Hematopathology: Erythrocyte Lineage Disorders

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Questions and Answers

Which of the following best describes the role of hematopoietic stem cells?

  • Mature blood cells ready for circulation.
  • Specialized cells that directly combat infections.
  • Precursors to erythrocytes that enhance the blood's oxygen carrying capacity.
  • Undifferentiated cells capable of differentiating into various blood cell lineages. (correct)

A complete blood count (CBC) provides information about the cellular components of blood. Which of the following is NOT a direct measurement reported in a standard CBC?

  • Red blood cell (RBC) count.
  • Hematocrit (Hct).
  • Erythrocyte sedimentation rate (ESR). (correct)
  • Mean corpuscular volume (MCV).

The peripheral blood smear is useful in identifying cellular abnormalities. What is the primary purpose of examining a peripheral blood smear?

  • To measure the oxygen-carrying capacity of red blood cells.
  • To quantify the levels of various clotting factors.
  • To assess the size, shape, and color of blood cells. (correct)
  • To determine the exact number of each type of blood cell.

A reticulocyte count can help differentiate between different types of anemia. An elevated reticulocyte count suggests:

<p>Increased red blood cell destruction or blood loss. (D)</p> Signup and view all the answers

Which of the following laboratory tests is most useful in assessing polycythemia?

<p>Erythropoietin (EPO) level. (A)</p> Signup and view all the answers

Hyper-proliferation, hypo-proliferation, and dilution are terms that describe hematologic diseases. Which condition is most closely associated with hypo-proliferation?

<p>Aplastic anemia. (A)</p> Signup and view all the answers

A patient's red blood cell indices show microcytic/hypochromic cells. Which of the following conditions is most likely?

<p>Iron deficiency anemia. (D)</p> Signup and view all the answers

In the classification of hematopathology based on lineages, which category includes disorders affecting the cells responsible for oxygen transport?

<p>Erythrocyte disorders. (B)</p> Signup and view all the answers

During hematopoiesis, a myeloid stem cell can differentiate into several types of blood cells. Which of the following is a product of myeloid stem cell differentiation?

<p>Monocyte. (A)</p> Signup and view all the answers

What is the primary function of erythropoietin (EPO) in the context of hematopoiesis?

<p>Stimulating the production of red blood cells. (D)</p> Signup and view all the answers

Which of the following etiologies is associated with decreased red blood cell production?

<p>Iron deficiency. (D)</p> Signup and view all the answers

Which of the following conditions is an example of anemia due to blood loss?

<p>Postpartum hemorrhage. (C)</p> Signup and view all the answers

Which of the following enzyme defects leads to disorders of increased red blood cell destruction?

<p>Glucose-6-Phosphate Dehydrogenase Deficiency (D)</p> Signup and view all the answers

What is the underlying mechanism of anemia of chronic disease (ACD)?

<p>Impaired erythropoiesis due to inflammatory cytokines. (B)</p> Signup and view all the answers

How does hepcidin contribute to the development of anemia of chronic disease?

<p>Inhibits the release of iron from macrophages. (D)</p> Signup and view all the answers

What characterizes 'relative' polycythemia?

<p>Reduction of plasma volume leading to hemoconcentration. (A)</p> Signup and view all the answers

Which of the following conditions is considered a 'secondary absolute cause' of polycythemia?

<p>Chronic lung disease. (D)</p> Signup and view all the answers

In the context of absolute polycythemia, what is the primary difference between primary and secondary causes?

<p>Primary causes involve abnormal proliferation of myeloid stem cells, while secondary causes are due to elevated EPO levels. (B)</p> Signup and view all the answers

If a patient has a normal hemoglobin level but exhibits symptoms of anemia, which RBC index would be most helpful in further evaluating the type of anemia?

<p>MCV. (A)</p> Signup and view all the answers

In evaluating a CBC, which component is essential for assessing a patient for infection?

<p>White blood cell count with differential. (D)</p> Signup and view all the answers

What is the primary utility of examining a peripheral blood smear in the context of hematological disorders?

<p>To assess the morphology and structural abnormalities of blood cells. (C)</p> Signup and view all the answers

An increased reticulocyte count is associated with increased red blood cell production, and with certain types of anemia. Which of the following conditions would most likely present with an elevated reticulocyte count?

<p>Iron deficiency anemia after iron supplementation. (C)</p> Signup and view all the answers

In the context of iron studies, what does the serum ferritin level primarily indicate?

