Hematology and Oncology Practice Questions — USMLE Step 2 CK

Question 1Question →

A 72-year-old woman is brought to the emergency department by her family after sustaining a fall at home. Four weeks ago, she was evaluated at an urgent care clinic for progressive fatigue, a smooth, red tongue, and mild tingling in her feet. At that time, her hemoglobin was 9.2 g/dL, mean corpuscular volume was 115 fL, and a peripheral blood smear showed hypersegmented neutrophils. She was diagnosed with megaloblastic anemia and started on high-dose oral folic acid supplementation by the urgent care provider.

Today, her family reports that her fatigue has improved, but her unsteadiness and numbness have significantly worsened over the past two weeks, leading to her fall. She has a past medical history of Hashimoto thyroiditis and takes levothyroxine. She consumes a standard omnivorous diet.

Vital signs are within normal limits. Neurologic examination reveals decreased vibratory sensation and proprioception in the bilateral lower extremities. Her gait is markedly wide-based and ataxic. Romberg test is positive. Repeat laboratory studies today show a hemoglobin of 10.8 g/dL and a mean corpuscular volume of 102 fL.

Which of the following best explains the clinical course of this patient?

Rapid hematopoiesis induced by folic acid led to a severe intracellular potassium shift and resultant hypokalemia.

High-dose folic acid caused direct toxic demyelination of the posterior columns and lateral corticospinal tracts.

Folic acid supplementation corrected the hematologic deficit but allowed the underlying neurologic degeneration to progress.

The increase in red blood cell mass precipitated an acute cardiopulmonary exacerbation due to increased blood viscosity.

Resolution of macrocytosis unmasked a coexisting iron deficiency, leading to severe cerebral hypoxia.

Show answer & explanation

Answer: Folic acid supplementation corrected the hematologic deficit but allowed the underlying neurologic degeneration to progress.

Answer

The patient's clinical course is best explained by folic acid supplementation correcting the megaloblastic anemia while allowing the underlying vitamin B12 deficiency-mediated neurologic degeneration to progress.

The correct answer explains that folic acid supplementation corrects the hematologic manifestations of vitamin B12 deficiency without treating the neurologic manifestations. Vitamin B12 and folate are both required for DNA synthesis (via the conversion of homocysteine to methionine). Providing high doses of folate can bypass the B12-dependent step in this pathway, resolving the megaloblastic anemia. However, vitamin B12 is uniquely required for the conversion of methylmalonyl-CoA to succinyl-CoA, which is necessary for proper myelin synthesis. Because folate does not participate in this pathway, the demyelination of the dorsal columns and lateral corticospinal tracts (subacute combined degeneration) continues unchecked, leading to worsening sensory ataxia, loss of proprioception, and falls.

Step-by-Step Solution

1

Identify the patient's initial underlying diagnosis based on her clinical presentation and laboratory findings.

The patient initially presented with a macrocytic anemia, hypersegmented neutrophils, a smooth red tongue (glossitis), and mild neurologic symptoms (tingling). Given her history of Hashimoto thyroiditis, she most likely has pernicious anemia leading to vitamin B12 deficiency.

Establishing the true underlying diagnosis is necessary because the urgent care provider only diagnosed a generic 'megaloblastic anemia' and initiated incomplete therapy.

2

Analyze the physiological effect of the prescribed treatment (folic acid) on the patient's underlying condition.

The patient was treated with isolated folic acid. Her anemia improved (hemoglobin increased from 9.2 to 10.8 g/dL), but her neurologic symptoms significantly worsened, progressing to severe ataxia and loss of proprioception.

To connect the specific medical intervention with the divergent changes in her hematologic and neurologic status.

3

Determine the biochemical mechanism that explains this divergent clinical response.

Folate administration bypasses the metabolic block in DNA synthesis caused by B12 deficiency, successfully correcting the hematologic abnormalities. However, folate cannot replace vitamin B12 in the conversion of methylmalonyl-CoA to succinyl-CoA, a step that is crucial for myelin synthesis. Therefore, the subacute combined degeneration of the spinal cord progresses unchecked.

To explain the core pathophysiological concept of why folic acid masks vitamin B12 deficiency.

Key Concept

In a patient with vitamin B12 deficiency, inappropriate monotherapy with folic acid can correct the megaloblastic anemia but will mask and fail to halt the progression of subacute combined degeneration of the spinal cord.

Question 2Question →

While undergoing induction chemotherapy for acute myeloid leukemia, a $54$ -year-old male patient receives a transfusion of packed red blood cells due to a hemoglobin level of $6.8 \text{ g/dL}$ . Approximately twenty minutes after the infusion begins, the patient acutely develops rigors, severe lower back pain, and a feeling of impending doom. Vital signs reveal a temperature of $39.4^\circ\text{C}$ ( $102.9^\circ\text{F}$ ), blood pressure of $88/54 \text{ mmHg}$ , heart rate of $122/\text{min}$ , and respiratory rate of $24/\text{min}$ . Urine collected from his catheter is noted to be dark and reddish-brown. Which of the following is the most appropriate initial step in the management of this patient?

Stop the transfusion and rapidly infuse intravenous normal saline

Discontinue the transfusion and administer broad-spectrum intravenous antibiotics

Interrupt the transfusion and transport the patient for an urgent computed tomography scan of the abdomen

Continue the transfusion while administering intravenous diphenhydramine and oral acetaminophen

Terminate the transfusion and formally reprimand the medical staff for an administration error

Show answer & explanation

Answer: Stop the transfusion and rapidly infuse intravenous normal saline

Answer

The most appropriate initial step is to stop the transfusion and rapidly infuse intravenous normal saline.

The patient's presentation of fever, rigors, flank pain, dark urine (hemoglobinuria), and hypotension occurring within minutes of starting a red blood cell transfusion is the classic presentation of an acute hemolytic transfusion reaction (AHTR). This is typically caused by preformed host antibodies attacking donor red blood cells (e.g., ABO incompatibility), leading to massive intravascular hemolysis. The destroyed red blood cells release hemoglobin, which can precipitate in the renal tubules and cause acute kidney injury. The most critical first step is to immediately stop the transfusion. This must be followed closely by aggressive intravenous fluid resuscitation with normal saline to support blood pressure, maintain renal perfusion, and promote diuresis to prevent acute tubular necrosis.

Step-by-Step Solution

1

Analyze the patient's acute symptoms and vital signs.

The patient developed fever, rigors, flank pain, hypotension, and dark urine shortly after starting a blood transfusion.

Identifying the temporal relationship between the transfusion and the onset of systemic symptoms is crucial for diagnosis.

2

Establish the most likely diagnosis.

The presentation is classic for an acute hemolytic transfusion reaction (AHTR), likely due to ABO incompatibility.

The triad of fever, flank pain, and red-brown urine (hemoglobinuria) during a transfusion strongly indicates intravascular hemolysis.

3

Determine the most appropriate initial management.

The immediate priority is to stop the transfusion and administer aggressive intravenous fluids.

Stopping the transfusion prevents further reaction, while vigorous hydration maintains blood pressure and protects the kidneys from acute tubular necrosis caused by free hemoglobin.

Key Concept

The classic presentation of an acute hemolytic transfusion reaction includes fever, flank pain, hemoglobinuria, and hypotension. The most critical first step in management is stopping the transfusion immediately and administering aggressive intravenous hydration.

Estimated Time:1m 0s

Question 3Question →

For each of the following patient vignettes presenting with complex hematologic and oncologic abnormalities, match the clinical scenario to the most appropriate definitive diagnostic test or initial next step in management.

Click a left item, then click its matching right item

Show answer & explanation

Answer

The clinical presentations match their respective diagnostic and management steps as follows: The patient with hepatic vein thrombosis and dark urine matches with flow cytometry for missing anchored proteins (PNH). The patient with cold-induced acrocyanosis and hemolysis matches with direct antiglobulin testing for C3 (Cold Agglutinin Disease). The patient with an IgM spike and retinal engorgement matches with urgent therapeutic plasma exchange (Waldenström Macroglobulinemia with hyperviscosity). The patient with profound post-hepatitis pancytopenia matches with bone marrow biopsy (Aplastic Anemia).

