I85PREP
⌘ K
ASCP SH study materials
ASCP SH study resources

ASCP SH practice questions

One question at a time. Build your ASCP SH understanding.

First 50 of 200 questions. Each one lists the choices, the correct answer, and an explanation. The checker at the top of this page saves progress in this browser when it is available.

Continue in the practice tool above to load more questions, 50 at a time.

Question 1Normal Hematopoiesis and Erythrocyte Physiology

During human embryogenesis, which structure is the first to generate blood cells?

  1. Bone marrow
  2. Thymus
  3. Fetal liver
  4. Yolk sac Correct answer.

Explanation

Primitive erythropoiesis begins in the yolk sac blood islands at approximately the third week of gestation. The fetal liver then becomes the dominant site, and the bone marrow takes over near the end of the second trimester.

Question 2Normal Hematopoiesis and Erythrocyte Physiology

Which surface marker is the standard identifier for hematopoietic stem and progenitor cells in bone marrow?

  1. CD3
  2. CD19
  3. CD66b
  4. CD34 Correct answer.

Explanation

CD34 is expressed on hematopoietic stem and progenitor cells and is used clinically to enumerate and harvest them. The most primitive stem cells are additionally CD38-negative and lineage-negative.

Question 3Normal Hematopoiesis and Erythrocyte Physiology

What is the normal circulating lifespan of a human erythrocyte?

  1. 80 days
  2. 120 days Correct answer.
  3. 200 days
  4. 40 days

Explanation

Red cells circulate for roughly 120 days before senescent membrane and metabolic changes lead to clearance by splenic and hepatic macrophages. Markedly shortened survival indicates hemolysis or blood loss.

Question 4Normal Hematopoiesis and Erythrocyte Physiology

Which stain is used to visualize the residual RNA of reticulocytes?

  1. Periodic acid–Schiff
  2. New methylene blue Correct answer.
  3. Prussian blue stain
  4. Wright–Giemsa stain

Explanation

Supravital dyes such as new methylene blue enter unfixed cells and precipitate residual ribosomal RNA as a blue filamentous network. Wright–Giemsa staining after fixation does not demonstrate this RNA, which is why routine smears only show polychromasia.

Question 5Normal Hematopoiesis and Erythrocyte Physiology

Which cells are the principal source of erythropoietin in the adult?

  1. Peritubular cells of the kidney Correct answer.
  2. Bone marrow stromal fibroblast layer
  3. Hepatic Kupffer cells
  4. Splenic red pulp macrophages

Explanation

Erythropoietin is produced by peritubular interstitial fibroblast-like cells of the renal cortex in response to tissue hypoxia, sensed through HIF-2α stabilization. The liver contributes a minor proportion of circulating erythropoietin in adults.

Question 6Normal Hematopoiesis and Erythrocyte Physiology

Which change produces a rightward shift of the oxyhemoglobin dissociation curve?

  1. Decreased PCO2
  2. Decreased temperature
  3. Increased pH
  4. Increased 2,3-BPG Correct answer.

Explanation

A rightward shift indicates reduced oxygen affinity and enhanced tissue unloading. Increased 2,3-BPG, increased temperature, increased PCO2, and decreased pH all stabilize the deoxy (T) conformation and shift the curve right.

Question 7Normal Hematopoiesis and Erythrocyte Physiology

2,3-Bisphosphoglycerate lowers hemoglobin oxygen affinity by binding preferentially to which form?

  1. Methemoglobin
  2. R (oxy) state
  3. Carboxyhemoglobin
  4. T (deoxy) state Correct answer.

Explanation

2,3-BPG sits in the central cavity of the deoxyhemoglobin tetramer, forming salt bridges that stabilize the T state and reduce oxygen affinity. This is the molecular basis of the rightward shift seen with increased 2,3-BPG.

Question 8Normal Hematopoiesis and Erythrocyte Physiology

Hemoglobin A2 is composed of which globin chain pair?

  1. ζ2ε2
  2. α2δ2 Correct answer.
  3. α2γ2
  4. α2β2

Explanation

Hemoglobin A2 contains two alpha and two delta chains and constitutes about 2–3% of adult hemoglobin. Its elevation is a classic feature of beta-thalassemia trait.

