Anemia and Red Blood Cell Characteristics
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Questions and Answers

What does the term 'anisocytosis' refer to regarding red blood cells?

  • The process of red blood cell production.
  • The variation in the size of red blood cells. (correct)
  • The presence of uniform, circular red blood cells.
  • The variation in the color of red blood cells.

    • Which of the following best defines macrocytosis?

  • Red blood cells that have an irregular shape.
  • Red blood cells that are larger than normal. (correct)
  • Red blood cells that have a normal size.
  • Red blood cells that are smaller than normal.

    • A patient is diagnosed with anemia. Which of the following is a possible characteristic of their red blood cell count?

  • A lower than normal red blood cell count. (correct)
  • A higher than normal red blood cell count.
  • A normal red blood cell count for their age and gender.
  • A red blood cell count that fluctuates greatly and inconsistently.

    • Which factor can cause an increase in the red blood cell count above normal physiological range?

    <p>The body's requirements for greater oxygen-carrying capacity, e.g. high altitudes.</p> Signup and view all the answers

    The Mean Corpuscular Volume (MCV) is a measure of what property of red blood cells?

    <p>The average size or volume of red blood cells.</p> Signup and view all the answers

    What is the primary function of hemoglobin in the blood?

    <p>To transport oxygen and carbon dioxide</p> Signup and view all the answers

    In which situation would you expect an increased reticulocyte count?

    <p>Severe bleeding or hemolysis</p> Signup and view all the answers

    What does an increased mean corpuscular volume (MCV) indicate about red blood cells?

    <p>They are abnormally large</p> Signup and view all the answers

    What measurement provides an indirect assessment of the total red blood cell (RBC) number and volume?

    <p>Hematocrit</p> Signup and view all the answers

    What condition is associated with a normal to low reticulocyte count?

    <p>Aplastic anemia</p> Signup and view all the answers

    Which of the following factors can cause hemodilution?

    <p>Infusion of fluids</p> Signup and view all the answers

    How is the mean corpuscular hemoglobin (MCH) calculated?

    <p>Total hemoglobin concentration divided by RBC count</p> Signup and view all the answers

    What is the significance of the red blood cell distribution width (RDW)?

    <p>It indicates the variation in RBC size</p> Signup and view all the answers

    Which of the following anemia types is typically caused by a production defect and characterized by a normal to low reticulocyte count?

    <p>Iron deficiency anemia</p> Signup and view all the answers

    What would be the expected hematocrit value for a male adult?

    <p>4.7-6.1 %</p> Signup and view all the answers

    How does pregnancy typically affect hemoglobin levels?

    <p>Levels slightly decrease due to hemodilution</p> Signup and view all the answers

    Which factor is commonly associated with increased hemoglobin levels?

    <p>Smoking habits</p> Signup and view all the answers

    What relation does the hematocrit have to hemoglobin concentration under normal conditions?

    <p>Hematocrit is approximately three times hemoglobin concentration</p> Signup and view all the answers

    Which condition is characterized by the presence of irreversibly sickled cells and chronic hemolysis?

    <p>Sickle Cell Anemia</p> Signup and view all the answers

    In which condition would you expect to see Howell-Jolly bodies?

    <p>Sickle Cell Disease</p> Signup and view all the answers

    What results from imbalanced synthesis of globin chains in thalassemia?

    <p>Decreased red cell production and life span</p> Signup and view all the answers

    What is a common complication of sickle cell crises?

    <p>Severe pain due to vascular occlusion</p> Signup and view all the answers

    Which gene mutation is associated with beta-thalassemia?

    <p>Chromosome 11</p> Signup and view all the answers

    Which of the following is a key morphological finding in Beta Thalassemia Major?

    <p>Marked anisocytosis and poikilocytosis</p> Signup and view all the answers

    Which condition is primarily associated with an increase in the risk of sepsis due to splenic autoinfarction?

    <p>Sickle cell disease</p> Signup and view all the answers

    How is alpha-thalassemia characterized at a genetic level?

    <p>Deletion of alpha globin genes</p> Signup and view all the answers

    What is a common hematological manifestation of hereditary spherocytosis?