Each patient's unique constellation of symptoms precisely targets a distinct pathophysiologic process in hematology/oncology. PNH is marked by complement-mediated hemolysis due to absent GPI-anchored proteins (requiring flow cytometry). Cold Agglutinin Disease is driven by IgM-mediated complement fixation in cold extremities (requiring DAT for C3). Waldenström Macroglobulinemia causes hyperviscosity through excessive IgM (requiring emergent plasma exchange). Hepatitis-associated aplastic anemia results in T-cell mediated destruction of stem cells (requiring bone marrow biopsy).

Step-by-Step Solution

1

Analyze the 35-year-old man's vignette.

Identify the triad of Budd-Chiari syndrome, hemolysis, and morning hemoglobinuria.

These findings are highly indicative of Paroxysmal Nocturnal Hemoglobinuria, which requires flow cytometry to detect the absence of CD55/CD59.

2

Analyze the 65-year-old woman's vignette.

Identify acrocyanosis and anemia that worsen in winter.

These cold-precipitated symptoms point to Cold Agglutinin Disease, confirmed by a direct antiglobulin test demonstrating bound C3 without IgG.

3

Analyze the 72-year-old man's vignette.

Identify epistaxis, retinal vein engorgement, neuropathy, and an IgM spike.

These are classic signs of hyperviscosity syndrome secondary to Waldenström Macroglobulinemia. This is an emergency necessitating urgent therapeutic plasma exchange.

4

Analyze the 28-year-old woman's vignette.

Identify severe pancytopenia with an inappropriately low reticulocyte count following an episode of viral hepatitis.

This presentation strongly suggests acquired aplastic anemia, which must be definitively diagnosed via bone marrow aspiration and biopsy.

Key Concept

Identifying complex hematologic disorders (PNH, CAD, Aplastic Anemia) and oncologic emergencies (Hyperviscosity Syndrome) to determine the exact next step in diagnostic confirmation or emergent treatment.

Estimated Time:2m 30s

Question 4Question →

A $38$ -year-old woman is brought to the emergency department by her husband due to sudden-onset confusion, agitation, and strange behavior that began this morning. For the past $3$ days, she has complained of profound fatigue, generalized weakness, and subjective fevers. She has no significant past medical history and takes no medications. Her temperature is $38.2^\circ\text{C}$ ( $100.8^\circ\text{F}$ ), pulse is $112\text{/min}$ , blood pressure is $142/88\text{ mmHg}$ , and respiratory rate is $18\text{/min}$ . Physical examination reveals a confused and agitated woman. There are numerous non-blanching, pinpoint erythematous macules on her bilateral lower extremities. Neurological examination reveals no focal motor or sensory deficits, but she is oriented only to person.

Laboratory studies reveal:
Hemoglobin: $7.4\text{ g/dL}$
Platelet count: $22,000/\mu\text{L}$
Leukocyte count: $9,200/\mu\text{L}$
Creatinine: $2.2\text{ mg/dL}$
Total bilirubin: $3.8\text{ mg/dL}$
Indirect bilirubin: $3.1\text{ mg/dL}$
Thyroid-stimulating hormone (TSH): $4.8\text{ }\mu\text{U/mL}$ (Normal: $0.4-4.0\text{ }\mu\text{U/mL}$ )

A peripheral blood smear demonstrates numerous fragmented red blood cells.

Which of the following is the most appropriate next step in the management of this patient?

Transfuse pooled donor platelets

Administer intravenous ceftriaxone and vancomycin

Initiate therapeutic plasma exchange

Administer intravenous haloperidol and arrange psychiatric admission

Defer interventions until informed consent is obtained from the patient's parents

Show answer & explanation

Answer: Initiate therapeutic plasma exchange

Answer

The correct answer is to initiate therapeutic plasma exchange.

The correct answer is to initiate therapeutic plasma exchange. This patient presents with the classic pentad of Thrombotic Thrombocytopenic Purpura (TTP): fever, microangiopathic hemolytic anemia (schistocytes, elevated indirect bilirubin, anemia), thrombocytopenia, renal insufficiency (elevated creatinine), and neurologic symptoms (confusion, agitation). TTP is a life-threatening hematologic emergency caused by severe deficiency of the von Willebrand factor (vWF)-cleaving protease ADAMTS13, leading to unchecked platelet aggregation and microvascular thrombosis. Therapeutic plasma exchange (plasmapheresis) is the definitive next step in management as it removes the offending autoantibodies and replenishes functional ADAMTS13.

Step-by-Step Solution

1

Analyze the patient's clinical presentation and vitals.

A

38

-year-old woman presents with acute-onset confusion, fever (

38.2^\circ\text{C}

), and petechiae.

To identify the primary organ systems involved (neurologic and dermatologic/hematologic) in an acutely ill patient.

2

Interpret the laboratory findings and peripheral blood smear.

Labs reveal severe thrombocytopenia (

22,000/\mu\text{L}

), anemia (

7.4\text{ g/dL}

) with elevated indirect bilirubin, acute kidney injury (creatinine

2.2\text{ mg/dL}

), and schistocytes on smear.

To confirm the presence of Microangiopathic Hemolytic Anemia (MAHA) and differentiate it from other causes of thrombocytopenia.

3

Synthesize findings to establish the most likely diagnosis.

The combination of MAHA, thrombocytopenia, fever, renal dysfunction, and neurologic abnormalities represents the classic pentad of Thrombotic Thrombocytopenic Purpura (TTP).

To select the appropriate life-saving intervention, as TTP requires immediate, specialized treatment.

4

Determine the best next step in management based on the diagnosis of TTP.

Therapeutic plasma exchange must be initiated immediately.

Plasma exchange removes autoantibodies against ADAMTS13 and provides the functional enzyme, reversing the microvascular thrombosis.

Key Concept

Diagnosis and emergent management of Thrombotic Thrombocytopenic Purpura (TTP) with therapeutic plasma exchange.

Estimated Time:1m 30s

Question 5Question →

A 22-year-old man presents to the emergency department complaining of severe chest pain and difficulty breathing for the past 48 hours. He has a known history of homozygous sickle cell disease (HbSS). Vital signs show a temperature of 39.1°C (102.4°F), blood pressure of 92/58 mm Hg, heart rate of 128/min, and respiratory rate of 34/min. Pulse oximetry is 83% while receiving high-flow oxygen via a non-rebreather mask. Physical examination reveals severe respiratory distress, scleral icterus, and bilateral dullness to percussion with widespread crackles. A portable chest radiograph displays new diffuse, multilobar alveolar infiltrates.

Laboratory analysis reveals the following:

Laboratory Test	Result
Hemoglobin	6.9 g/dL (baseline 8.5 g/dL)
Leukocytes	24,000/mm³
Platelets	380,000/mm³
Reticulocytes	15%

The patient has been started on intravenous fluids, broad-spectrum antibiotics (ceftriaxone and azithromycin), and adequate pain management. Which of the following is the most appropriate next step in management?

Administer intravenous furosemide

CT angiography of the chest

Exchange blood transfusion

Simple red blood cell transfusion

Switch to intravenous piperacillin-tazobactam

Show answer & explanation

Answer: Exchange blood transfusion

Answer

Exchange blood transfusion is the most appropriate next step in management for this patient with severe acute chest syndrome.

The correct answer is exchange blood transfusion. This patient is presenting with acute chest syndrome (ACS), a life-threatening complication of sickle cell disease characterized by fever, chest pain, new pulmonary infiltrates, and hypoxemia. His presentation is severe, evidenced by multilobar infiltrates and profound hypoxemia (83% on a non-rebreather mask). The management of severe ACS requires an exchange blood transfusion. This procedure removes the patient's sickled red blood cells (HbS) and replaces them with normal red blood cells (HbA), rapidly improving oxygenation and halting the vaso-occlusive cycle without significantly raising overall blood viscosity. Simple transfusion is typically reserved for mild cases where the hemoglobin has dropped significantly but hypoxemia is less severe.

