculoskeletal low back pain, for which he occasionally
takes nonsteroidal anti-inflammatory drugs. On examination, he is pale. Complete blood cell count results
are as follows: hemoglobin 8.3 g/dL, mean corpuscular volume 73 fL, leukocyte count 6.9×10 9/L, and
platelet count 398×109/L. Results of the fecal occult blood test are positive. During upper and lower
endoscopy, a 1.2×2.5-cm ulcerative lesion is noted in the lesser curvature of the stomach. The lesion is
biopsied and identified as a MALT lymphoma. Which of the following is characteristic of MALT
lymphoma?

1. a. Most cases are treated with anthracycline-based chemotherapy.

2. b. It is caused by chronic stimulation with Chlamydophila psittaci.
3. c. Radiotherapy is necessary in most cases.
4. d. It frequently undergoes transformation to a large-cell lymphoma.
 5. e. The combination of amoxicillin, omeprazole, and clarithromycin is the most appropriate first-
line treatment.
19. A 73-year-old woman presented to the emergency department with new-onset back pain, confusion,
and constipation over the past week. Her past medical history is significant only for hypertension. On
examination, she is slightly pale with slow cognition and point tenderness over the lumbar spine. Plain
films of the lumbar spine show osteolytic lesions in L2, L3, and L5. Laboratory values are as follows:
hemoglobin 9.3 g/dL, leukocyte count 4.6×109/L with a normal differential count, platelet count 230×10 9/L,
creatinine 1.6 mg/dL, total calcium 13.1 mg/dL, albumin 3.6 g/dL, and total protein 9.1 g/dL. What is the
most likely diagnosis?

1. a. Metastatic breast cancer

2. b. Hydrochlorothiazide use
3. c. Multiple myeloma
4. d. Primary hyperparathyroidism
5. e. Milk alkali syndrome
20. A 48-year-old man presents to the emergency department with a 6-week history of progressively
worsening abdominal pain and night sweats. Physical examination findings were significant for palpable
bilateral 2-cm axillary lymph nodes and diffuse abdominal tenderness with no rebound or guarding.
Computed tomography of the abdomen and pelvis showed retroperitoneal and mesenteric
lymphadenopathy. Excisional biopsy of an axillary node was positive for diffuse, large B-cell lymphoma.
Positron emission tomography showed fluorodeoxyglucose-avidity in the axillary, mesenteric, and
retroperitoneal lymph nodes. Results of the bone marrow examination were normal. Which of the
following is the best next step?

1. a. Combination therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and

prednisone (R-CHOP)
2. b. Observation
3. c. Combination therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone
(CHOP)
4. d. Autologous stem cell transplant
5. e. Involved field radiotherapy
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Answers
1. Answer d.

MDS most commonly manifests as isolated macrocytic anemia. MDS can evolve to include pancytopenia
over several years; the typical peripheral smear findings include a dimorphic erythrocyte population
(microcytes and oval macrocytes) with an overall prominent macrocytosis and an MCV around 110 fL.
The chronicity of MDS—in particular, anemia preceding the diagnosis of pancytopenia by several years—
is in contrast to the typically acute manifestation of AML, which is therefore an unlikely possibility in this
patient. Primary myelofibrosis, a myeloproliferative neoplasm, causes fibrosis in the bone marrow,
resulting in extramedullary hematopoiesis and significant splenomegaly, and typically does not cause a
macrocytic anemia. Vitamin B12 deficiency can cause a megaloblastic anemia and manifest with slowly
evolving macrocytic anemia and eventually pancytopenia, but the peripheral smear would not show a
dimorphic erythrocyte population. (See Tefferi and Vardiman in the “Suggested Reading” list.)

2. Answer a.

Extreme thrombocytosis may be reactive and occur with severe iron deficiency or inflammatory states
(with elevated erythrocyte sedimentation rates) or after splenectomy; patients are typically asymptomatic.
Clonal thrombocytosis is related to a myeloproliferative neoplasm, which usually causes splenomegaly.
Typical bone marrow findings include a hypercellular bone marrow with increased atypical
megakaryocytes in clusters. Essential thrombocythemia may cause extreme thrombocytosis (platelet
count >1,000×109/L); however, it can also occur less commonly with polycythemia rubra vera (typically
with erythrocytosis), the cellular phase of PMF, or rarely CML. The normal karyotype makes CML much
less likely since it typically manifests with the Philadelphia chromosome t(9;22). Increased reticulin
fibrosis would have been seen on the bone marrow biopsy if the patient had PMF. (See Tefferi in the
“Suggested Reading” list.)