    <p>Increased reticulocyte count</p> Signup and view all the answers

    Which population group is particularly known for carrying the HbS gene?

    <p>West Africans</p> Signup and view all the answers

    Which clinical feature is associated with Beta-Thalassemia Major?

    <p>Growth retardation due to severe anemia</p> Signup and view all the answers

    What is the primary cause of sideroblastic anemia?

    <p>Abnormal erythropoiesis during heme production</p> Signup and view all the answers

    Which enzyme is NOT involved in the Shemin pathway for heme synthesis?

    <p>Ferritin</p> Signup and view all the answers

    What is the primary consequence of reduced alpha chain synthesis in alpha thalassemia?

    <p>Accumulation of beta-globin chains leading to damage</p> Signup and view all the answers

    What distinguishes sideroblastic anemia from iron deficiency anemia?

    <p>Increased iron stores</p> Signup and view all the answers

    What characteristic change occurs in the spleen due to sickle cell disease?

    <p>Infarction leading to progressive shrinkage</p> Signup and view all the answers

    Which condition is a major cause of anemia of chronic disease?

    <p>Rheumatoid arthritis</p> Signup and view all the answers

    Which symptom is commonly associated with sideroblastic anemia?

    <p>Bronze-colored skin</p> Signup and view all the answers

    What is a characteristic finding in patients with anemia of chronic disease?

    <p>Low serum iron and decreased total iron-binding capacity</p> Signup and view all the answers

    Which type of anemia is characterized by pancytopenia?

    <p>Aplastic anemia</p> Signup and view all the answers

    In what scenario would polycythemia be considered absolute?

    <p>Intrinsic abnormality of hematopoietic precursors</p> Signup and view all the answers

    Pure red cell aplasia is primarily associated with suppression of what?

    <p>Erythroid progenitors</p> Signup and view all the answers

    Which form of anemia is characterized by life-threatening issues stemming from iron overload in infants?

    <p>Sideroblastic anemia</p> Signup and view all the answers

    What is the primary cause of a-Thalassemia?

    <p>Inherited deletions affecting a-globin chain synthesis</p> Signup and view all the answers

    Which condition is characterized by the deletion of two a-globin genes?

    <p>Thalassemia Trait</p> Signup and view all the answers

    What is a characteristic feature of Hemoglobin H Disease?

    <p>Moderately severe anemia due to reduced alpha chain synthesis</p> Signup and view all the answers

    What is the clinical implication of the Silent Carrier State?

    <p>They are asymptomatic with slight microcytosis</p> Signup and view all the answers

    Which statement regarding Hydrops Fetalis is true?

    <p>Excess y-globin chains result in poor oxygen delivery.</p> Signup and view all the answers

    What is the genetic basis of Paroxysmal Nocturnal Hemoglobinuria?

    <p>Acquired mutation in the PIGA gene</p> Signup and view all the answers

    What clinical risk is associated with Hydrops Fetalis survivors?

    <p>Dependence on lifelong blood transfusions</p> Signup and view all the answers

    Which complication is associated with Hemoglobin H Disease?

    <p>Cellular inclusions causing spleen phagocytosis</p> Signup and view all the answers

    What is the expected outcome if all four a-globin genes are deleted?

    <p>Hydrops fetalis with severe anemia</p> Signup and view all the answers

    Which of the following describes the pathology of Paroxysmal Nocturnal Hemoglobinuria?

    <p>RBC membrane defect resulting in hemolysis</p> Signup and view all the answers

    Which inherited disorder is caused by mutations in globulin genes resulting in decreased synthesis of hemoglobin?

    <p>Thalassemia</p> Signup and view all the answers

    What is the primary cause of hemolytic anemia arising from mechanical trauma to red blood cells?

    <p>Defective cardiac valve prostheses</p> Signup and view all the answers

    In megaloblastic anemia, which vitamin deficiency is typically linked with ineffective hematopoiesis?

    <p>Folate</p> Signup and view all the answers

    What is the mechanism by which immunohemolytic anemia causes the destruction of red blood cells?