Step-by-Step Solution

1

Identify the primary diagnosis based on the clinical presentation.

The patient with sickle cell disease presents with fever, chest pain, new pulmonary infiltrates, and severe hypoxemia, establishing the diagnosis of Acute Chest Syndrome (ACS).

Recognizing ACS is critical as it is a major cause of mortality in sickle cell patients and requires specific, rapid intervention.

2

Determine the severity of the acute chest syndrome.

The presence of multilobar infiltrates, severe hypoxemia (SpO2 83% on high-flow oxygen), and hemodynamic instability indicates severe ACS.

Severity classification dictates the choice between a simple red blood cell transfusion and an exchange transfusion.

3

Select the appropriate targeted intervention for severe ACS.

Exchange blood transfusion is indicated rather than a simple transfusion.

Exchange transfusion rapidly decreases the percentage of hemoglobin S and improves oxygen-carrying capacity without significantly increasing overall blood viscosity, avoiding the exacerbation of vaso-occlusion.

Key Concept

Severe acute chest syndrome in sickle cell disease requires exchange blood transfusion to rapidly reduce hemoglobin S levels and improve oxygenation without causing hyperviscosity.

Question 6Question →

A 54-year-old woman with a history of hormone receptor-positive metastatic breast cancer presents to the emergency department with a 2-day history of progressively worsening mid-back pain. Over the past 12 hours, she has developed difficulty walking due to bilateral leg weakness and reports a new onset of urinary incontinence. Physical examination reveals 3/5 muscle strength in the lower extremities bilaterally, exaggerated patellar and Achilles deep tendon reflexes, and decreased sensation to pinprick below the level of the nipples. Vital signs are within normal limits. Arrange the following steps in the most appropriate sequential order for the immediate evaluation and management of this patient's current condition.

Drag items to arrange them in the correct order

Show answer & explanation

Answer

The correct sequence is: Administration of high-dose intravenous dexamethasone, followed by Magnetic resonance imaging (MRI) of the entire spine, then Consultation with neurosurgery or radiation oncology, and finally Initiation of targeted decompressive therapy.

Malignant spinal cord compression is an oncologic emergency. The immediate priority is preserving neurologic function by reducing vasogenic edema with high-dose intravenous corticosteroids (e.g., dexamethasone). This must be done empirically as soon as the condition is suspected, even before diagnostic imaging. After steroids are given, an MRI of the entire spine is obtained to confirm the diagnosis and assess the extent of the disease. Following imaging, surgical and/or radiation oncology consultation is obtained to plan and initiate definitive decompressive therapy.

Step-by-Step Solution

1

Administer high-dose intravenous dexamethasone.

Decreases peritumoral vasogenic edema and relieves pressure on the spinal cord.

Neurologic deficits in malignant spinal cord compression can become irreversible quickly. Steroids are the most critical initial step and must be given before waiting for imaging.

2

Perform an MRI of the entire spine.

Visualizes the epidural metastasis and determines the level of compression.

MRI is the imaging modality of choice to confirm the diagnosis and delineate the extent of the disease.

3

Consult specialized services (neurosurgery or radiation oncology).

Establishes a definitive treatment plan based on imaging findings.

Expert evaluation is necessary to weigh the benefits of surgery versus radiation based on spinal stability, tumor radiosensitivity, and overall prognosis.

4

Initiate definitive decompressive therapy.

Provides long-term relief of cord compression and local tumor control.

This is the final intervention in the acute management pathway to prevent permanent paralysis.

Key Concept

In patients with suspected malignant spinal cord compression presenting with neurologic deficits, intravenous corticosteroids must be administered immediately prior to diagnostic imaging to prevent irreversible neurologic damage.

Estimated Time:1m 30s

Question 7Question →

A $19$ -year-old male of Mediterranean descent is admitted to the hospital with newly diagnosed Burkitt lymphoma. He has a massive abdominal tumor burden. Baseline laboratory studies reveal a serum uric acid level of $14.2 \text{ mg/dL}$ and a serum creatinine of $1.9 \text{ mg/dL}$ . To mitigate the risk of tumor lysis syndrome, he receives aggressive intravenous hydration and a dose of rasburicase. Forty-eight hours later, the patient acutely develops shortness of breath, fatigue, and bluish discoloration of his lips and fingertips. Vital signs are: temperature $37.1^\circ \text{C}$ , heart rate $128$ /min, blood pressure $105/65$ mmHg, and respiratory rate $28$ /min. Pulse oximetry shows an oxygen saturation of $84\%$ on room air, which does not improve following the administration of $100\%$ oxygen via a non-rebreather mask. Arterial blood gas on $100\%$ oxygen shows a PaO $_2$ of $410$ mmHg. Blood drawn from the patient's vein appears chocolate-brown. Laboratory studies show a rapid decline in hemoglobin from $14.5 \text{ g/dL}$ to $8.2 \text{ g/dL}$ . A peripheral blood smear reveals numerous bite cells and Heinz bodies. Which of the following is the most appropriate next step in the management of this patient's acute respiratory compromise?

Perform red blood cell exchange transfusion

Administer intravenous methylene blue

Administer intravenous ascorbic acid

Initiate therapeutic enoxaparin and order a CT pulmonary angiography

Transfuse two units of packed red blood cells

Show answer & explanation

Answer: Perform red blood cell exchange transfusion

Answer

Perform red blood cell exchange transfusion

The correct answer is to perform a red blood cell exchange transfusion. This patient has developed acute severe methemoglobinemia and hemolytic anemia secondary to rasburicase administration. Rasburicase is a recombinant urate oxidase used to prevent tumor lysis syndrome by converting uric acid to allantoin. This reaction generates large amounts of hydrogen peroxide (

H_2O_2

) as a byproduct. In patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency (suggested by his Mediterranean descent and the presence of bite cells and Heinz bodies on the blood smear), the inability to generate NADPH renders erythrocytes highly susceptible to oxidative stress. This stress simultaneously causes hemolysis and oxidizes normal ferrous hemoglobin (Fe

^{2+}

) to ferric methemoglobin (Fe

^{3+}

). Methemoglobinemia is characterized by central cyanosis, a 'saturation gap' (low pulse oximetry reading despite a high PaO

_2

on arterial blood gas), and chocolate-brown blood. While methylene blue is the standard first-line treatment for methemoglobinemia, its mechanism of action requires NADPH from the G6PD pathway. In G6PD-deficient patients, methylene blue is not only ineffective but also acts as a potent exogenous oxidant, precipitating a potentially fatal hemolytic crisis. Therefore, severe symptomatic methemoglobinemia in a G6PD-deficient patient must be managed with a red blood cell exchange transfusion (or hyperbaric oxygen therapy) to physically remove the methemoglobin and replace it with functional red blood cells.

Step-by-Step Solution

1

Analyze the patient's history and peripheral blood smear.

The presence of bite cells, Heinz bodies, and Mediterranean descent in the context of an oxidative trigger confirms underlying glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Identifying this underlying enzyme deficiency is critical, as it fundamentally alters the safety profile of subsequent therapeutic interventions.

2

Interpret the oxygenation paradox and distinct clinical signs.

A persistently low pulse oximetry reading despite a very high PaO2 (a 'saturation gap'), accompanied by central cyanosis and chocolate-brown blood, confirms the diagnosis of severe methemoglobinemia.

Rasburicase (a recombinant urate oxidase) catalyzed the breakdown of uric acid into allantoin and hydrogen peroxide. The accumulated hydrogen peroxide caused massive oxidative stress, leading to both hemolysis and the oxidation of hemoglobin to methemoglobin.

3

Select the appropriate therapy for methemoglobinemia based on the patient's G6PD status.