<p>The body's iron stores. (A)</p> Signup and view all the answers

In iron studies, which of the following results indicates iron deficiency anemia?

<p>Low serum iron, low ferritin, high TIBC. (A)</p> Signup and view all the answers

In hemoglobin electrophoresis, which hemoglobin variant migrates to the greatest extent from cathode to anode?

<p>HbA. (B)</p> Signup and view all the answers

What characteristic of red blood cells defines hypochromic anemia?

<p>Reduced concentration of hemoglobin. (A)</p> Signup and view all the answers

What is a typical finding in the peripheral blood smear of a patient with Glucose-6-Phosphate Dehydrogenase Deficiency?

<p>Bite cells. (A)</p> Signup and view all the answers

What laboratory finding is expected in a patient with macrocytic anemia due to Vitamin B12 deficiency?

<p>Increased MCV, decreased reticulocyte count (A)</p> Signup and view all the answers

Which of the following anemias is usually classified as normocytic and normochromic?

<p>Sickle cell anemia. (A)</p> Signup and view all the answers

What is the main reason for anemia in a patient with chronic kidney disease?

<p>Decreased erythropoietin production. (C)</p> Signup and view all the answers

During an initial evaluation of anemia, after taking a history and performing a physical exam, which of the following is the next most appropriate step?

<p>CBC with interpretation of indices. (B)</p> Signup and view all the answers

What is the role of physical examination in determining the causes for anemia?

<p>To get an idea of possible underlying systemic issues that result in anemia. (C)</p> Signup and view all the answers

After initial assessment with a CBC, which lab test helps determine if anemia is caused by increased destruction of red blood cells?

<p>Reticulocyte Count (B)</p> Signup and view all the answers

When evaluating macrocytic anemia, why is it important to assess both Vitamin B12 and folate levels?

<p>Because deficiencies in either can result in macrocytic anemia. (B)</p> Signup and view all the answers

What is the clinical implication of a bone marrow aspiration in the workup of anemia?

<p>To directly observe the cell morphology to identify and classify cell issues. (A)</p> Signup and view all the answers

Which of the following accurately describes the role and production of myeloid and lymphoid stem cells?

<p>Myeloid stem cells differentiate into erythrocytes, granulocytes, monocytes, and platelets, while lymphoid stem cells give rise to lymphocytes. (C)</p> Signup and view all the answers

When analyzing a CBC, which diagnostic insight can be derived from evaluating the red blood cell (RBC) indices?

<p>RBC indices can help classify anemias based on cell size and hemoglobin concentration, with the goal of guiding specific diagnostic approaches. (A)</p> Signup and view all the answers

In the evaluation of anemia, what are the distinct characteristics of sideroblastic anemia?

<p>High serum Iron, with high serum Ferritin, with low TIBC. (C)</p> Signup and view all the answers

When observing a peripheral blood smear, which abnormal finding suggests hereditary spherocytosis?

<p>Spherocytes. (C)</p> Signup and view all the answers

Flashcards

Hematopathology Organization

The overall structure of hematopathology including erythrocyte lineage disorders.

Complete Blood Count (CBC)

Complete blood count-evaluates cells circulating in blood

What is complete blood count(CBC)?

A blood test evaluating cells that circulate in blood.

What are CBC components?

White blood cell count, red blood cell count, hemoglobin, hematocrit, RBC indices, platelet count.

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H/H

Hemoglobin (Hgb or Hb); Hematocrit (Hct)

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What are RBC indices?

Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), Mean Corpuscular Hemoglobin Concentration (MCHC), Red Cell Distribution Width (RDW)

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Peripheral Blood Smear

Evaluates the morphology of blood cells.

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What are Reticulocytes?

Red blood cell-large, immature

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High Reticulocyte Count

Increased reticulocyte counts indicates blood loss or hemolytic anemia

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Ferritin

Protein that stores iron.

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Transferrin

Protein that transports iron in the blood.

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TIBC

Total Iron Binding Capacity; measures how much iron can bind to transferrin.

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What is Ferritin?

The protein that stores iron.

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Hypochromic

Less hemoglobin than the normal amount.

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Microcytic

Smaller than usual cells (MCV < 80 fL).

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Normochromic

Normal hemoglobin concentration.

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Normocytic

Cells are normal-sized (MCV 80-100 fL).

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Macrocytic

Cells are larger than usual (MCV >100 fL).

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Study Notes

  • Hematologic Concepts 1, Winter 2025
  • Presenter: Jeanette Rodríguez, D.O., Assistant Professor of Family Medicine at Nova Southeastern University

Student Learning Objectives

  • Describe the organization of hematopathology and identify erythrocyte lineage disorders
  • Briefly discuss the role of stem cells in hematopoietic and lymphoreticular diseases
  • List the components and clinical applications of the complete blood count (CBC)
  • Discuss the value of the peripheral blood smear in diagnosing hematologic and other disorders
  • Define reticulocyte and discuss the clinical implication of the reticulocyte count
  • Identify lab tests used to assess anemia and polycythemia
  • Define hematologic diseases characterized by hyper-proliferation, hypo-proliferation, and dilution
  • Describe diseases associated with normocytic/normochromic, microcytic/hypochromic, and macrocytic RBC indices

Classification of Hematopathology Based on Lineages

  • Hematopathology includes erythrocyte disorders, WBC disorders, plasma cell disorders and platelet disorders
  • This lecture focuses on erythrocyte disorders

Hematopoiesis: Blood Cell Differentiation and Lineages

  • Blood cell differentiation and lineages originate from hematopoietic stem cells
  • These differentiate into myeloid and lymphoid stem cells
  • Myeloid stem cells differentiate into: Erythrocytes, Megakaryoblasts, Monoblasts
  • Lymphoid stem cells differentiate into: Lymphoblasts

Hematopathology: Classification of Disorders of RBC

  • Classification of disorders of red blood cells includes anemia (too few cells) and erythrocytosis/polycythemia (too many cells)

Anemia: Etiology

  • Anemia is caused by: blood loss (hemorrhage), decreased production, and increased destruction

Anemia: Blood Loss

  • Acute etiologies include acute trauma, acute hemorrhage including postpartum hemorrhage, GYN, GI, urologic etiologies
  • Chronic etiologies include GI lesions, malignancies, other causes such as angiodysplasia, hemorrhoids, colon cancer, bleeding peptic ulcer
  • Chronic etiologies also include GYN lesions, malignancies, other causes such as menorrhagia, fibroids, and adenomyosis

Anemia: Disorders of Increased Destruction

  • Enzyme defects: Glucose-6-Phosphate Dehydrogenase Deficiency, Pyruvate Kinase Deficiency
  • Disorders of Hemoglobin Synthesis: Sickle Cell Anemia, Thalassemia
  • Membrane Defects: Hereditary Spherocytosis, Elliptocytosis
  • Acquired disorders include Paroxysmal Nocturnal Hemoglobinuria
  • Immune Mediated disorders: Rh disease of the newborn, Systemic Lupus Erythematosus
  • Infections: Malaria and other parasitic infections

Anemia: Disorders of Decreased Production

  • Lack of raw materials like iron deficiency anemia, anemia of chronic disease, folate deficiency anemia, and vitamin B12 (cobalamin) deficiency anemia can cause decreased production
  • Problems with bone marrow like myelophthisic anemia (marrow infiltration), aplastic anemia, and pure red cell dysplasia
  • Other causes include chronic inflammation and chronic diseases like diabetes mellitus, rheumatologic conditions, hypertension, coronary artery disease, and congestive heart failure

Anemia of Chronic Disease (ACD) / Anemia of Inflammation (AI)/ Anemia of Chronic Inflammation (ACI)

  • Secondary iron metabolism issues are caused by inflammation
  • Hepcidin regulates iron metabolism and is an inhibitor

Polycythemia (Erythrocytosis): Etiology

  • Polycythemia (Erythrocytosis) etiologies include relative and absolute causes

Polycythemia (Erythrocytosis): Relative Causes

  • Reduction of plasma volume leads to hemoconcentration
  • Examples include vomiting, diarrhea and polyuria

Polycythemia (Erythrocytosis): Absolute Causes

  • Primary causes: abnormal proliferation of myeloid stem cells with normal or low EPO levels, Ex: Polycythemia Vera
  • Secondary causes: Proliferation of myeloid stem cells in the setting of elevated EPO levels

What are some causes of elevated EPO (i.e. secondary absolute causes)?