    <p>Antibodies binding to red blood cell antigens</p> Signup and view all the answers

    Which statement about hemolytic disease of the newborn is correct?

    <p>It results from blood group incompatibility between mother and fetus.</p> Signup and view all the answers

    What is a key characteristic of pernicious anemia?

    <p>Lack of intrinsic factor</p> Signup and view all the answers

    Which type of hypersensitivity reaction is implicated in hemolytic disease of the newborn?

    <p>Type II</p> Signup and view all the answers

    Which mechanism leads to megaloblastic changes seen in vitamin deficiencies?

    <p>Impairment of DNA synthesis</p> Signup and view all the answers

    What distinguishes G6PD deficiency?

    <p>Oxidative stress leading to hemolysis</p> Signup and view all the answers

    What type of anemia is characterized by the detection of antibodies on the patient's red blood cells?

    <p>Immunohemolytic anemia</p> Signup and view all the answers

    What condition is often associated with megaloblastic anemia due to impaired absorption of vitamin B12?

    <p>Gastrectomy</p> Signup and view all the answers

    What can cause microangiopathic hemolytic anemia?

    <p>Microvascular thrombi</p> Signup and view all the answers

    What is a common result of Vitamin B12 deficiency in infants?

    <p>Neural tube defects</p> Signup and view all the answers

    Study Notes

    Red Blood Cell Anemias

    • Red blood cells (RBCs) are deformable, non-nucleated, biconcave disks.
    • The average human adult has more than 5 liters (6 quarts) of blood in their body.
    • An average-sized man has about 12 pints.
    • An average-sized woman has about nine pints.
    • RBCs are the most abundant blood cell.
    • When blood is separated, the red cell portion is about 45% of the total volume (hematocrit).
    • RBCs carry oxygen and nutrients to all cells and remove waste products.
    • Hemoglobin is responsible for the red color of the cells.
    • The cell membrane provides deformability and stability.
    • RBCs take up oxygen in the lungs and release it into tissues.
    • RBCs live in the blood circulation for about 100-120 days.
    • RBC production is called erythropoiesis.
    • RBCs are made in the bone marrow from stem cells.
    • 2-3 million RBCs are produced per second in human adults.
    • The reticulocyte is a precursor of the RBC, released at a steady state in the bone marrow.
    • A shift in release earlier than usual is called a stress reticulocyte.
    • The cells are formed in the bone marrow by stem cells.
    • The cells in the blood are formed in the bone marrow by the stem cells.
    • Erythrocytes are the red blood cells.
    • Leukocytes are the white blood cells.
    • Megakaryocytes are the platelets.
    • The production of blood cells begins in the yolk sac early in embryonic development; later the liver and lymphatic organs take over, then the red bone marrow is the only site.

    Blood

    • The average human adult has more than 5 liters (6 quarts) of blood in their body.
    • An average-sized man has about 12 pints of blood in his body.
    • An average-sized woman has about nine pints.
    • Whole blood runs through the veins, arteries, and capillaries.
    • Blood is composed of formed elements (cells and cell fragments) suspended in a liquid fraction called plasma.
    • Blood carries oxygen and nutrients to all the cells and removes waste products.
    • Blood also delivers the cells of the immune system to help fight infection and contains platelets that can form a plug in a damaged blood vessel to prevent blood loss.
    • Through the circulatory system, blood adapts to the body's needs.

    Plasma

    • Plasma is composed of 90% water and a mixture of water, sugar, fat, proteins, and salts.
    • It acts as a solvent, suspends blood components, assists in adsorption of molecules, and transports thermal energy.
    • Proteins make up 7% of plasma, composed of over 100 distinct proteins with specific functions and create colloid osmotic pressure.
    • Protein types include albumin, globulins (immunoglobulins), and fibrinogen.
    • Other solutes include electrolytes, nutrients, gases, regulatory substances, and waste products.
    • Plasma contains clotting factors, antibodies, enzymes, hormones, glucose, and fat particles.
    • Plasma transports blood cells, nutrients, waste products, antibodies, clotting proteins, chemical messengers, and proteins maintaining fluid balance.