Red blood cell exchange transfusion is chosen as the definitive intervention.

The standard first-line treatment, methylene blue, requires the G6PD-dependent production of NADPH to reduce methemoglobin. In G6PD deficiency, methylene blue is ineffective and acts as a dangerous oxidant, while exchange transfusion safely removes the defective erythrocytes.

Key Concept

Patients with G6PD deficiency who develop severe, symptomatic methemoglobinemia (e.g., secondary to rasburicase-induced oxidative stress) must be treated with exchange transfusion or hyperbaric oxygen, as methylene blue is strictly contraindicated.

Question 8Question →

A 24-year-old primigravid woman at 26 weeks gestation is evaluated during a routine prenatal visit. She has no fatigue, dyspnea, or palpitations. Her pregnancy has been uncomplicated. She takes a daily prenatal multivitamin. Blood pressure is 112/70 mm Hg and pulse is 78/min. Physical examination shows a gravid uterus consistent with gestational age and no peripheral edema.

Laboratory results are as follows:

Test	Result
Hemoglobin	10.9 g/dL
Hematocrit	32%
Mean corpuscular volume	88 fL
White blood cell count	8,500/mm³
Platelet count	240,000/mm³
Serum ferritin	55 ng/mL

Which of the following is the most appropriate next step in the management of this patient's hematologic findings?

Reassurance and routine prenatal care

Initiation of high-dose oral ferrous sulfate

Measurement of serum methylmalonic acid

Peripheral blood smear evaluation

Hemoglobin electrophoresis

Show answer & explanation

Answer: Reassurance and routine prenatal care

Answer

Reassurance and routine prenatal care

The correct answer is reassurance and routine prenatal care because this patient's hematologic findings represent the normal physiologic changes of pregnancy. During pregnancy, plasma volume expands by approximately 40-50%, while red blood cell mass increases by only 20-30%. This disproportionate increase leads to a hemodilution effect, lowering the hemoglobin and hematocrit concentrations. In the first and third trimesters, the lower limit of normal for hemoglobin is 11.0 g/dL, while in the second trimester, it drops to 10.5 g/dL. Since this patient is at 26 weeks gestation (second trimester) with a hemoglobin of 10.9 g/dL, normal mean corpuscular volume (MCV), and normal ferritin, she does not have true iron deficiency anemia and requires no further intervention.

Step-by-Step Solution

1

Analyze the hemoglobin level in the context of the patient's gestational age.

The hemoglobin is 10.9 g/dL at 26 weeks gestation, which is within normal limits. The threshold for anemia in the second trimester is < 10.5 g/dL.

Pregnancy induces a disproportionate increase in plasma volume relative to red blood cell mass, leading to physiologic hemodilution.

2

Evaluate the iron stores and red blood cell indices to rule out true hematologic deficiency.

The serum ferritin is 55 ng/mL (normal) and the mean corpuscular volume is 88 fL (normal).

Iron deficiency is the most common cause of true anemia in pregnancy and must be differentiated from expected physiologic changes.

3

Determine the appropriate management plan based on the findings.

No additional hematologic intervention or diagnostic workup is required.

The patient is asymptomatic and exhibits a completely normal physiologic dilutional state.

Key Concept

Physiologic dilutional anemia of pregnancy occurs due to a greater expansion of plasma volume compared to red blood cell mass, resulting in an expected hemoglobin drop (minimum > 10.5 g/dL in the second trimester) without true iron deficiency.

Question 9Question →

Review the following clinical presentations of patients who develop complications during or shortly after receiving blood product transfusions. Match each patient's clinical scenario with the primary pathophysiologic mechanism responsible for their reaction.

Click a left item, then click its matching right item

Show answer & explanation

Answer

The correct matches are: The 35-year-old with isolated fever matches cytokine accumulation (FNHTR). The 52-year-old with normal JVP and pulmonary infiltrates matches donor anti-leukocyte antibodies (TRALI). The 78-year-old with elevated JVP and S3 matches rapid volume expansion (TACO). The 24-year-old with flank pain and dark urine matches preformed recipient IgM (AHTR). The 29-year-old with immediate anaphylaxis matches recipient anti-IgA antibodies.

Each clinical vignette contains specific differentiating features that pinpoint the diagnosis. The timing (seconds vs hours), volume status (elevated vs normal JVP), and presence of end-organ damage (hemolysis, anaphylaxis) directly correlate with the five distinct pathophysiologic mechanisms of transfusion complications.

Step-by-Step Solution

1

Analyze the onset time and primary organ systems involved in each vignette.

Identifies the core syndrome: isolated fever vs. pulmonary edema vs. systemic hemolysis vs. anaphylaxis.

Transfusion reactions are heavily differentiated by the timing of onset and specific end-organ manifestations.

2

Differentiate the two pulmonary edema presentations by assessing volume status.

The patient with normal JVP has noncardiogenic edema (TRALI), while the patient with elevated JVP, hypertension, and an S3 has cardiogenic edema (TACO).

Both TRALI and TACO present with respiratory distress and bilateral infiltrates, making volume status indicators (JVP, blood pressure) the critical distinguishing factors.

3

Differentiate the acute febrile reactions by looking for signs of hemolysis.

The patient with clear urine and stable vitals has a simple febrile nonhemolytic reaction. The patient with dark urine, shock, and DIC has an acute hemolytic reaction.

Febrile nonhemolytic reactions are benign and self-limiting, whereas acute hemolytic reactions are life-threatening medical emergencies driven by complement-mediated erythrocyte destruction.

4

Map the identified clinical syndromes to their underlying immunologic or physiologic mechanisms.

Finalizes the pairings based on standard pathophysiologic pathways for FNHTR, TRALI, TACO, AHTR, and anaphylaxis.

Understanding the mechanism is essential for proper future prevention (e.g., leukoreduction for FNHTR, IgA-deficient blood products for anaphylaxis).

Key Concept

Clinical presentation and pathophysiology of major transfusion reactions

Question 10Question →

A 62-year-old woman is evaluated on postoperative day 6 following a right total knee arthroplasty. Since the surgery, she has been receiving subcutaneous unfractionated heparin for deep vein thrombosis prophylaxis. Today, she reports new-onset left calf pain and swelling.

Vital signs are within normal limits. Physical examination reveals left calf tenderness, erythema, and 2+ pitting edema up to the knee.

Laboratory studies on admission:
Hemoglobin: 13.2 g/dL
Leukocyte count: 8,500/mm³
Platelet count: 260,000/mm³

Laboratory studies today:
Hemoglobin: 12.8 g/dL
Leukocyte count: 9,200/mm³
Platelet count: 110,000/mm³

A duplex ultrasonography of the left lower extremity demonstrates a noncompressible popliteal vein. Which of the following is the most appropriate next step in management?

Discontinue unfractionated heparin and initiate argatroban

Discontinue unfractionated heparin and initiate warfarin

Switch unfractionated heparin to enoxaparin

Transfuse irradiated pooled platelets

Continue unfractionated heparin and obtain a CT pulmonary angiogram

Show answer & explanation

Answer: Discontinue unfractionated heparin and initiate argatroban

Answer

Discontinue unfractionated heparin and initiate argatroban

This patient's presentation of a >50% drop in platelets occurring 5-10 days after heparin initiation, combined with a new deep vein thrombosis, is highly suggestive of type 2 heparin-induced thrombocytopenia (HIT). HIT is an immune-mediated disorder caused by antibodies against heparin-platelet factor 4 (PF4) complexes, which activate platelets and create a profound prothrombotic state. The most critical next step is to immediately discontinue all heparin products and initiate non-heparin anticoagulation, such as a direct thrombin inhibitor (e.g., argatroban, bivalirudin) or an indirect factor Xa inhibitor (e.g., fondaparinux).

Step-by-Step Solution

1

Calculate the 4T score for Heparin-Induced Thrombocytopenia.