Question 9Normal Hematopoiesis and Erythrocyte Physiology

Which hemoglobin predominates in fetal red cells during the third trimester?

  1. HbF Correct answer.
  2. HbA2
  3. HbA
  4. Hb Gower-1

Explanation

By the third trimester, HbF (α2γ2) accounts for the great majority of fetal hemoglobin, with only small amounts of HbA and HbA2. After birth, gamma chain synthesis declines and HbA progressively replaces HbF over the first months of life.

Question 10Normal Hematopoiesis and Erythrocyte Physiology

Which enzyme catalyzes the rate-limiting step of heme synthesis?

  1. Ferrochelatase
  2. PBG deaminase
  3. ALA synthase Correct answer.
  4. ALA dehydratase

Explanation

ALA synthase condenses glycine with succinyl-CoA to form δ-aminolevulinic acid in the mitochondrion, and this is the committed, rate-limiting step. The enzyme is regulated by heme feedback and by iron availability in erythroid precursors.

Question 11Normal Hematopoiesis and Erythrocyte Physiology

Which plasma protein transports iron to erythroid precursors?

  1. Hemosiderin
  2. Ferritin
  3. Transferrin Correct answer.
  4. Hephaestin

Explanation

Transferrin carries ferric iron in plasma and delivers it to erythroid precursors through transferrin receptor 1. Ferritin and hemosiderin are intracellular storage forms rather than circulating carriers.

Question 12Normal Hematopoiesis and Erythrocyte Physiology

Hepcidin lowers plasma iron by which mechanism?

  1. Upregulating transferrin receptor 1
  2. Stimulating heme synthesis
  3. Degrading ferroportin Correct answer.
  4. Increasing duodenal absorption

Explanation

Hepcidin binds ferroportin on enterocytes, macrophages, and hepatocytes, causing its internalization and degradation. Loss of ferroportin blocks cellular iron export, so plasma iron and absorption both fall.

Question 13Normal Hematopoiesis and Erythrocyte Physiology

The hexose monophosphate shunt of the erythrocyte is required chiefly to do what?

  1. Supply NADPH to reduce glutathione Correct answer.
  2. Synthesize membrane spectrin
  3. Generate ATP for cation pumps
  4. Produce 2,3-BPG from 1,3-bisphosphoglycerate

Explanation

The pentose phosphate pathway generates NADPH, which glutathione reductase uses to keep glutathione reduced. Reduced glutathione detoxifies peroxides and protects hemoglobin and membrane lipids from oxidative injury.

Question 14Normal Hematopoiesis and Erythrocyte Physiology

Which pathway generates 2,3-BPG in the mature erythrocyte?

  1. Pentose phosphate pathway
  2. Embden–Meyerhof pathway
  3. Methemoglobin reductase system
  4. Rapoport–Luebering shunt Correct answer.

Explanation

The Rapoport–Luebering shunt diverts 1,3-BPG through bisphosphoglycerate mutase to form 2,3-BPG, bypassing the ATP-generating phosphoglycerate kinase step. This pathway is abundant in red cells and central to oxygen affinity regulation.

Question 15Normal Hematopoiesis and Erythrocyte Physiology

Which protein forms the principal structural network of the red cell membrane skeleton?

  1. Spectrin Correct answer.
  2. Glycophorin A
  3. Band 3
  4. Ankyrin

Explanation

Spectrin dimers self-associate into tetramers and form the flexible submembranous lattice that underlies lipid bilayer stability and deformability. The network is anchored through ankyrin to band 3 and through actin at junctional complexes.

Question 16Normal Hematopoiesis and Erythrocyte Physiology

Mature erythrocytes generate ATP almost exclusively through which process?

  1. Oxidative phosphorylation
  2. The Krebs cycle
  3. Anaerobic glycolysis Correct answer.
  4. β-Oxidation of fatty acids

Explanation

Red cells lack mitochondria and therefore depend on anaerobic glycolysis for ATP production. The ATP generated fuels the Na+/K+ ATPase and calcium pumps that preserve cell volume and deformability.

Question 17Normal Hematopoiesis and Erythrocyte Physiology

Chloride–bicarbonate exchange across the red cell membrane is mediated by which protein?

  1. Glycophorin C
  2. Band 3 (AE1) Correct answer.
  3. Aquaporin-1
  4. Na+/K+ ATPase

Explanation

Band 3, also called the anion exchanger 1, swaps intracellular bicarbonate for plasma chloride, permitting efficient CO2 carriage as bicarbonate. The resulting chloride shift maintains electroneutrality and supports the Bohr effect.

Question 18Normal Hematopoiesis and Erythrocyte Physiology

A sample has a hematocrit of 42% and an RBC count of 4.5 × 10^12/L. What is the MCV?

  1. 78 fL
  2. 93 fL Correct answer.
  3. 115 fL
  4. 105 fL

Explanation

MCV equals hematocrit divided by red cell count: 0.42 L/L ÷ 4.5 × 10^12/L = 93 fL. This falls within the normocytic reference interval of roughly 80–100 fL.

Question 19Normal Hematopoiesis and Erythrocyte Physiology

A sample has a hemoglobin of 15 g/dL and a hematocrit of 45%. What is the MCHC?

  1. 28 g/dL
  2. 36 g/dL
  3. 33 g/dL Correct answer.
  4. 31 g/dL

Explanation

MCHC is hemoglobin divided by hematocrit: 15 ÷ 0.45 = 33.3 g/dL, which rounds to 33 g/dL. Normal MCHC is approximately 32–36 g/dL.

Question 20Normal Hematopoiesis and Erythrocyte Physiology

Which nucleated erythroid stage immediately precedes the reticulocyte?

  1. Pronormoblast
  2. Basophilic normoblast
  3. Orthochromic normoblast Correct answer.
  4. Polychromatophilic normoblast

Explanation

The orthochromic normoblast is the last nucleated stage; it extrudes its pyknotic nucleus and becomes a reticulocyte. The polychromatophilic normoblast is the preceding stage, in which hemoglobin synthesis accelerates.

Question 21Normal Hematopoiesis and Erythrocyte Physiology

In a healthy 40-year-old, what is the approximate cellularity of a bone marrow particle?

  1. 50% Correct answer.
  2. 20%
  3. 35%
  4. 80%

Explanation

Marrow cellularity roughly follows the rule of 100 minus age in years, so about 50–60% hematopoietic cells at age 40, with the remainder being adipose tissue. Cellularity is best judged on an intact particle rather than a dilute aspirate smear.

Question 22Normal Hematopoiesis and Erythrocyte Physiology

Thrombopoietin is produced mainly by which organ?

  1. Kidney
  2. Bone marrow
  3. Liver Correct answer.
  4. Spleen

Explanation

Thrombopoietin is synthesized constitutively by hepatocytes, with the kidney contributing a smaller amount. Circulating levels are regulated largely by receptor-mediated uptake and clearance by platelets and megakaryocytes.

Question 23Normal Hematopoiesis and Erythrocyte Physiology

Which cytokine primarily drives proliferation and maturation of neutrophil precursors?

  1. Erythropoietin
  2. Thrombopoietin
  3. G-CSF Correct answer.
  4. M-CSF

Explanation

Granulocyte colony-stimulating factor acts on committed granulocyte progenitors to increase proliferation, maturation, and release of neutrophils from the marrow. Its clinical use raises neutrophil counts in severe neutropenia.

Question 24Normal Hematopoiesis and Erythrocyte Physiology

Lactoferrin is used as a marker for which granule population in neutrophils?

  1. Tertiary (gelatinase) granules
  2. Azurophilic (primary) granules
  3. Secretory vesicles
  4. Specific (secondary) granules Correct answer.

Explanation

Specific granules contain lactoferrin, lysozyme, and vitamin B12-binding protein and are the defining secondary granule population of neutrophils. Azurophilic granules instead contain myeloperoxidase, elastase, and defensins.

Question 25Normal Hematopoiesis and Erythrocyte Physiology

T lymphocytes complete antigen receptor rearrangement and maturation in which organ?

  1. Thymus Correct answer.
  2. Bone marrow
  3. Lymph node
  4. Spleen

Explanation

T-cell progenitors arise in the bone marrow but migrate to the thymus, where they undergo T-cell receptor gene rearrangement and positive and negative selection. B cells, in contrast, complete maturation in the bone marrow before migrating to peripheral lymphoid tissue.

Question 26Normal Hematopoiesis and Erythrocyte Physiology

Erythropoietin that supports red cell production in a healthy adult is synthesized chiefly by which cells?

  1. Cardiac pacemaker cells
  2. Pancreatic acinar cells
  3. Renal peritubular cells Correct answer.
  4. Hepatic parenchymal cells

Explanation

In adults, erythropoietin is produced mainly by peritubular interstitial cells of the renal cortex in response to tissue hypoxia. The liver is the principal source during fetal life but contributes little in the adult.

Question 27Normal Hematopoiesis and Erythrocyte Physiology

Reticulocytes are highlighted on a blood smear by supravital staining of residual RNA with which dye?

  1. Wright stain
  2. New methylene blue Correct answer.
  3. Prussian blue
  4. Periodic acid-Schiff

Explanation

New methylene blue is a supravital dye that precipitates residual RNA in reticulocytes, producing a visible filamentous network. Wright stain is applied after fixation and does not demonstrate reticular RNA.

Question 28Normal Hematopoiesis and Erythrocyte Physiology

What is the average circulating lifespan of a normal human red blood cell?

  1. 20 days
  2. 180 days
  3. 60 days
  4. 120 days Correct answer.

Explanation

Normal red cells circulate for about 120 days before senescent membranes are recognized and the cells are removed by macrophages, chiefly in the spleen. This lifespan balances daily erythropoiesis with destruction.

Question 29Normal Hematopoiesis and Erythrocyte Physiology

Which cell-surface marker is most characteristic of human hematopoietic stem and progenitor cells?

  1. CD3
  2. CD19
  3. CD45RA
  4. CD34 Correct answer.

Explanation

CD34 is expressed on hematopoietic stem and progenitor cells and is widely used to identify and enumerate them. CD3 marks T cells, CD19 marks B cells, and CD45RA marks naive T cells.

Question 30Normal Hematopoiesis and Erythrocyte Physiology

A bone marrow aspirate shows a nucleated red cell with deeply basophilic cytoplasm, a round nucleus, and visible nucleoli. This cell is best classified as which stage?

  1. Basophilic normoblast Correct answer.
  2. Orthochromic normoblast
  3. Polychromatophilic normoblast
  4. Reticulocyte

Explanation

Basophilic normoblasts have deeply basophilic cytoplasm and nuclei with visible nucleoli early in erythroid maturation. As hemoglobin accumulates, the cytoplasm becomes polychromatophilic and the nucleus condenses.

Question 31Normal Hematopoiesis and Erythrocyte Physiology

Adult hemoglobin A is composed of which globin chain pair arrangement?

  1. Two beta and two delta chains
  2. Two alpha and two delta chains
  3. Four beta chains
  4. Two alpha and two beta chains Correct answer.

Explanation

Hemoglobin A, the predominant adult hemoglobin, is a tetramer of two alpha and two beta globin chains. Hemoglobin A2 contains two alpha and two delta chains, and hemoglobin H is a beta-chain tetramer.

Question 32Normal Hematopoiesis and Erythrocyte Physiology

Which protein is the principal soluble iron-storage protein within cells?

  1. Ferritin Correct answer.
  2. Transferrin
  3. Ceruloplasmin
  4. Hemosiderin

Explanation

Ferritin is a soluble, hollow protein shell that stores iron in a nontoxic form and releases it as needed. Hemosiderin is an insoluble aggregate of partially degraded ferritin and represents a secondary storage form.

Question 33Normal Hematopoiesis and Erythrocyte Physiology

Dietary vitamin B12 is absorbed in the terminal ileum after binding to which protein?

  1. Hepatic haptoglobin
  2. Plasma transferrin
  3. Intrinsic factor Correct answer.
  4. Duodenal ferroportin

Explanation

Gastric parietal cells secrete intrinsic factor, which binds vitamin B12 and carries it to cubilin receptors in the terminal ileum. Without intrinsic factor, B12 absorption is severely impaired.

Question 34Normal Hematopoiesis and Erythrocyte Physiology

Which process allows a single megakaryocyte to generate many platelets?

  1. Endomitosis Correct answer.
  2. Fusion with macrophages
  3. Apoptosis of the nucleus
  4. Asymmetric mitotic division

Explanation

Megakaryocytes undergo endomitosis, replicating DNA without completing cell division, which produces a large polyploid cell. The mature cell extends proplatelets that fragment into platelets.

Question 35Normal Hematopoiesis and Erythrocyte Physiology

A patient with chronic kidney disease has anemia with a low reticulocyte count. Which mechanism best explains the anemia?

  1. Inadequate erythropoietin production Correct answer.
  2. Decreased iron absorption from hepcidin deficiency
  3. Impaired globin chain synthesis
  4. Increased red cell destruction by splenic macrophages

Explanation

The kidneys produce most adult erythropoietin, so chronic kidney disease can reduce erythropoietin output and impair erythroid proliferation. The result is a hypoproliferative anemia with an inappropriately low reticulocyte response.

Question 36Normal Hematopoiesis and Erythrocyte Physiology

Which form of iron in hemoglobin binds oxygen reversibly?

  1. Elemental (Fe0)
  2. Ferrous (Fe2+) Correct answer.
  3. Ferric (Fe3+)
  4. Ferryl (Fe4+)

Explanation

Hemoglobin binds oxygen only when the heme iron is in the ferrous, Fe2+, state. Oxidation to ferric iron forms methemoglobin, which cannot bind oxygen reversibly.

Question 37Normal Hematopoiesis and Erythrocyte Physiology

Glycophorins on the red cell membrane carry which blood group antigens?

  1. ABO antigens
  2. Kell antigens
  3. MNS antigens Correct answer.
  4. Rh antigens

Explanation

Glycophorin A carries M and N antigens, and glycophorin B carries S and s antigens of the MNS blood group system. ABO antigens are carbohydrate structures, whereas Rh and Kell antigens reside on distinct membrane proteins.

Question 38Normal Hematopoiesis and Erythrocyte Physiology

Which transcription factor is a master regulator of erythroid differentiation and binds GATA motifs in globin gene regulatory regions?

  1. PAX5 transcription factor
  2. MYB transcription factor
  3. GATA1 protein Correct answer.
  4. PU.1 transcription factor

Explanation

GATA1 is essential for erythroid lineage commitment and maturation and activates many erythroid-specific genes, including globin genes. PU.1 drives myeloid and B-lymphoid programs, while PAX5 is a B-cell factor.

Question 39Normal Hematopoiesis and Erythrocyte Physiology

Which enzyme reduces methemoglobin back to functional hemoglobin in red cells?

  1. Glucose-6-phosphate dehydrogenase
  2. Cytochrome b5 reductase Correct answer.
  3. Methemoglobin peroxidase
  4. Pyruvate kinase

Explanation

NADH-cytochrome b5 reductase transfers electrons from NADH to cytochrome b5, which reduces ferric heme iron back to ferrous iron. This pathway keeps methemoglobin levels low in normal red cells.

Question 40Normal Hematopoiesis and Erythrocyte Physiology

In the red cell membrane skeleton, ankyrin connects spectrin to which integral membrane protein?

  1. CD47
  2. RhAG
  3. Band 3 Correct answer.
  4. Glycophorin A

Explanation

Ankyrin binds the spectrin tetramer and links it to the cytoplasmic domain of band 3, anchoring the membrane skeleton to the lipid bilayer. This connection helps maintain red cell shape and deformability.

Question 41Erythrocyte Disorders and Anemias

Which laboratory pattern is most characteristic of iron deficiency anemia?

  1. Low ferritin with low TIBC
  2. Normal ferritin with low TIBC
  3. Low ferritin with high TIBC Correct answer.
  4. High ferritin with normal TIBC

Explanation

Iron deficiency depletes storage iron, so serum ferritin falls and transferrin, reflected by TIBC, rises; transferrin saturation is low. A low ferritin with a low TIBC is more typical of anemia of chronic disease.

Question 42Erythrocyte Disorders and Anemias

Which peripheral blood finding is most characteristic of megaloblastic anemia?