    Blood Composition

    • Blood is a specialized fluid with four main components:
    • Plasma
    • White blood cells
    • Platelets
    • Red blood cells.

    Blood Structure

    • Plasma makes up about 60% of blood.
    • The middle layer is composed of white blood cells and platelets.
    • The bottom layer is red blood cells.
    • Plasma is the liquid part of the blood.
    • White blood cells are involved in the immune system.
    • Platelets are involved in blood clotting.
    • Red blood cells are involved in carrying oxygen.

    Hematopoiesis

    • The production of blood cells.
    • Begins early in embryonic development in the yolk sac.
    • Later taken over by the liver and lymphatic organs.
    • Finally assumed entirely by the red bone marrow.
    • Precursor of new blood cells is a pool of undifferentiated pluripotential stem cells.

    Erythropoiesis

    • The process of forming and life cycle of red blood cells.
    • Hemocytoblast (stem cell)
    • Proerythroblast (rubriblast)
    • Earliest and latest erythroblast
    • Normoblast (NRBC)
    • Reticulocyte
    • Erythrocyte (RBC)..

    Erythrocytes (Red Blood Cells)

    • Red blood cells are deformable, non-nucleated, and biconcave disks.
    • The most abundant blood cell.
    • When blood is separated by centrifugation the red cell portion is approximately 45% of the total volume (Packed cell volume or hematocrit).
    • The erythrocyte is an oxygen-carrying cell because it is rich in hemoglobin.
    • The biconcave shape provides a large surface area for oxygen diffusion.
    • The mature erythrocyte has no nuclear material, so new protein cannot be synthesized.

    Red Blood Cells

    • In an embryo, the liver is the main site of red blood cell production.
    • Production can be stimulated by the hormone erythropoietin, synthesized by the kidney.
    • Healthy individuals, RBCs live in the blood circulation for about 100 to 120 days.
    • In many chronic diseases, the lifespan of the erythrocytes is markedly reduced.

    Red Blood Cell Count

    • A count of the number of circulating RBCs in 1 mm³ of peripheral venous blood.
    • Normal values vary according to gender and age
    • Women tend to have lower values than men.
    • RBC counts tend to decrease with age
    • Low RBC values are caused by hemorrhage, hemolysis, dietary deficiency, genetic aberrations, drug ingestion, marrow failures, chronic illness, and other organ failure
    • RBC counts greater than normal can be physiologically induced as a result of the body's requirements for greater oxygen-carrying capacity (high attitudes).
    • Diseases that produce chronic hypoxia increase RBC count, such as congenital heart disease.
    • Polycythemia vera is a neoplastic condition causing uncontrolled production of RBCs.
    • Dehydration falsely elevates RBC count.
    • Overhydration falsely lowers RBC count.
    • Automated analysis has a 4-5% error range.

    Red Blood Cells

    • A typical erythrocyte has a disc diameter of approximately 6.2-8.2 um and a thickness of 2-2.5 um.
    • RBCs lack a cell nucleus and most organelles in order to accommodate maximum space for hemoglobin.
    • Approximately 2.4 million new erythrocytes are produced per second in human adults.
    • The cells develop in the bone marrow and circulate for about 100-120 days.
    • Roughly a quarter of the human body's cells are red blood cells.
    • Oxygen-sensing cells in the kidney respond by increasing the production of erythropoietin stimulating the proliferation of the bone marrow to increase red blood cell production.

    Red Blood Cell Count

    • Normal results in pregnancy are lower due to dilution effect of increased body fluid.
    • Nutritional deficiency may be involved in pregnancy anemia.
    • Drugs that may cause increased RBC levels include erythropoietin and gentamicin.
    • Drugs that may cause decreased RBC levels include those that decrease marrow production or cause hemolysis.
    • Collect blood in EDTA (lavender-top tube).
    • Invert the tube 7 times to mix with the anticoagulant.
    • Avoid hemolysis.