The patient has a platelet count drop of >50% (2 points), timing between days 5 and 10 (2 points), new thrombosis (2 points), and no other clear cause (2 points), yielding a high probability score.

To determine the pretest probability of HIT before changing therapy.

2

Determine the immediate management for high-probability HIT.

Stop the offending agent (heparin) and start a direct thrombin inhibitor (argatroban).

Continuing heparin worsens the thrombosis, and untreated HIT carries a high risk of catastrophic thrombotic events.

Key Concept

Diagnosis and management of Heparin-Induced Thrombocytopenia (HIT)

Question 11Question →

A $28$ -year-old primigravida at $32$ weeks gestation presents to the emergency department reporting acute-onset fatigue, shortness of breath, and dark urine for the past $24$ hours. $3$ days ago, she was diagnosed with an uncomplicated urinary tract infection and prescribed nitrofurantoin. Her prenatal course has otherwise been unremarkable.

Temperature is $37.4^\circ\text{C}$ ( $99.3^\circ\text{F}$ ), blood pressure is $110/70$ mmHg, pulse is $112$ /min, and respirations are $20$ /min. Physical examination reveals conjunctival pallor and mild scleral icterus. The uterine fundus is consistent with gestational age. Continuous fetal heart rate monitoring demonstrates a baseline of $165$ /min, minimal variability, and occasional variable decelerations.

Laboratory studies show:

Test	Result	Reference Range
Hemoglobin	$6.8$ g/dL	$11.0$ - $14.0$ g/dL
Platelets	$185,000/\mu\text{L}$	$150,000$ - $400,000/\mu\text{L}$
Leukocytes	$9,500/\mu\text{L}$	$4,500$ - $11,000/\mu\text{L}$
Mean corpuscular volume	$94$ fL	$80$ - $100$ fL
Lactate dehydrogenase	$840$ U/L	$100$ - $250$ U/L
Total bilirubin	$4.5$ mg/dL	$0.1$ - $1.2$ mg/dL
Direct bilirubin	$0.5$ mg/dL	$0.0$ - $0.3$ mg/dL
Aspartate aminotransferase	$25$ U/L	$10$ - $40$ U/L
Alanine aminotransferase	$22$ U/L	$7$ - $56$ U/L
Creatinine	$0.7$ mg/dL	$0.5$ - $1.1$ mg/dL

A peripheral blood smear stained with Wright-Giemsa is obtained (see image) and reveals scattered erythrocytes with irregular, semi-circular marginal defects.

Which of the following is the most appropriate next step in management?

Initiate intravenous piperacillin-tazobactam and admit to the intensive care unit

Reassure the patient and prescribe oral iron supplementation for physiologic anemia

Discontinue the current antibiotic and prepare for packed red blood cell transfusion

Proceed directly to emergent cesarean delivery for non-reassuring fetal status

Order a comprehensive thyroid panel including thyroid-stimulating hormone

Show answer & explanation

Answer: Discontinue the current antibiotic and prepare for packed red blood cell transfusion

Answer

Discontinue the current antibiotic and prepare for packed red blood cell transfusion.

The correct answer involves discontinuing the offending medication and providing a blood transfusion. The patient is experiencing acute hemolytic anemia due to Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency, triggered by the recent initiation of nitrofurantoin. This is evidenced by her acute drop in hemoglobin, elevated indirect bilirubin, elevated lactate dehydrogenase, and the classic peripheral smear finding of degmacytes (bite cells). In G6PD deficiency, oxidative stress causes hemoglobin to denature into Heinz bodies, which are subsequently 'bitten' out by splenic macrophages. The symptomatic anemia (tachycardia, dyspnea) and non-reassuring fetal status are secondary to decreased maternal oxygen carrying capacity. The most appropriate next step is to stop the offending agent and provide a blood transfusion to restore oxygen delivery, which simultaneously acts as intrauterine resuscitation for the fetus.

Step-by-Step Solution

1

Analyze the clinical presentation and laboratory data to identify the primary pathophysiologic process.

The patient has acute severe normocytic anemia, elevated lactate dehydrogenase, indirect hyperbilirubinemia, and hemoglobinuria (dark urine), indicating an acute hemolytic crisis.

Recognizing the presence of active hemolysis is the critical first step before determining the specific etiology.

2

Correlate the hemolytic crisis with the patient's recent medical history and peripheral smear findings.

The recent initiation of nitrofurantoin combined with the presence of degmacytes (bite cells) on the peripheral smear confirms oxidative stress-induced hemolysis, which is characteristic of Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency.

Identifying the specific trigger is necessary to halt the disease process and guide targeted management.

3

Evaluate the maternal and fetal clinical status to determine the urgency and type of intervention required.

The mother is symptomatic (tachycardia, dyspnea) with a critically low hemoglobin of

6.8

g/dL, leading to secondary fetal compromise (fetal tachycardia, minimal variability).

Fetal distress in this context is secondary to maternal hypoxia; thus, maternal resuscitation is the absolute priority.

4

Select the most appropriate definitive management.

Discontinue the oxidative drug (nitrofurantoin) and administer a packed red blood cell transfusion to correct the oxygen-carrying deficit.

Stopping the offending agent halts further hemolysis, while a blood transfusion treats the severe symptomatic anemia and serves as effective intrauterine resuscitation.

Key Concept

Diagnosis and management of acute hemolytic anemia due to Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency, including the recognition of oxidative triggers and the provision of appropriate supportive care.

Estimated Time:2m 0s

Question 12Question →

Match the following classic peripheral blood smear findings with their most likely associated hematologic diagnosis.

Click a left item, then click its matching right item

Show answer & explanation

Answer

Heinz bodies and bite cells are matched with G6PD deficiency; hypersegmented neutrophils with megaloblastic anemia; smudge cells with chronic lymphocytic leukemia; Auer rods with acute myeloid leukemia; and schistocytes with thrombotic thrombocytopenic purpura.

Each peripheral smear finding is pathognomonic or highly characteristic for a specific hematologic disorder based on its underlying pathophysiology (e.g., oxidative stress, impaired DNA synthesis, cell fragility, abnormal lysosomes, or intravascular shearing).

Step-by-Step Solution

1

Evaluate Heinz bodies and bite cells

Matched with Glucose-6-phosphate dehydrogenase (G6PD) deficiency

Oxidative damage to hemoglobin is the primary mechanism in G6PD deficiency, leading to the formation of Heinz bodies and subsequent bite cells.

2

Evaluate Hypersegmented neutrophils

Matched with Megaloblastic anemia

Impaired DNA synthesis causes abnormal nuclear maturation, leading to multi-lobed neutrophils.

3

Evaluate Smudge cells

Matched with Chronic lymphocytic leukemia

The malignant lymphocytes in this leukemia are unusually fragile and break apart on the glass slide during smear preparation.

4

Evaluate Auer rods

Matched with Acute myeloid leukemia

These specific cytoplasmic inclusions are only found in cells of the myeloid lineage, specifically myeloblasts.

5

Evaluate Schistocytes

Matched with Thrombotic thrombocytopenic purpura

Intravascular microthrombi mechanically shear passing red blood cells, creating these characteristic fragments.

Key Concept

Identifying characteristic peripheral blood smear findings is essential for the rapid diagnosis of underlying hematologic and oncologic disorders.

Question 13Question →

A hospital rapid response team is called to the bedside of a 58-year-old female inpatient due to acute right leg pain and swelling. The patient was admitted six days ago for an acute non-ST-segment elevation myocardial infarction and has been receiving a continuous intravenous infusion of unfractionated heparin since admission. Her other medications include aspirin, atorvastatin, and metoprolol. Temperature is 37.1°C (98.8°F), blood pressure is 135/85 mmHg, pulse is 92/min, and respirations are 16/min. Physical examination of the right lower extremity reveals significant edema from the calf to the mid-thigh with localized tenderness, but peripheral pulses remain palpable. Laboratory results on admission showed a platelet count of 260,000/mm³. Today's laboratory studies reveal a hemoglobin of 13.1 g/dL, leukocyte count of 8,200/mm³, and a platelet count of 65,000/mm³. A stat lower extremity compression ultrasonography confirms a new, occlusive deep venous thrombosis in the right femoral vein. Which of the following is the most appropriate next step in the management of this patient?

