Hematology Practice Questions

Q: A 55-year-old woman presents with fatigue, pallor, and jaundice. Laboratory tests show hemoglobin of 8.5 g/dL, a reticulocyte count of 6%, and an indirect bilirubin level of 3.5 mg/dL. Which test is most likely to confirm the diagnosis?

Direct Coombs test. ***Direct Coombs test*** - The patient's symptoms (fatigue, pallor, jaundice) combined with laboratory findings (**anemia**, **reticulocytosis**, **indirect hyperbilirubinemia**) are highly suggestive of **hemolytic anemia** [1],[2]. - A **Direct Coombs test** (Direct Antiglobulin Test or DAT) is used to detect antibodies or complement components bound to the surface of red blood cells, which is the hallmark of **autoimmune hemolytic anemia** [1]. *Serum ferritin* - **Serum ferritin** measures iron stores and would be relevant for diagnosing **iron deficiency anemia**. - However, the presence of **jaundice** and **reticulocytosis** points away from iron deficiency and towards a hemolytic process. *Hemoglobin electrophoresis* - **Hemoglobin electrophoresis** is used to identify abnormal hemoglobin variants and diagnose conditions like **sickle cell anemia** or **thalassemia**. - While these can cause hemolytic anemia, the acute presentation with clear signs of red blood cell destruction (jaundice, reticulocytosis) in an adult often warrants investigation for an acquired cause like **autoimmune hemolytic anemia** first [1]. *Bone marrow biopsy* - A **bone marrow biopsy** is invasive and typically reserved for investigating disorders of hematopoiesis, such as bone marrow failure syndromes or hematologic malignancies. - While it can assess red blood cell production, it is not the primary diagnostic test for identifying the cause of active **hemolysis**.

Q: A 65-year-old man presents with cyanosis, confusion, and a pulse oximetry reading of 85% despite receiving supplemental oxygen. What is the most likely cause of his hypoxia?

Methemoglobinemia. ***Methemoglobinemia*** - **Cyanosis** and **confusion** in the presence of hypoxia refractory to **supplemental oxygen** suggest **methemoglobinemia** [1]. - In this condition, iron in heme is oxidized to the ferric state, impairing **oxygen binding** and causing a left shift in the oxygen dissociation curve, reducing oxygen delivery to tissues. *Pulmonary embolism* - While pulmonary embolism can cause acute shortness of breath and hypoxia, it typically responds to supplemental oxygen, especially if the ventilation-perfusion mismatch is not severe [2]. - Cyanosis and decreased mental status are usually seen in massive pulmonary embolism, but the **refractoriness to oxygen** is less characteristic than in methemoglobinemia [2]. *Congestive heart failure* - Worsening heart failure can cause hypoxemia due to **pulmonary edema** and impaired gas exchange, often presenting with dyspnea, orthopnea, and crackles. - However, the hypoxia is usually responsive to oxygen supplementation, and severe cyanosis and confusion refractory to oxygen are less typical presentations compared to methemoglobinemia [2]. *Chronic obstructive pulmonary disease* - Patients with severe COPD can have baseline hypoxia and hypercapnia, but the acute development of severe cyanosis and confusion with **hypoxia refractory to oxygen** is more concerning for an alternative cause. - While exacerbations can cause worsened oxygenation, the described clinical picture, particularly the persistence of hypoxia despite oxygen, points away from uncomplicated COPD exacerbation [2].

Q: A 40-year-old woman with a history of systemic lupus erythematosus (SLE) presents with acute onset of dyspnea and pleuritic chest pain. A chest CT shows multiple bilateral pulmonary emboli. What is the most likely underlying cause?