    Red Blood Cells

    • When RBCs undergo shear stress in constricted blood vessels, they release ATP, relaxing vessel walls to promote normal blood flow.
    • Human RBCs complete a circulation cycle in about 20 seconds on average.
    • RBCs are produced via erythropoiesis from committed stem cells to mature RBCs over 7 days.
    • Continuous production of RBCs occurs in the red bone marrow of large bones at a rate of about 2 million per second.

    Polychromatic Erythrocyte

    • Up to 1% of cells stain with a purplish tinge and are of greater diameter.
    • Due to residual RNA in the immature erythrocyte.

    Reticulocyte Count

    • Increased reticulocyte counts indicate the bone marrow is releasing an increased number of RBCs into the bloodstream.
    • Usually a response to anemia.
    • The reticulocyte index in a patient with a good marrow response to the anemia should be 1.0
    • If below 1.0, the bone marrow response is inadequate to compensate.
    • Reticulocyte index= Reticulocyte count (%) x Patient's hematocrit.
    • Reticulocyte count (%) is the percentage of reticulocytes in total RBCs.
    • Normal Hematocrit is the reference range.
    • Patient's Hematocrit is the specific patient's level.
    • When elevated, noticeable on a Wright stain peripheral smear; reticulocytes appear as large, polychromatic red blood cells.
    • Anemia due to production defect is associated with a normal to low reticulocyte count.
    • Hyporegenerative anemias include iron deficiency anemia, anemia of chronic disease, lead poisoning, folate deficiency, B12 deficiency, myelodysplastic syndrome, aplastic anemia, and pre-red cell aplasia

    Nucleated Red Blood Smear

    • Visual inspection/analysis of blood cells.

    Abnormal Red Blood Cell Morphology

    • Shows variations in red blood cells in different disorders.
    • Includes red cell morphology findings associated with non-hemolytic and hemolytic conditions.
    • Lists various types, causes, and features.

    Blood Cell Count Normal Ranges

    • RBC x 106/uL or RBC x 1012/L
      • Adult/elderly: Male: 4.7 – 6.1; Female: 4.2 – 5.4
      • Child: ranges by age from 2-18 years

    Interfering Factors

    • Failure to use proper anticoagulant
    • Hemoconcentration due to prolonged tourniquet constriction
    • Hemodilution due to drawing the same arm used for IV infusion of fluids
    • High white blood cell counts
    • Diseases that cause RBCs to agglutinate or form rouleaux
    • Hemolysis due to rough handling

    Hematocrit

    • Indirect measurement of RBC number and volume.
    • Used as a rapid measurement of quantity in blood.
    • Complete blood cell count.
    • Evaluation of anemia patients.
    • Percentage of total blood volume made up by RBCs.
    • Compared to total blood column height after centrifugation.
    • The ratio of the height of the RBC column compared to the original total blood column is multiplied by 100%.

    Hematocrit (Hct)

    • Altered by many factors besides RBC production, including hemodilution, dehydration, abnormal RBC size, pregnancy, high altitudes, and high white blood cell count.
    • Larger RBCs are associated with higher HCT levels.
    • High altitudes increase HCT due to physiologic response to lower oxygen.

    Hemoglobin (Hgb)

    • Measure of total amount of Hgb in peripheral blood.
    • Part of complete blood count.
    • Serves as a vehicle for oxygen and carbon dioxide transport.
    • Important acid-base buffer system.
    • Normal values vary by age and gender.
    • Women tend to have lower values, decreasing with age.
    • Hct in percentage points is roughly three times the Hgb concentration in grams per deciliter when RBCs are normal size and contain normal amounts of Hgb.

    Hemoglobin (Hgb)

    • There is a slight diurnal variation in Hgb levels.
    • Highest around 8 AM, lowest around 8 PM.
    • Heavy smokers tend to have higher Hgb than nonsmokers.
    • Living at high altitudes increases Hgb values due to physiologic response to lower oxygen.
    • Recent blood transfusions may alter test results.