Discontinue unfractionated heparin and initiate an argatroban infusion

Discontinue unfractionated heparin and initiate oral warfarin therapy

Discontinue unfractionated heparin and administer subcutaneous enoxaparin

Continue unfractionated heparin and administer a prophylactic platelet transfusion

Order a serotonin release assay and maintain the current heparin infusion pending results

Show answer & explanation

Answer: Discontinue unfractionated heparin and initiate an argatroban infusion

Answer

The most appropriate next step is to discontinue all heparin products and initiate a direct thrombin inhibitor, such as argatroban.

The patient's clinical picture is highly characteristic of Heparin-Induced Thrombocytopenia (HIT) Type 2. She has a precipitous (>50%) drop in platelets occurring 5 to 10 days after heparin exposure, complicated by a new thrombotic event (femoral DVT). HIT is caused by IgG autoantibodies targeting complexes of heparin and Platelet Factor 4 (PF4), which leads to widespread platelet activation and consumption. When clinical suspicion is high (indicated by a high 4T score), all forms of heparin must be stopped immediately. To manage the ongoing hypercoagulable state and the new DVT, a non-heparin alternative anticoagulant must be initiated promptly. Direct thrombin inhibitors like argatroban or bivalirudin, or the factor Xa inhibitor fondaparinux, are the agents of choice.

Step-by-Step Solution

1

Analyze the patient's presentation and timeline.

The patient developed a >50% drop in platelet count (from 260,000 to 65,000) occurring exactly 6 days after the initiation of unfractionated heparin.

Establishing the timeline and magnitude of thrombocytopenia is required to calculate the 4T score for suspected Heparin-Induced Thrombocytopenia (HIT).

2

Assess for complications of the thrombocytopenia.

The patient has concurrently developed a new deep venous thrombosis (DVT) in the right femoral vein.

HIT is paradoxically a highly prothrombotic state; the presence of a new thrombosis makes the clinical diagnosis of HIT Type 2 extremely likely.

3

Determine the necessary immediate therapeutic intervention.

All forms of heparin must be immediately discontinued, and an alternative, non-heparin anticoagulant must be started to treat the active DVT.

Continuing heparin or delaying treatment fuels the immune-mediated thrombosis. Argatroban (a direct thrombin inhibitor) is a preferred alternative anticoagulant in this scenario.

Key Concept

Patients with a high clinical suspicion for Heparin-Induced Thrombocytopenia (HIT) Type 2 must have all heparin products immediately discontinued and an alternative non-heparin anticoagulant (e.g., argatroban, fondaparinux) started empirically.

Question 14Question →

Match each patient's clinical presentation of an oncologic or hematologic emergency with the most appropriate immediate medical intervention.

Click a left item, then click its matching right item

Show answer & explanation

Answer

Acute Promyelocytic Leukemia requires immediate ATRA; Epidural Spinal Cord Compression requires immediate dexamethasone; Neutropenic Fever requires prompt empiric cefepime; Tumor Lysis Syndrome requires rasburicase and vigorous hydration.

Each presentation describes a classic oncologic emergency that dictates a specific, immediate pharmacologic intervention to prevent irreversible morbidity or mortality. Matching correctly demonstrates mastery of acute management protocols.

Step-by-Step Solution

1

Analyze the first vignette (pancytopenia, coagulopathy, promyelocytes with Auer rods).

Diagnosis is Acute Promyelocytic Leukemia (APL) with DIC.

Recognizing APL is critical because it carries a high risk of fatal hemorrhage if not immediately treated with the differentiating agent, ATRA.

2

Analyze the second vignette (prostate cancer, lower extremity weakness, sensory level, urinary retention).

Diagnosis is Malignant Epidural Spinal Cord Compression.

The sudden onset of neurologic deficits requires immediate mitigation of spinal cord edema using high-dose corticosteroids before obtaining definitive imaging.

3

Analyze the third vignette (chemotherapy, fever

>38.3^\circ \text{C}

, ANC

<500/\mu\text{L}

).

Diagnosis is Febrile Neutropenia.

Febrile neutropenia is a medical emergency requiring rapid administration of anti-pseudomonal beta-lactams to prevent lethal septic shock.

4

Analyze the fourth vignette (Burkitt lymphoma, hyperuricemia, hyperkalemia, elevated creatinine).

Diagnosis is Spontaneous Tumor Lysis Syndrome.

Rapid degradation of established hyperuricemia with rasburicase is essential to prevent permanent acute renal failure prior to massive cell lysis from chemotherapy.

Key Concept

Recognition and emergent pharmacological management of acute oncologic and hematologic emergencies.

Estimated Time:2m 0s

Question 15Question →

A 65-year-old man presents to the clinic with a 4-month history of progressive fatigue, shortness of breath on exertion, and frothy urine. Physical examination reveals periorbital purpura, an enlarged tongue with lateral indentations, and 2+ pitting edema of the lower extremities. Jugular venous distention is present. Echocardiography demonstrates thickened left and right ventricular walls with a sparkling, granular appearance and an ejection fraction of 55%. Urinalysis shows 4+ proteinuria, and a 24-hour urine collection confirms 5.2 g of protein. Suspecting an underlying hematologic disorder, the physician plans a diagnostic and therapeutic workup.

Arrange the following steps in the most appropriate chronological sequence for the definitive diagnosis and management of this patient's condition.

Drag items to arrange them in the correct order

Show answer & explanation

Answer

The correct sequence is: (1) Screen for a monoclonal protein, (2) Obtain a tissue biopsy for Congo red staining, (3) Determine the specific amyloid fibril type, and (4) Initiate clone-directed systemic chemotherapy.

The standard diagnostic pathway for suspected AL amyloidosis begins with non-invasive identification of the monoclonal protein burden (immunofixation and SFLC). This is followed by histologic confirmation of amyloid deposition (tissue biopsy with Congo red stain). Crucially, the amyloid MUST then be typed (via mass spectrometry or immunohistochemistry) to definitively differentiate AL from ATTR or AA types, as clinical presentations can overlap (especially cardiomyopathy). Only after AL typing is confirmed can clone-directed chemotherapy be safely and appropriately initiated.

Step-by-Step Solution

1

Recognize the clinical syndrome of AL (Primary) Amyloidosis.

The patient has pathognomonic signs of AL amyloidosis, including periorbital purpura, macroglossia, restrictive cardiomyopathy, and nephrotic syndrome.

Identifying the clinical pattern sets the pre-test probability and dictates the need for a specific diagnostic algorithm targeting a plasma cell dyscrasia.

2

Screen for the underlying abnormal protein.

Order serum and urine immunofixation electrophoresis and a serum free light chain (SFLC) assay.

AL amyloidosis is caused by a plasma cell clone producing monoclonal light chains. This non-invasive screening is highly sensitive and establishes the presence of the suspected dyscrasia.

3

Confirm tissue deposition of amyloid.

Perform an abdominal fat pad aspiration or target organ biopsy with Congo red staining.

A positive Congo red stain demonstrating apple-green birefringence under polarized light is the gold standard to confirm the presence of amyloid tissue deposits.

4

Type the specific amyloid fibril.

Use mass spectrometry or specific immunohistochemistry on the biopsied tissue.

Congo red positivity only confirms 'amyloidosis'. It does not differentiate AL from ATTR (transthyretin) or AA amyloidosis. Typing is strictly required before initiating therapy.

5

Initiate definitive therapy based on the typed fibril.

Start clone-directed systemic chemotherapy (e.g., bortezomib, cyclophosphamide, dexamethasone).

Once AL amyloidosis is confirmed and typed, chemotherapy is used to eradicate the offending plasma cell clone and halt the progression of organ damage.