3. Answer b.

When a patient presents with premature gallstones, one should consider whether they may be due to
pigment gallstones from chronic hemolysis causing indirect hyperbilirubinemia. The presence of
microspherocytes is consistent with hereditary spherocytosis, and the diagnostic test is an osmotic
fragility test, which identifies a congenital membrane defect. Typically, acquired warm autoimmune
hemolytic anemia, which produces positive Coombs test results, can cause spherocytes as well; however,
the history of lifelong anemia makes this diagnosis unlikely. A hemoglobin electrophoresis would help in
diagnosing thalassemia or a hemoglobinopathy; however, these conditions do not manifest with
microspherocytes on the peripheral blood film. There is no indication for a bone marrow biopsy since the
reticulocyte response is appropriate and no other cytopenias are apparent. (See Gallagher in the
“Suggested Reading” list.)

4. Answer b.

The patient has acute chest syndrome, a sickle cell anemia complication that is an indication for urgent
red cell (not plasma) exchange transfusion to decrease the hemoglobin S level to less than 30% to 35%.
Gentle fluid resuscitation is appropriate (along with oxygen support and antibiotics, since about one-third
of acute chest syndrome events are initiated by or associated with bacterial pneumonia). Aggressive fluid
resuscitation, leading to overhydration, might cause pulmonary edema and worsen the oxygenation.
Pulmonary embolism is possible, but full anticoagulation is not warranted until embolism is documented.
Use of hydroxyurea might have prevented this crisis, but it is of no value for the acute condition. (See Vij
and Machado in the “Suggested Reading” list.)

5. Answer a.

Polycythemia may be secondary, as with erythropoietin- mediated causes such as chronic hypoxemia,
living at high altitude, and high oxygen affinity hemoglobinopathies. Polycythemia vera is a
myeloproliferative neoplasm that can manifest with arterial thrombosis secondary to hyperviscosity from
the increased concentration of erythrocytes. The low erythropoietin rules out erythropoietin-mediated
causes, leaving the presumptive diagnosis of polycythemia vera. With JAK2 V617F mutation testing of
peripheral blood, results are positive for approximately 90% of patients who have polycythemia vera.
FISH for BCR-ABL testing would screen for chronic myeloid leukemia, which does not manifest with
polycythemia. Although bone marrow aspiration and biopsy would be helpful, it is not immediately
necessary and could be considered later. (See Patnaik and Tefferi in the “Suggested Reading” list.)

6. Answer c.

Hematologic complications of SLE include anemia of chronic disease, pure red cell aplasia, and warm
autoimmune hemolytic anemia (WAIHA). The presentation and laboratory data suggest hemolysis, and
the blood smear shows spherocytes. These findings are consistent with WAIHA, which causes
extravascular hemolysis. The reticulocytosis suggests that the bone marrow response is adequate. In
intravascular hemolysis, the urine is positive for hemoglobin. (See Packman in the “Suggested Reading”
list.)

7. Answer d.

Rheumatoid arthritis is a chronic inflammatory disorder that may lead to anemia of chronic disease.
Anemia of chronic disease results from the effect of elevated cytokines on hematopoiesis, including
upregulation of hepcidin, leading to increased ferritin from iron malutilization and downregulation of
ferroportin, the main iron exporting system. Transferrin is also downregulated, leading to decreased TIBC
and normal to decreased serum iron levels. (See Weiss and Goodnough in the “Suggested Reading” list.)

8. Answer c.

The timing and degree of thrombocytopenia are consistent with immune-mediated heparin-induced
thrombocytopenia type II. Unfractioned heparin and low-molecular-weight heparin are contraindicated.
Aspirin would not be the sole management agent for established thrombosis. The most appropriate step
is to start a direct thrombin inhibitor.

9. Answer d.

Presentation with a vascular thrombosis and persistence of a LAC for 12 weeks or more satisfies the
criteria for an antiphospholipid syndrome. This patient has a high risk for recurrent venous thrombosis on
discontinuing anticoagulation; thus, long-term warfarin is recommended with periodic reassessment for
safety.

10. Answer a.

DNA-based testing is reliable for patients receiving heparin or warfarin and for patients who have acute
thrombosis. However, acute thrombosis and heparin can cause lower antithrombin activity results, which
should be verified at another time, when heparin and acute thrombosis are not factors. A single positive
test result for LAC does not confirm antiphospholipid syndrome; follow-up testing at 12-week intervals is
required to demonstrate persistence of LAC. Acute thrombosis and estrogen use can lower protein S
levels; thus, abnormally low results require follow-up confirmation.

11. Answer c.

Among patients randomly assigned to receive dabigatran, overall outcomes were noninferior when
compared with the well-managed use of warfarin, thus providing no significant advantages. The group of
patients that derived the most benefit from dabigatran was the group with INRs outside the recommended
therapeutic range. Dabigatran is FDA approved only to reduce the risk of stroke and systemic embolism
in patients with nonvalvular atrial fibrillation.