  • Chronic lung disease
  • Cyanotic heart disease
  • High-altitude living
  • Intake of EPO (athletes)
  • EPO secreting tumors (renal cell carcinoma, hepatoma, cerebellar hemangioblastoma)

Into to the World of Lab Tests

  • Complete Blood Count is a blood test performed with peripheral blood drawn that evaluates cells that circulate in the blood

Complete Blood Count (CBC)

  • Components: White Blood Cell (WBC) count with or without a differential; Red Blood Cell (RBC) count, Hemoglobin (Hgb or Hb) and Hematocrit (Hct), RBC indices; Platelet count with or without Mean Platelet Volume (MPV) and/or Platelet Distribution Width (PDW)
  • Hgb/Hct are sometimes referred to together as H/H

Complete Blood Count (CBC): RBC Indices

  • RBC Count: # of red blood cells per cc of blood
  • Hemoglobin: Measure of amount of O2 carrying protein in RBCs
  • Hematocrit (HCT): Measures volume percentage of RBC in blood
  • MCH: Measure of the amount of Hgb per cell
  • MCHC: Measure of the concentration of Hgb in each RBC
  • MCV: Measure of RBC size
  • MCHC descriptors: normochromic, hypochromic, hyperchromic
  • MCV descriptors: normocytic, microcytic, macrocytic

Complete Blood Count (CBC) usage:

  • Evaluate infection, anemia, malignancy, heritable conditions, conditions of altered bone marrow production of cells

Peripheral Smear (normal)

  • Evaluates morphology

Peripheral Smear Findings

  • Peripheral Smear: Sickle cell shows sickle cells
  • Peripheral Smear: G6PD Deficiency shows Heinz bodies, bite cells

Reticulocytes

  • Reticulocytes = large immature RBC
  • Reticulocyte counts indicate significant blood loss anemia or hemolytic anemia

Iron Studies

  • Iron Panel Tests: Ferritin, Transferrin, TIBC and Iron

Iron Studies: Definitions

  • Ferritin: Protein that stores iron
  • Transferrin: Protein that transports iron in the blood
  • TIBC: Total Iron Binding Capacity; how much Fe can be bound to transferrin

Iron Studies: Disease

  • Iron Deficiency: ↓ Serum Iron, ↓ Serum Ferritin, ↑ TIBC, ↓ Iron Saturation %
  • Anemia of Chronic Disease: ↓ Serum Iron, NL or ↑ Serum Ferritin, ↓ or NL TIBC, NL or ↓ Iron Saturation %
  • Thalassemia: ↑ Serum Iron, ↑ Serum Ferritin, ↓ TIBC, ↑ Iron Saturation %
  • Sideroblastic: ↑ Serum Iron, ↑ Serum Ferritin, ↓ TIBC, ↑ Iron Saturation %
  • Transferrin is reflected by TIBC in labs

Hemoglobin Electrophoresis

  • Separates hemoglobins based on charge from cathode to anode on a electrophoretic gel
  • Hemoglobin migrates from the negatively charged cathode to the positively charged anode
  • HbA migrates the farthest, followed by HBF, HbS, and HbC.
  • Missense mutations in HbS and HBC replace glutamic acid with valine (neutral) and lysine (making HbC and HbS more positively charged than НЬА).

Anemia Characterization Based on Morphology

  • Based on RBC indices

Hypochromic and Microcytic

  • Hypochromic: less than normal amount of hemoglobin; Look at MCHC
  • Microcytic: cells are smaller than usual, look at MCV (MCV Range: < 80 fL)
  • Hemoglobin problem
  • Common Etiologies: Iron Deficiency Anemia and Thalassemia

Normocytic Normochromic

  • Normochromic: normal hemoglobin concentration. Look at MCHC (MCHC Range: 30-34)
  • Normocytic: cells are normal sized. Look at MCV (MCV Range: 80-100 fL)
  • Not enough cells
  • Common Etiologies: Hereditary Spherocytosis, Sickle Cell Disease, Acute blood loss, Myelofibrosis, Anemia of chronic disease (*usually), Renal disease

Macrocytic

  • Macrocytic: cells are larger than usual. Look at MCV (MCV range: >100 fL)
  • DNA problem
  • Common Etiologies: B12 Deficiency Anemia such as Pernicious anemia, strict vegetarians and Folate Deficiency Anemia

Anemia Comparison Chart

  • Microcytic anemia results from a hemoglobin problem and has MCV < 80 fL
  • Normocytic anemia results from not enough cells having MCV 80-100 fL
  • Macrocytic anemia results from defective DNA Synthesis, and has MCV >100 fL

Initial Evaluation of Anemia

  • History
  • Physical Exam
  • CBC with interpretation of indices
  • Reticulocyte count

Additional Anemia Work-up (as needed)

  • Blood smear
  • Iron/TIBC
  • B12 level
  • Folic acid level
  • Bilirubin
  • Hemoglobin electrophoresis
  • Osmotic fragility test
  • Bone marrow aspiration

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