Key Concept

Diagnostic and therapeutic algorithm for Primary (AL) Amyloidosis.

Question 16Question →

A 71-year-old man is evaluated in the clinic for a 3-month history of worsening lower back pain and generalized fatigue. The pain is deep, achy, and localized to the mid-lumbar region without radiation to the legs. He also reports new-onset constipation and increased frequency of urination. He has no significant past medical history and takes no medications. His temperature is $37.0^\circ\text{C}$ ( $98.6^\circ\text{F}$ ), blood pressure is $142/88$ mmHg, pulse is $84$ /min, and respiratory rate is $14$ /min. Physical examination shows midline point tenderness over the L4 vertebra. Neurologic examination of the lower extremities shows $5/5$ strength with normal deep tendon reflexes.

Laboratory results are as follows:

Laboratory Test	Result
Hemoglobin	$9.1$ g/dL
Leukocytes	$6,800/\text{mm}^3$
Platelets	$210,000/\text{mm}^3$
Blood urea nitrogen	$38$ mg/dL
Serum creatinine	$2.2$ mg/dL
Serum calcium	$11.9$ mg/dL
Total serum protein	$9.2$ g/dL
Serum albumin	$3.5$ g/dL

Which of the following is the most appropriate next step in the diagnostic evaluation of this patient?

Intact parathyroid hormone level

Measurement of serum prostate-specific antigen

Radionuclide bone scan

Serum and urine protein electrophoresis

Renal ultrasonography

Show answer & explanation

Answer: Serum and urine protein electrophoresis

Answer

Serum and urine protein electrophoresis

This patient's clinical presentation is highly suspicious for multiple myeloma, characterized by the CRAB criteria (hyperCalcemia, Renal insufficiency, Anemia, Bone lytic lesions). A critical diagnostic clue is the significant protein gap (total serum protein minus serum albumin

> 4

g/dL), which strongly suggests the presence of a circulating monoclonal immunoglobulin (M-protein). The most appropriate initial step to evaluate for a monoclonal gammopathy is serum and urine protein electrophoresis (SPEP and UPEP), often combined with immunofixation. If a monoclonal spike is detected, a bone marrow biopsy is subsequently performed to confirm the diagnosis.

Step-by-Step Solution

1

Analyze the clinical presentation and physical examination.

An elderly man presents with progressive lower back pain, bony tenderness, fatigue, polyuria, and constipation.

To identify key symptoms that suggest a systemic oncologic or endocrine condition rather than isolated mechanical back pain.

2

Evaluate the laboratory panel for specific diagnostic clues.

The patient has anemia, acute kidney injury (elevated BUN/creatinine), severe hypercalcemia, and a massive protein gap (Total protein

9.2

- Albumin

3.5

=

5.7

g/dL).

To synthesize the findings into a unifying diagnosis, recognizing the classic CRAB criteria (hyperCalcemia, Renal insufficiency, Anemia, Bone lesions) of multiple myeloma.

3

Determine the most appropriate initial diagnostic test.

The constellation of findings is highly suspicious for multiple myeloma. The initial test of choice to identify the underlying monoclonal gammopathy is serum and urine protein electrophoresis.

To confirm the presence of an M-spike (monoclonal protein) before proceeding to definitive bone marrow biopsy.

Key Concept

The classic presentation of multiple myeloma includes the CRAB criteria (hyperCalcemia, Renal insufficiency, Anemia, Bone lytic lesions) alongside a significant protein gap (>4 g/dL). Initial diagnosis requires identification of a monoclonal protein using serum and urine protein electrophoresis.

Estimated Time:1m 15s

Question 17Question →

A $42$ -year-old woman is brought to the emergency department by her husband due to progressive confusion, lethargy, and a low-grade fever over the past $24$ hours. She has no significant past medical history. Her temperature is $37.8^\circ\text{C}$ ( $100.0^\circ\text{F}$ ), blood pressure is $142/88$ mmHg, and pulse is $105$ /min. Physical examination reveals petechiae on her lower extremities and scleral icterus. Neurologic examination shows a lethargic patient who is oriented only to person.

Laboratory studies show:

Test	Result
Hemoglobin	$8.2$ g/dL
Platelets	$22,000$ /mm $^3$
Leukocytes	$8,500$ /mm $^3$
Creatinine	$1.8$ mg/dL
Total bilirubin	$3.2$ mg/dL
Indirect bilirubin	$2.8$ mg/dL
Lactate dehydrogenase	$850$ U/L

Arrange the following steps in the most appropriate chronological order for the management of this patient.

Drag items to arrange them in the correct order

Show answer & explanation

Answer

The correct sequence is: 1) Perform a peripheral blood smear to identify schistocytes, 2) Obtain a baseline blood sample for ADAMTS13 activity, 3) Initiate emergent therapeutic plasma exchange (PEX), and 4) Monitor platelet count and lactate dehydrogenase (LDH) daily to assess treatment response.

The patient's presentation of thrombocytopenia, hemolytic anemia, renal dysfunction, neurologic changes, and fever is highly suggestive of Thrombotic Thrombocytopenic Purpura (TTP). The first step is to confirm microangiopathic hemolytic anemia (MAHA) via a peripheral blood smear showing schistocytes. Once MAHA and thrombocytopenia are confirmed without another obvious cause, a presumptive diagnosis of TTP is made. Before administering any plasma, a blood sample for ADAMTS13 activity must be drawn, as donor plasma will alter baseline levels. Following this, therapeutic plasma exchange (PEX) must be initiated emergently. It is the primary life-saving treatment and should not be delayed while awaiting ADAMTS13 results. Finally, the patient's response to PEX and adjunctive immunosuppression is monitored daily by following the platelet count and LDH levels.

Step-by-Step Solution

1

Identify the clinical syndrome

Suspected Thrombotic Thrombocytopenic Purpura (TTP)

The patient presents with the classic pentad: fever, neurologic changes, thrombocytopenia, hemolytic anemia, and renal dysfunction.

2

Select the initial diagnostic test

Peripheral blood smear

Visualizing schistocytes confirms microangiopathic hemolytic anemia (MAHA), establishing the presumptive diagnosis of TTP.

3

Identify the necessary pre-treatment laboratory draw

ADAMTS13 activity and inhibitor assay

Blood must be drawn before giving donor plasma to accurately measure the patient's baseline enzyme activity.

4

Select the emergent definitive therapy

Therapeutic plasma exchange (PEX)

PEX removes autoantibodies and replenishes ADAMTS13; it must be started immediately without waiting for confirmatory assay results.

5

Determine the follow-up monitoring strategy

Daily monitoring of platelets and LDH

These markers indicate the resolution of microthrombi and hemolysis, guiding the duration of PEX.

Key Concept

Sequential management of suspected Thrombotic Thrombocytopenic Purpura (TTP)

Estimated Time:1m 30s

Question 18Question →

A 68-year-old man with a history of metastatic prostate cancer is brought to the emergency department by his wife due to a 2-day history of progressively worsening lower back pain and new-onset difficulty walking. This morning, he also experienced an episode of urinary incontinence. Vital signs are within normal limits. Neurologic examination shows 3/5 strength in both lower extremities, diminished pinprick sensation below the T10 dermatome, and bilateral Babinski signs. Anal sphincter tone is markedly decreased. Arrange the following management steps in the most appropriate chronological order for this patient.

Drag items to arrange them in the correct order

Show answer & explanation

Answer

The correct sequence of management for malignant epidural spinal cord compression is to first administer intravenous dexamethasone, followed by an MRI of the entire spine, then obtain surgical and oncology consultations, and finally perform definitive decompression or radiotherapy.

The standard protocol for managing suspected malignant epidural spinal cord compression with objective neurologic deficits (e.g., motor weakness, sphincter dysfunction) prioritizes preserving neurologic function. High-dose intravenous dexamethasone reduces spinal cord edema and must be given immediately upon clinical suspicion. After medical stabilization, an MRI of the entire spine is required to confirm the diagnosis and delineate the anatomic extent of the disease. Once the lesion is localized, specialist consultation dictates the appropriate definitive intervention, which typically involves surgical decompression followed by radiation, or radiation therapy alone.

Step-by-Step Solution

1

Recognize the oncologic emergency

Clinical diagnosis of malignant epidural spinal cord compression (MESCC) based on back pain, lower extremity weakness, and bowel/bladder dysfunction in a patient with metastatic prostate cancer.

Early recognition is crucial because functional outcome is directly related to the neurologic status at the time treatment is initiated.

2

Administer high-dose corticosteroids immediately

Intravenous dexamethasone is given before any imaging studies are performed.

Corticosteroids decrease vasogenic edema around the spinal cord, relieving pressure and potentially preventing irreversible ischemic damage.

3

Obtain definitive neuroimaging

An MRI of the entire spine without and with contrast is performed.

MRI is the gold standard for diagnosing MESCC, identifying the exact level of compression, and ruling out additional subclinical epidural metastases.

4

Determine and execute definitive therapy

Consultation with specialists leads to surgical decompression or external beam radiotherapy.

Definitive treatment removes or shrinks the tumor to provide long-term relief of cord compression, depending on tumor radiosensitivity and patient surgical risk.

Key Concept

Algorithm for the diagnosis and management of malignant epidural spinal cord compression

Estimated Time:1m 0s

Question 19Question →

A $38$ -year-old man is brought to the emergency department due to a severe nosebleed that has not stopped for $2$ hours, along with bleeding gums and profound fatigue over the past week. His temperature is $37.8^\circ\text{C}$ ( $100.0^\circ\text{F}$ ), blood pressure is $110/70$ mm Hg, and heart rate is $112$ /min. Physical examination reveals diffuse petechiae across his chest and large ecchymoses on his extremities. Laboratory studies show:

Complete Blood Count	Value
Hemoglobin	$8.2$ g/dL
Leukocyte count	$2,100/\text{mm}^3$
Platelet count	$18,000/\text{mm}^3$

Coagulation Profile	Value
Prothrombin time (PT)	$22$ seconds
Activated partial thromboplastin time (aPTT)	$55$ seconds
Fibrinogen	$75$ mg/dL
D-dimer	$>10,000$ ng/mL

A peripheral blood smear reveals pancytopenia and several large, atypical promyelocytes containing multiple needle-like intracytoplasmic inclusions.

Arrange the following steps in the most appropriate chronological order for the optimal management of this patient's condition.

Drag items to arrange them in the correct order

Show answer & explanation

Answer

The correct sequence is: 1) Empirical administration of all-trans retinoic acid (ATRA), 2) Bone marrow aspiration and biopsy, 3) Molecular confirmation of the PML::RARA fusion gene, 4) Addition of arsenic trioxide (ATO) to the treatment regimen.

Acute promyelocytic leukemia (APL) is a medical emergency that presents with pancytopenia and severe coagulopathy (DIC), driven by the release of procoagulants from leukemic promyelocytes. The first and most critical step is the empirical administration of all-trans retinoic acid (ATRA). ATRA induces differentiation of the malignant promyelocytes into mature neutrophils, which rapidly halts the coagulopathy and prevents fatal bleeding. Because of the high risk of early mortality from hemorrhage, ATRA must be given as soon as APL is suspected based on peripheral smear morphology (e.g., atypical promyelocytes with Auer rods), without waiting for definitive diagnostic tests. After ATRA is initiated and supportive care (e.g., cryoprecipitate, platelets) is provided, a bone marrow aspiration and biopsy is performed. The obtained marrow sample is then used for molecular confirmation via FISH or PCR to identify the pathognomonic t(15;17) translocation (PML::RARA fusion gene). Once the diagnosis is definitively confirmed and the patient's risk profile is established, arsenic trioxide (ATO) and/or chemotherapy is added to ATRA to complete the definitive induction treatment regimen.

Step-by-Step Solution

1

Recognize the clinical presentation of Acute Promyelocytic Leukemia (APL).

The patient has pancytopenia, bleeding, DIC (low fibrinogen, elevated PT/aPTT/D-dimer), and atypical promyelocytes with Auer rods (needle-like inclusions).

Identifying APL is critical because it is a hematologic emergency requiring immediate specific intervention.

2

Determine the immediate next step in management.

Empirical initiation of ATRA is required as the very first step.

ATRA promotes differentiation of the leukemic promyelocytes, rapidly reversing the severe coagulopathy and preventing fatal hemorrhage. It must not be delayed for confirmatory testing.

3

Identify the proper sequence of diagnostic confirmation.

Bone marrow biopsy is performed to obtain the necessary sample, followed by molecular testing (FISH/PCR) on that sample.

Definitive diagnosis requires identifying the t(15;17) translocation, but the tissue must first be safely collected via biopsy.

4

Determine the definitive treatment step.

Add ATO (and sometimes anthracyclines, depending on risk stratification) to complete the induction regimen.

Once the diagnosis is genetically confirmed and risk is stratified, standard definitive induction therapy is implemented.

Key Concept

In patients with suspected acute promyelocytic leukemia (APL), all-trans retinoic acid (ATRA) must be initiated immediately to prevent fatal hemorrhage from disseminated intravascular coagulation (DIC), prior to obtaining a bone marrow biopsy and awaiting molecular confirmation.

Estimated Time:1m 30s

Question 20Question →

Match each patient's clinical presentation with the most appropriate confirmatory diagnostic test.

Click a left item, then click its matching right item

Show answer & explanation

Answer

The presentations match as follows: SLE with spherocytes matches Direct antiglobulin test; Pancytopenia with portal vein thrombosis matches Flow cytometry for CD55 and CD59; Hemolysis post-nitrofurantoin matches G6PD enzyme assay; Pigment gallstones with high MCHC matches EMA binding test; Altered mental status with schistocytes matches ADAMTS13 activity assay.

Each clinical presentation contains classic pathognomonic findings that map to a highly specific diagnostic test for a particular hematologic disorder. The SLE patient with spherocytes has AIHA (Direct Coombs). The patient with pancytopenia and portal vein thrombosis has PNH (CD55/CD59). The patient with acute hemolysis after nitrofurantoin has G6PD deficiency (G6PD assay). The adolescent with pigment gallstones and high MCHC has hereditary spherocytosis (EMA binding). The patient with schistocytes, thrombocytopenia, and confusion has TTP (ADAMTS13).

Step-by-Step Solution

1

Analyze the first clinical presentation

SLE patient with hemolysis and spherocytes suggests warm autoimmune hemolytic anemia.

Systemic autoimmune diseases often produce IgG autoantibodies directed against red blood cell antigens.

2

Analyze the second clinical presentation

Pancytopenia, atypical venous thrombosis, and hemolysis point to paroxysmal nocturnal hemoglobinuria (PNH).

An acquired stem cell mutation leads to a lack of GPI anchors, making red blood cells highly susceptible to complement-mediated destruction.

3

Analyze the third clinical presentation

Hemolysis after a classic trigger (nitrofurantoin) with bite cells indicates Glucose-6-phosphate dehydrogenase deficiency.

Decreased NADPH production leads to oxidative damage of hemoglobin when exposed to specific medications or infections.

4

Analyze the fourth clinical presentation

A young patient with pigment gallstones, splenomegaly, and high MCHC suggests hereditary spherocytosis.

An inherited structural membrane defect leads to red blood cell dehydration, increasing the MCHC and causing splenic destruction.

5

Analyze the fifth clinical presentation

Thrombocytopenia, schistocytes, renal injury, and neurologic changes classically describe thrombotic thrombocytopenic purpura (TTP).

Microthrombi form systemically due to uncleaved, ultra-large von Willebrand factor multimers.

Key Concept

Clinical presentations and confirmatory diagnostics of hemolytic anemias and thrombotic microangiopathies

Hematology and Oncology

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