    Hemoglobin Synthesis

    • Globin molecules form tetramers with heme compound joined to each chain.
    • In newborns, fetal hemoglobin consists of two alpha and two gamma globins.
    • Hemoglobin A has two alpha and two beta globin chains accounting for 97% in normal individuals.
    • Fetal hemoglobin has higher oxygen affinity.
    • Remaining hemoglobin comprises Hemoglobin A2 and F.
    • Usually by 12 months of age the gamma globin is replaced with beta globin to form hemoglobin A.
    • Hemoglobin A2 consists of a pair of alpha and delta globin chains.

    Breaking Down Hemoglobin

    • Old or damaged RBCs are removed from circulation by macrophages in the spleen and liver.
    • Hemoglobin is broken down into heme and globin.
    • Globin may be recycled or further broken down into amino acids.
    • Heme iron is conserved and reused in the synthesis of new hemoglobin molecules.

    Mean Corpuscular Volume (MCV)

    • A measure of the average volume or size of a single RBC.
    • Used in classifying anemias.
    • Derived by dividing the hematocrit by the total RBC count.
    • Normal values vary according to age and gender.
    • increased MCV = macrocytic RBC's
    • decreased MCV = microcytic RBC's

    Mean Corpuscular Hemoglobin (MCH)

    • A measure of the average amount of hemoglobin within an RBC.
    • Derived by dividing the total hemoglobin concentration by the number of RBCs.
    • Macrocytic cells generally have more hemoglobin; microcytic cells have less.

    Mean Corpuscular Hemoglobin Concentration (MCHC)

    • A measure of the average concentration or percentage of hemoglobin within a single RBC.
    • Derived by dividing the total hemoglobin concentration by the hematocrit.
    • Low MCHC = hypochromic
    • Normal values = normochromic
    • Increased MCHC = hyperchromic
    • Not all RBCs can be considered hyperchromic.

    Red Blood Cell Distribution Width (RDW)

    • An indication of the variation in RBC size.
    • Calculated by a machine using MCV and RBC values.
    • Variations in the width of RBCs may help classify certain types of anemia
    • Anisocytosis, a condition characterized by variable and abnormal RBC size, is indicated by RDW.

    Red Blood Cell Indices

    • Mean corpuscular volume (MCV):
      • Adult/elderly/child: 80-95 fl
      • Newborn: 96-108 fl
    • Mean corpuscular hemoglobin (MCH)
      • Adults/elderly/child: 27-31 pg
    • Mean corpuscular hemoglobin concentration (MCHC)
      • Adults/elderly/child: 32-36 g/dL
      • Newborns: 32-34 pg
    • Red blood cell distribution width (RDW)
      • Adult: 11%-14.5%
      • Newborn:32-33 g/dL

    Checkpoint Questions (Answers based on the provided slides)

    • (These are answers pulled from the slide decks)*

    Anemia

    • Present when hemoglobin and hematocrit are reduced, characterized by low oxygen transport capacity.
    • Classified by red cell size (MCV) and hemoglobin content (MCH). Diagnostic tests involve microscopic examination of red blood cell morphology (shape) on a blood smear.
    • Result from blood loss (hemorrhage), red cell destruction (hemolysis), or reduced red blood cell production.
    • Hemolytic anemias can be intrinsic or extrinsic.
    • Premature destruction can happen in the bloodstream (intravascular hemolysis) or within reticuloendothelial system (extravascular hemolysis).

    Intravascular Hemolysis

    • Caused by red cell trauma, mechanical heart valves, complement fixation, ABO incompatibility, paroxysmal cold hemoglobinuria(PCH), snake envenomation, and infections like malaria, babesiosis, and clostridia.

    Extravascular Hemolysis

    • The cause of hemolysis may be inherited or acquired.
    • Inherited forms of hemolytic anemia usually present in early childhood.

    Hemolytic Anemia

    • Presents with jaundice, fatigue, tachycardia, and pallor.
    • Chronic hemolysis leads to pigmented gallstones.
    • Intravascular hemolysis may present with dark urine and back pain. Leg ulcers in sickle cell disease and hereditary spherocytosis.
    • Splenomegaly is common with extravascular hemolysis.