  1. Hypersegmented neutrophils Correct answer.
  2. Schistocytes
  3. Basophilic stippling
  4. Howell-Jolly bodies

Explanation

Megaloblastic anemia results from impaired DNA synthesis, producing nuclear-cytoplasmic asynchrony in dividing cells. Neutrophils with six or more lobes, called hypersegmentation, are a hallmark.

Question 43Erythrocyte Disorders and Anemias

Which hemoglobin is responsible for sickle cell anemia?

  1. Hemoglobin C
  2. Hemoglobin F
  3. Hemoglobin H
  4. Hemoglobin S Correct answer.

Explanation

Sickle cell anemia is caused by homozygosity for a beta-globin mutation that produces hemoglobin S. Deoxygenated HbS polymerizes and distorts red cells into sickle forms.

Question 44Erythrocyte Disorders and Anemias

A patient with warm autoimmune hemolytic anemia has a positive direct antiglobulin test. What does this test primarily detect?

  1. RBC-bound immunoglobulin Correct answer.
  2. Plasma free hemoglobin
  3. Red cell membrane proteins
  4. Complement fragments in plasma

Explanation

The direct antiglobulin test detects immunoglobulin and/or complement bound to the red cell surface. A positive result supports an immune cause of hemolysis.

Question 45Erythrocyte Disorders and Anemias

Which red cell morphology is most typical of microangiopathic hemolytic anemia?

  1. Spherocytes
  2. Target cells
  3. Schistocytes Correct answer.
  4. Stomatocytes

Explanation

Microangiopathic hemolysis occurs when red cells are fragmented by fibrin strands or shear stress in small vessels. Schistocytes are the resulting fragmented forms.

Question 46Erythrocyte Disorders and Anemias

Aplastic anemia typically presents with which peripheral blood pattern?

  1. Pancytopenia with reticulocytopenia Correct answer.
  2. Isolated thrombocytopenia with normal hemoglobin
  3. Pancytopenia with reticulocytosis
  4. Isolated anemia with normal platelets and leukocytes

Explanation

Aplastic anemia is bone marrow failure that reduces all hematopoietic lineages, producing pancytopenia. The reticulocyte count is low because the marrow cannot mount a compensatory response.

Question 47Erythrocyte Disorders and Anemias

Erythropoietin, the principal regulator of red cell production, is produced mainly by which organ?

  1. Kidney Correct answer.
  2. Bone marrow
  3. Spleen
  4. Liver

Explanation

The kidney produces most erythropoietin in adults in response to tissue hypoxia. Renal failure therefore commonly causes anemia through insufficient erythropoietin.

Question 48Erythrocyte Disorders and Anemias

Howell-Jolly bodies in peripheral blood most commonly indicate which condition?

  1. Splenic hypofunction Correct answer.
  2. Iron deficiency
  3. Megaloblastic anemia
  4. Thalassemia minor

Explanation

Howell-Jolly bodies are nuclear remnants that normally are removed by the spleen. Their presence suggests splenic hypofunction or prior splenectomy.

Question 49Erythrocyte Disorders and Anemias

A patient with rheumatoid arthritis has a normocytic anemia. Which iron profile is most consistent with anemia of chronic disease?

  1. Low iron, low TIBC, high ferritin Correct answer.
  2. Normal iron, normal TIBC, low ferritin
  3. High iron, high TIBC, low ferritin
  4. Low iron, high TIBC, low ferritin

Explanation

Inflammation raises hepcidin, which traps iron in macrophages and reduces intestinal iron absorption while ferritin rises as an acute-phase reactant. Serum iron and TIBC are therefore low, with normal or high ferritin.

Question 50Erythrocyte Disorders and Anemias

Ring sideroblasts in the bone marrow are most characteristic of which disorder?

  1. Immune thrombocytopenia
  2. Hereditary spherocytosis
  3. Sideroblastic anemia Correct answer.
  4. Megaloblastic anemia

Explanation

Ring sideroblasts are erythroid precursors with iron-loaded mitochondria forming a perinuclear ring. They define sideroblastic anemia, which can be caused by lead, alcohol, isoniazid, or ALAS2 mutations.