Antiphospholipid syndrome. Detailed assessment of a patient with SLE presenting with acute dyspnea and pleuritic pain involves ruling out common complications. ***Antiphospholipid syndrome*** - Patients with **SLE** have a high prevalence of **antiphospholipid antibodies**, which significantly increase the risk of both arterial and venous **thrombosis**, including **pulmonary emboli** [1]. - The combination of a history of SLE and acute thrombotic events like **pulmonary embolism** makes antiphospholipid syndrome the most likely underlying cause. *Infective endocarditis* - While infective endocarditis can cause septic emboli, typically from vegetations, it usually presents with fever, new heart murmurs, and signs of infection, which are not mentioned in this patient's presentation. - The emboli in infective endocarditis are usually sterile or septic microemboli, rather than large **pulmonary emboli** typically seen in thrombotic disorders. *Pulmonary hypertension* - Pulmonary hypertension can cause dyspnea and chest pain, but it is a consequence of structural or functional changes in the pulmonary vasculature, not a direct cause of acute **pulmonary emboli**. - While chronic recurrent pulmonary emboli can lead to **chronic thromboembolic pulmonary hypertension (CTEPH)**, the acute presentation described points to the emboli themselves as the primary event. *Congestive heart failure* - Congestive heart failure causes dyspnea and can be associated with chest pain, but the primary pathology involves impaired cardiac function leading to fluid overload and pulmonary congestion, not multiple **pulmonary emboli**. - A CT scan showing **pulmonary emboli** specifically points away from congestive heart failure as the primary cause of the acute symptoms in this context.

Q: A 25-year-old woman presents with episodic hemolysis and hemoglobinuria, particularly at night. What is the most likely diagnosis?

Paroxysmal nocturnal hemoglobinuria. Paroxysmal nocturnal hemoglobinuria - This condition is characterized by episodic hemolysis and hemoglobinuria, often worse at night due to increased blood acidity during sleep. - It is caused by a deficiency in GPI-anchored proteins (like CD55 and CD59) on red blood cells, making them susceptible to complement-mediated lysis. G6PD deficiency - While it causes hemolysis, it is typically triggered by oxidative stress from certain foods (e.g., fava beans) or drugs, not specifically worse at night [1]. - Laboratory findings would show Heinz bodies and bite cells following an oxidative challenge, which are not characteristic of the nocturnal pattern described [3]. Hereditary spherocytosis - This is a chronic hemolytic anemia characterized by spherocytes on a peripheral smear and increased osmotic fragility of red blood cells [2]. - Hemolysis is generally continuous, not episodic or specifically nocturnal, and is due to structural defects in the red cell membrane [4]. Sickle cell disease - This condition involves sickle-shaped red blood cells under hypoxic conditions, leading to vaso-occlusive crises and chronic hemolysis. - While it causes episodic symptoms, these are typically painful crises and organ damage, not primarily characterized by nocturnal hemoglobinuria.

Q: What is a common early sign of vitamin B12 deficiency?

Glossitis. ***Glossitis*** - **Glossitis**, or inflammation of the tongue, characterized by a **smooth, beefy-red appearance**, is a common early manifestation of vitamin B12 deficiency due to rapid cell turnover in the oral mucosa [1]. - Reduced **erythrocyte production** resulting from B12 deficiency leads to impaired oxygen delivery to tissues, contributing to tongue changes and discomfort. *Jaundice* - **Jaundice** typically occurs in conditions involving increased **bilirubin** levels, such as liver disease or hemolytic anemia, which are not direct or early features of vitamin B12 deficiency. - While **cobalamin deficiency** can cause **hemolysis** leading to inefficient erythropoiesis, overt jaundice is less frequent as an initial sign. *Pallor* - **Pallor**, a pale complexion, is a general sign of **anemia**, which can result from vitamin B12 deficiency [1]. However, it is a less specific early sign than glossitis, as it can occur in many types of anemia. - The anemia associated with B12 deficiency is typically **macrocytic**, characterized by abnormally large red blood cells, which contributes to pallor [2] but may develop gradually. *Peripheral neuropathy* - **Peripheral neuropathy**, involving symptoms like numbness, tingling, or weakness, is a significant neurological manifestation of chronic vitamin B12 deficiency but usually develops later [2]. - Early stages of B12 deficiency often present with more subtle hematological or gastrointestinal signs before neurological damage becomes apparent.

Q: A 65-year-old woman presents with progressive fatigue and abdominal discomfort. Imaging reveals massive splenomegaly. A bone marrow aspirate shows myeloid cells with the Philadelphia chromosome. What is the first-line treatment for this condition?

Imatinib. ***Imatinib*** - The presence of the **Philadelphia chromosome** (BCR-ABL fusion gene) in a patient with progressive fatigue, abdominal discomfort, and massive splenomegaly is characteristic of **Chronic Myeloid Leukemia (CML)**. - **Imatinib** is a **tyrosine kinase inhibitor (TKI)** that specifically targets the BCR-ABL protein, making it the highly effective and universally accepted first-line treatment for CML [1]. *All-trans retinoic acid* - **All-trans retinoic acid (ATRA)** is a retinoid derivative used to treat **Acute Promyelocytic Leukemia (APL)**. - It works by inducing differentiation of leukemic promyelocytes but is ineffective for CML. *Hydroxyurea* - **Hydroxyurea** is a myelosuppressive agent used to reduce high white blood cell counts in **CML**, especially in the **blastic phase** or to manage severe symptoms [1]. - While it can control cell counts, it does not target the underlying genetic abnormality (Philadelphia chromosome) and is not considered first-line curative therapy [1]. *Rituximab* - **Rituximab** is a **monoclonal antibody** that targets the **CD20 protein** on B lymphocytes, used in the treatment of **B-cell non-Hodgkin lymphoma** and some autoimmune diseases. - It has no role in the direct treatment of CML, which is a myeloid malignancy [2].

Q: A 55-year-old man presents with fatigue and shortness of breath. Laboratory results reveal normocytic anemia and increased reticulocytes. Which condition is most consistent with these findings?

Hemolytic anemia. ***Hemolytic anemia*** - The presence of **normocytic anemia** along with **increased reticulocytes** indicates the bone marrow is compensating for red blood cell destruction, typical of hemolytic anemia. - Symptoms like **fatigue and shortness of breath** are common due to decreased oxygen-carrying capacity from the anemia. *Pernicious anemia* - This condition typically presents with **macrocytic anemia** and may have neurological symptoms due to vitamin B12 deficiency, differing from normocytic findings. - It is not associated with elevated reticulocyte counts, as red blood cell production is impaired rather than compensatory. *Iron deficiency anemia* [1] - Iron deficiency anemia usually results in **microcytic anemia** and low reticulocyte counts, contrasting with the findings in this patient [1]. - Symptoms may include **fatigue and pallor**, but the laboratory changes do not align with normocytic anemia or increased reticulocytes. *Aplastic anemia* - Aplastic anemia leads to a **pancytopenia** (low blood cell counts across the board) rather than just anemia, with reticulocytes often being **low or absent**. - Symptoms involve severe fatigue and increased susceptibility to infections and bleeding, which differ from isolated anemia symptoms.

Q: A 32-year-old woman presents with fever, fatigue, jaundice, and anemia. Laboratory results show hemoglobin of 7.5, a high reticulocyte count, and elevated indirect bilirubin. The peripheral smear reveals spherocytes. What is the definitive treatment?

Corticosteroids. Corticosteroids - The presented symptoms (fever, fatigue, jaundice, anemia with high reticulocytes, elevated indirect bilirubin, and spherocytes) are highly suggestive of warm autoimmune hemolytic anemia (AIHA) [1]. - Corticosteroids are the first-line and often definitive treatment, suppressing the immune system and reducing antibody production against red blood cells. Splenectomy - Splenectomy is considered a second-line treatment option if corticosteroids fail or if the patient requires unacceptably high doses for maintenance. - It removes the primary site of red blood cell destruction but is not the initial definitive treatment. Blood transfusion - Blood transfusion is a supportive measure used to manage severe anemia and stabilize the patient, but it does not address the underlying autoimmune process. - While helping with symptoms, it is not a definitive treatment for the autoimmune destruction of red blood cells. Immunosuppressive therapy - While corticosteroids are a type of immunosuppressive therapy, other forms of immunosuppressive therapy (e.g., rituximab, azathioprine, cyclophosphamide) are typically reserved for cases refractory to corticosteroids and splenectomy [2]. - They are not considered the initial definitive treatment for warm AIHA.

Q: In which condition are multiple lytic lesions typically seen?