12. Answer d.

Plasma exchange is the treatment of choice for thrombotic thrombocytopenic purpura (TTP). Although red
blood cell transfusion may be indicated, it does not address the underlying pathogenesis of TTP. Platelets
are thought to be contraindicated in TTP because of the theoretical possibility of worsening the TTP.
Gamma globulin is ineffective in increasing the platelet count in TTP.

13. Answer d.

Dabigatran is cleared through the kidneys. It has a prolonged half-life in patients who have a creatinine
clearance less than 30 mL/min compared with patients who have a creatinine clearance greater than 30
mL/min.

14. Answer e.

Chronic lymphocytic leukemia (CLL) is a clonal lymphoproliferative disorder of mature lymphocytes. The
clinical diagnosis requires a B-lymphocyte count of more than 5×10 9/L. Peripheral blood smears typically
show smudge cells, which are lymphocytes that have broken during processing of the slide. The clinical
course of CLL is chronic in most patients. For those with early-stage disease, standard practice is to
withhold treatment until the disease is active or progressive. However, patients need to be monitored for
disease progression, autoimmune complications, infections, and second cancers.

15. Answer e.

Hodgkin lymphoma therapy is curative in about 80% of cases. However, there are late complications of
therapy, particularly in those treated before modern chemotherapy and radiotherapy. At 15 years, the risk
of death from other causes surpasses that of risk of death from Hodgkin lymphoma. Patients are at higher
risk of secondary malignancies, cardiovascular disease, thyroid disorders, and infertility than the general
population. Many of these conditions can be attributed to chemotherapy and radiotherapy.

16. Answer d.

This patient has monoclonal gammopathy of undetermined significance (MGUS), the most common
dysproteinemia. In MGUS, the M protein level is typically less than 3 g/dL, the bone marrow has less than
10% plasma cells, and the hemoglobin, creatinine, calcium, and bone radiographs are normal. The risk of
progression to a lymphocytic or plasma cell malignancy is about 1% per year. Patients with an IgM or IgA
monoclonal protein are at higher risk of progression than those with an IgG protein. Patients with MGUS
need to be observed.

17. Answer d.

The patient has senile cardiac amyloidosis. This syndrome is usually isolated to the heart with few
clinically significant deposits elsewhere, and the echocardiographic findings are often out of proportion to
the degree of symptoms. Transthyretin is the protein causing the amyloid deposits; most patients have
wild-type transthyretin.

18. Answer e.

With combination antibiotic therapy, 70% of gastric MALT lymphomas are cured. In cases refractory to
antibiotics, tumors may carry the t(11;18) translocation, and involved field radiotherapy is effective.
Combination chemotherapy is reserved for advanced disease. The majority of cases are associated
with Helicobacter pylori infection.

19. Answer c.

This patient has multiple myeloma with evidence of end-organ damage from the plasma cell proliferative
disorder (hypercalcemia, renal failure, anemia, and osteolytic bone lesions). The other answer choices
are possible causes of hypercalcemia, but only multiple myeloma accounts for all the presenting
symptoms, including the elevated level of total protein.

20. Answer a.

This patient has advanced-stage, diffuse, large B-cell lymphoma, and R-CHOP chemotherapy is the
standard of care. Rituximab is an anti-CD20 monoclonal antibody that improves overall survival when
added to CHOP chemotherapy for aggressive B-cell lymphomas. For patients whose disease relapses or
is refractory, autologous stem cell transplant is the standard therapy. Radiotherapy can be used in
combination with chemotherapy in early-stage (I-IIA) nonbulky disease but is not standard therapy for
advanced disease.

Suggested Reading
Gallagher PG. Red cell membrane disorders. Hematology Am Soc Hematol Educ Program. 2005:13–
8.Find this resource:
Packman CH. Hemolytic anemia due to warm autoantibodies. Blood Rev. 2008 Jan;22(1):17–31. Epub
2007 Sep 27.Find this resource:
Patnaik MM, Tefferi A. The complete evaluation of erythrocytosis: congenital and acquired. Leukemia.
2009 May;23(5):834–44. Epub 2009 Mar 19.Find this resource:
Tefferi A. Annual clinical updates in hematological malignancies: a continuing medical education series:
polycythemia vera and essential thrombocythemia: 2011 update on diagnosis, risk-stratification, and
management. Am J Hematol. 2011 Mar;86(3):292–301.Find this resource:
Tefferi A, Vardiman JW. Myelodysplastic syndromes. N Engl J Med. 2009 Nov 5;361(19):1872–85.Find
this resource:
Vij R, Machado RF. Pulmonary complications of hemoglobinopathies. Chest. 2010 Oct;138(4):973–
83.Find this resource:
Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005 Mar 10;352(10):1011–23.Find
this resource: