USMLE Step 1 Hematology Practice Questions

A patient presents with fatigue, pallor, and shortness of breath. Complete blood count (CBC) shows: Hb 8.0 g/dL, Hct 24%, MCV 70 fL, MCH 22 pg, RDW 18%. Serum ferritin is low, TIBC is high. What is the most likely diagnosis?

• (A) Iron deficiency anemia
• (B) Vitamin B12 deficiency anemia
• (C) Folate deficiency anemia
• (D) Anemia of chronic disease

Which coagulation factor deficiency is responsible for Hemophilia A?

• (A) Factor VIII
• (B) Factor IX
• (C) Factor XI
• (D) Factor VII

What is the characteristic peripheral blood smear finding in Vitamin B12 or Folate deficiency anemia?

• (A) Macrocytic red blood cells (high MCV) and hypersegmented neutrophils
• (B) Microcytic, hypochromic red blood cells
• (C) Schistocytes (fragmented RBCs)
• (D) Spherocytes

Which molecule is the primary physiological anticoagulant that inactivates thrombin (Factor IIa) and Factor Xa, especially when potentiated by heparin?

• (A) Antithrombin III (ATIII)
• (B) Protein C
• (C) Protein S
• (D) Tissue factor pathway inhibitor (TFPI)

A peripheral blood smear shows numerous red blood cells that lack central pallor and appear smaller and rounder than normal. Osmotic fragility test is positive. This morphology is characteristic of:

• (A) Hereditary spherocytosis
• (B) Sickle cell anemia
• (C) Thalassemia major
• (D) Iron deficiency anemia

Which hematopoietic growth factor primarily stimulates the production and differentiation of neutrophils?

• (A) Granulocyte colony-stimulating factor (G-CSF)
• (B) Erythropoietin (EPO)
• (C) Thrombopoietin (TPO)
• (D) Interleukin-3 (IL-3)

What is the underlying genetic defect in sickle cell anemia?

• (A) Point mutation in the beta-globin gene (glutamic acid replaced by valine at position 6)
• (B) Deletion of alpha-globin genes
• (C) Defect in spectrin or ankyrin
• (D) Deficiency of Factor VIII

A patient with unexplained thrombosis is found to have a mutation in the Factor V gene (G1691A) that renders Factor Va resistant to inactivation by activated Protein C. What is this condition called?

• (A) Factor V Leiden mutation
• (B) Prothrombin gene mutation (G20210A)
• (C) Antithrombin deficiency
• (D) Protein C deficiency

Which type of leukemia is characterized by the presence of the Philadelphia chromosome (t(9;22) translocation) resulting in the BCR-ABL fusion gene?

• (A) Chronic Myeloid Leukemia (CML)
• (B) Acute Lymphoblastic Leukemia (ALL)
• (C) Acute Myeloid Leukemia (AML)
• (D) Chronic Lymphocytic Leukemia (CLL)

What is the primary function of platelets (thrombocytes)?

• (A) Formation of the primary hemostatic plug at sites of vascular injury
• (B) Transport of oxygen
• (C) Phagocytosis of pathogens
• (D) Production of antibodies

Which vitamin is essential for the gamma-carboxylation of glutamate residues on coagulation Factors II, VII, IX, and X, as well as Proteins C and S, making them functional?

• (A) Vitamin K
• (B) Vitamin B12
• (C) Vitamin C
• (D) Vitamin D

A patient develops severe microcytic anemia after chronic use of non-steroidal anti-inflammatory drugs (NSAIDs). What is the most likely cause?

• (A) Iron deficiency anemia due to chronic gastrointestinal blood loss
• (B) Anemia of chronic disease due to inflammation
• (C) Folate deficiency due to impaired absorption
• (D) Aplastic anemia due to bone marrow suppression

What is the role of von Willebrand factor (vWF) in primary hemostasis?

• (A) Mediates platelet adhesion to exposed subendothelial collagen
• (B) Activates Factor X
• (C) Cross-links fibrin monomers
• (D) Inhibits plasmin

Which type of lymphoma is characterized by the presence of Reed-Sternberg cells on lymph node biopsy?

• (A) Hodgkin lymphoma
• (B) Non-Hodgkin lymphoma (e.g., Diffuse Large B-cell Lymphoma)
• (C) Burkitt lymphoma
• (D) Multiple myeloma

Bernard-Soulier syndrome is a bleeding disorder caused by a deficiency in which platelet receptor, leading to impaired platelet adhesion?

• (A) Glycoprotein Ib (GpIb)
• (B) Glycoprotein IIb/IIIa (GpIIb/IIIa)
• (C) ADP receptor (P2Y12)
• (D) Collagen receptor (GpVI)

What is the main function of plasmin?

• (A) Degradation of fibrin clots (fibrinolysis)
• (B) Activation of coagulation factors
• (C) Aggregation of platelets
• (D) Vasoconstriction

A child presents with petechiae and easy bruising following a viral infection. Platelet count is severely low (e.g., 15,000/µL), but coagulation studies (PT, PTT) are normal. What is the most likely diagnosis?

• (A) Immune Thrombocytopenic Purpura (ITP)
• (B) Hemophilia A
• (C) Disseminated Intravascular Coagulation (DIC)
• (D) Von Willebrand disease

Which laboratory test measures the integrity of the extrinsic and common pathways of coagulation (Factors VII, X, V, II, Fibrinogen)?

• (A) Prothrombin Time (PT) / International Normalized Ratio (INR)
• (B) Activated Partial Thromboplastin Time (aPTT)
• (C) Thrombin Time (TT)
• (D) Bleeding Time

What is the underlying pathophysiology of Thalassemia?

• (A) Reduced or absent synthesis of alpha or beta globin chains of hemoglobin
• (B) Point mutation causing abnormal hemoglobin structure (e.g., HbS)
• (C) Defect in RBC membrane proteins
• (D) Autoimmune destruction of RBCs

Multiple myeloma is a malignancy of which cell type?

• (A) Plasma cells
• (B) Myeloid stem cells
• (C) Lymphoid stem cells
• (D) Mature B lymphocytes

What is the role of Protein C and its cofactor Protein S in the coagulation system?

• (A) Inactivate Factors Va and VIIIa (anticoagulant effect)
• (B) Activate Factor X
• (C) Stabilize the fibrin clot
• (D) Enhance platelet aggregation

A patient taking warfarin develops skin necrosis. This complication is associated with a rapid decrease in the levels of which vitamin K-dependent factor upon initiation of warfarin therapy, especially if the patient has an underlying deficiency?

• (A) Protein C
• (B) Factor VII
• (C) Factor II (Prothrombin)
• (D) Factor X

What is the characteristic morphology of red blood cells seen on a peripheral smear in patients with severe burns or microangiopathic hemolytic anemias (e.g., DIC, TTP, HUS)?

• (A) Schistocytes (fragmented RBCs)
• (B) Spherocytes
• (C) Target cells
• (D) Teardrop cells

Which laboratory test measures the integrity of the intrinsic and common pathways of coagulation (Factors XII, XI, IX, VIII, X, V, II, Fibrinogen)?

• (A) Activated Partial Thromboplastin Time (aPTT)
• (B) Prothrombin Time (PT) / INR
• (C) Fibrinogen level
• (D) D-dimer

What is the function of erythropoietin (EPO)?

• (A) Stimulates red blood cell production in the bone marrow
• (B) Stimulates platelet production
• (C) Stimulates white blood cell production
• (D) Inhibits coagulation

Glanzmann thrombasthenia is a bleeding disorder caused by a deficiency or dysfunction of which platelet receptor, leading to impaired platelet aggregation?

• (A) Glycoprotein IIb/IIIa (GpIIb/IIIa)
• (B) Glycoprotein Ib (GpIb)
• (C) ADP receptor (P2Y12)
• (D) Thromboxane A2 receptor

Aplastic anemia is characterized by pancytopenia (anemia, neutropenia, thrombocytopenia) resulting from:

• (A) Failure or destruction of multipotent hematopoietic stem cells in the bone marrow
• (B) Infiltration of the bone marrow by malignant cells
• (C) Autoimmune destruction of peripheral blood cells
• (D) Deficiency of essential vitamins (B12, folate)

What does the D-dimer test measure?

• (A) Presence of fibrin degradation products, indicating recent or ongoing clot formation and breakdown
• (B) Platelet count
• (C) Factor VIII activity level
• (D) Plasma fibrinogen concentration

In Polycythemia Vera, a myeloproliferative neoplasm, there is autonomous overproduction of which cell line primarily, often associated with a JAK2 mutation?

• (A) Erythrocytes (Red blood cells)
• (B) Neutrophils
• (C) Platelets
• (D) Lymphocytes

What is the role of Tissue Factor (Factor III) in initiating coagulation?

• (A) Activates Factor VII, initiating the extrinsic pathway
• (B) Activates Factor XII, initiating the intrinsic pathway
• (C) Directly converts prothrombin to thrombin
• (D) Binds to platelets to cause aggregation

Hemolytic Uremic Syndrome (HUS), often caused by Shiga toxin-producing E. coli (STEC), is characterized by the triad of:

• (A) Microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury
• (B) Fever, neurologic symptoms, and renal failure
• (C) Pancytopenia, bone marrow failure, and infections
• (D) Bleeding, thrombosis, and elevated liver enzymes

Which term describes red blood cells that are abnormally pale due to reduced hemoglobin content?

• (A) Hypochromic
• (B) Macrocytic
• (C) Poikilocytosis
• (D) Anisocytosis

The direct thrombin inhibitors (e.g., dabigatran, argatroban, bivalirudin) work by:

• (A) Binding directly to the active site of thrombin (Factor IIa), inhibiting its activity
• (B) Inhibiting the synthesis of vitamin K-dependent factors
• (C) Potentiating the activity of antithrombin III
• (D) Inhibiting Factor Xa

What is the primary defect in beta-thalassemia major (Cooley's anemia)?

• (A) Severe deficiency or absence of beta-globin chain synthesis
• (B) Severe deficiency or absence of alpha-globin chain synthesis
• (C) Presence of Hemoglobin S
• (D) Deficiency of Glucose-6-phosphate dehydrogenase (G6PD)

What is the typical pattern of inheritance for Hemophilia A and Hemophilia B?

• (A) X-linked recessive
• (B) Autosomal dominant
• (C) Autosomal recessive
• (D) Mitochondrial

Which condition is characterized by excessive iron absorption and deposition in various organs (liver, pancreas, heart, skin, joints), potentially leading to organ damage?

• (A) Hereditary Hemochromatosis
• (B) Wilson disease
• (C) Alpha-1 antitrypsin deficiency
• (D) Porphyria

Rouleaux formation (stacking of red blood cells like coins) on a peripheral blood smear is typically associated with:

• (A) Increased plasma proteins, especially immunoglobulins (e.g., multiple myeloma)
• (B) Iron deficiency anemia
• (C) Sickle cell trait
• (D) Lead poisoning

What is the main function of tissue plasminogen activator (t-PA)?

• (A) Converts plasminogen to plasmin, initiating fibrinolysis
• (B) Activates Factor VII
• (C) Stabilizes the platelet plug
• (D) Causes vasoconstriction

Disseminated Intravascular Coagulation (DIC) is a complex syndrome characterized by:

• (A) Systemic activation of coagulation leading to widespread microthrombi formation and consumption of platelets/coagulation factors, often followed by bleeding
• (B) Isolated deficiency of Factor VIII
• (C) Autoimmune destruction of platelets only
• (D) Overproduction of red blood cells

A patient presents with fatigue and jaundice. Blood smear shows bite cells and Heinz bodies (precipitated hemoglobin, visible with special stain). Symptoms worsened after taking an antimalarial drug. What enzyme deficiency is likely?

• (A) Glucose-6-phosphate dehydrogenase (G6PD) deficiency
• (B) Pyruvate kinase deficiency
• (C) Hereditary spherocytosis
• (D) Sickle cell anemia