Multiple myeloma. ***Multiple myeloma*** - Characterized by **solitary lytic bone lesions** [1], often seen on X-rays, indicating areas of bone destruction [1]. - It is associated with **monoclonal proliferation** of plasma cells [1], leading to both osteolytic lesions and hypercalcemia. *Osteoblast* - Involvement of osteoblasts typically leads to **bone formation**, not lytic lesions. - Conditions like **osteosarcoma** may show lytic lesions, but not from osteoblast activity directly. *Mitral stenosis* - Primarily a **valvular heart disease**, leading to **blood flow obstruction**, not associated with lytic bone lesions. - Symptoms are predominantly related to **cardiac function** rather than bone pathology. *Atherosclerosis* - A vascular condition characterized by **plaque formation** within arteries, affecting blood flow but not leading to bone lesions. - It manifests as cardiovascular diseases, not as **osseous lesions**.

Question 1

A 60-year-old male presents with fatigue, anemia, and splenomegaly. His peripheral blood smear shows teardrop-shaped red blood cells. Which of the following physiological mechanisms is most likely responsible for his anemia?

Accepted Answer

Decreased red blood cell lifespan due to splenic sequestration

Answer

Increased iron absorption in the gut

Answer

Decreased erythropoietin production in the kidneys

Answer

Increased erythropoiesis response

Question 2

A 55-year-old woman presents with fatigue, pallor, and jaundice. Laboratory tests show hemoglobin of 8.5 g/dL, a reticulocyte count of 6%, and an indirect bilirubin level of 3.5 mg/dL. Which test is most likely to confirm the diagnosis?

Accepted Answer

Direct Coombs test

Answer

Serum ferritin

Answer

Hemoglobin electrophoresis

Answer

Bone marrow biopsy

Question 3

A 65-year-old man presents with cyanosis, confusion, and a pulse oximetry reading of 85% despite receiving supplemental oxygen. What is the most likely cause of his hypoxia?

Accepted Answer

Methemoglobinemia

Answer

Pulmonary embolism

Answer

Congestive heart failure

Answer

Chronic obstructive pulmonary disease

Question 4

A 40-year-old woman with a history of systemic lupus erythematosus (SLE) presents with acute onset of dyspnea and pleuritic chest pain. A chest CT shows multiple bilateral pulmonary emboli. What is the most likely underlying cause?

Accepted Answer

Antiphospholipid syndrome

Answer

Infective endocarditis

Answer

Pulmonary hypertension

Answer

Congestive heart failure

Question 5

A 25-year-old woman presents with episodic hemolysis and hemoglobinuria, particularly at night. What is the most likely diagnosis?

Accepted Answer

Paroxysmal nocturnal hemoglobinuria

Answer

G6PD deficiency

Answer

Hereditary spherocytosis

Answer

Sickle cell disease

Question 6

What is a common early sign of vitamin B12 deficiency?

Accepted Answer

Glossitis

Answer

Jaundice

Answer

Pallor

Answer

Peripheral neuropathy

Question 7

A 65-year-old woman presents with progressive fatigue and abdominal discomfort. Imaging reveals massive splenomegaly. A bone marrow aspirate shows myeloid cells with the Philadelphia chromosome. What is the first-line treatment for this condition?

Accepted Answer

Imatinib

Answer

All-trans retinoic acid

Answer

Hydroxyurea

Answer

Rituximab

Question 8

A 55-year-old man presents with fatigue and shortness of breath. Laboratory results reveal normocytic anemia and increased reticulocytes. Which condition is most consistent with these findings?

Accepted Answer

Hemolytic anemia

Answer

Iron deficiency anemia

Answer

Pernicious anemia

Answer

Aplastic anemia

Question 9

A 32-year-old woman presents with fever, fatigue, jaundice, and anemia. Laboratory results show hemoglobin of 7.5, a high reticulocyte count, and elevated indirect bilirubin. The peripheral smear reveals spherocytes. What is the definitive treatment?

Accepted Answer

Corticosteroids

Answer

Splenectomy

Answer

Blood transfusion

Answer

Immunosuppressive therapy

Question 10

In which condition are multiple lytic lesions typically seen?

Accepted Answer

Multiple myeloma

Answer

Mitral stenosis

Answer

Atherosclerosis

Answer

Osteoporosis

Hematology — MCQs

Hematology — MCQs

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