    Blood Diseases Involving Red Blood Cells

    • Anemia is a reduction in total circulating red blood cell mass below normal limits.
    • Characterized by low oxygen transport capacity of the blood, with several causes like excessive breakdown of red blood cells (hemolysis), diseases, and increased red blood cell destruction.
    • Polycythemias are diseases characterized by a surplus of red blood cells, and the increase in blood's viscosity can cause a number of symptoms.
    • Hemolytic transfusion reaction is donated red blood cell destruction mediated by host antibodies.
    • Oxygen carrying capacity deficit is compensated by adaptive increase in the plasma volume.

    Classification of Anemia by Pathophysiology

    • Categorizes anemia based on production or survival defects.

    Chronic Blood Loss

    • Anemia only occurs when the rate of loss exceeds the regeneration capacity of the marrow, or when iron reserves are depleted.
    • Iron deficiency anemia is the most common type.

    Hemolytic Anemia

    • Features include defect of the red cell, usually hereditary.
    • Result from abnormalities outside the red cell, shortened red blood cell lifespan below 120 days.
    • Elevated erythropoietin levels, compensatory increase in erythropoiesis.
    • Accumulation of hemoglobin degradation products.
    • Caused by intrinsic red blood cell defects.
    • Damage induced by extrinsic factors that increase red cell destruction.

    Hemolytic Anemia

    • Physiological destruction of red cells in spleen , liver and bone marrow.
    • Age dependent changes causes recognition or phagocytosis.
    • Extravascular hemolysis involves premature destruction of red cells within phagocytes.
    • Results in reduced deformability.

    Pathogenesis of Hemolytic Anemia

    • Hyperbilirubinemia, jaundice due to hemoglobin degradation by macrophages.
    • Splenomegaly due to work hyperplasia of phagocytes in the spleen.
    • Bilirubin-rich gallstones.
    • Increased risk of secondary cholecystitis (bile duct obstruction).

    Anemia, Oxygen, and Adaptive Compensations

    • Anemia lowers oxygen-carrying capacity.
    • Anemia may result from blood loss, increased red blood cell destruction, and decreased red blood cell production.
    • Adaptive compensation includes increased plasma volume , cardiovascular output, respiratory rate, and other metabolic changes enhancing oxygen delivery to tissues.

    Intravascular Hemolysis

    • Can be caused by mechanical injury.
    • Trauma-caused cardiac valves, turbulent flow.
    • Thrombotic narrowing of the microcirculation.
    • Repetitive physical trauma (marathon running).
    • Caused by damage severe enough to burst red blood cells within circulation.
    • Complement fixation; Antibodies bind to and recognize red blood cell antigens.
    • Infections or disease like malaria.
    • Exogenous toxic factors, such as from Clostridia

    Plasmodium Infection (Malaria)

    • A disease causing hemolysis. An infection.

    Clostridium perfringens with Gas gangrene

    • A condition causing hemolysis. An infection.

    Checkpoint Question (Answers based on the slides)

    Hereditary Spherocytosis

    • An inherited disorder.
    • Results from intrinsic defects in membrane proteins, such as spectrin, causing red blood cell membrane loss and resulting in spherocytes.
    • Splenic sequestration and destruction of red cells.
    • Biconcave erythrocytes are released from the marrow, losing membrane rapidly and assuming a spherical shape.
    • Result = smallest possible diameter for a given volume.

    Hereditary Spherocytosis (HS)

    • Morphologic finding is spherocytosis. Small, dark staining (hyperchromic).
    • Moderate splenomegaly (characteristic finding).
    • Autosomal dominant inheritance pattern (75% of cases).
    • Decreased red blood cell lifespan, average 10-20 days.
    • Extravascular hemolysis in the spleen due to narrow slit passage, preventing red cell passage between red pulp and splenic venous blood vessels.

    Hereditary Spherocytosis (HS)

    • 2/3 of patients have abnormal RBC sensitivity to osmotic lysis
    • RBCs increase mean cell hemoglobin concentration (MCHC) due to dehydration from loss of K+ and H2O.
    • Diagnosis via family history, evidence of extravascular hemolysis, and spherocytes on peripheral blood smears.
    • Splenectomy leads to excellent prognosis in patients with HS, but there is risk of bacterial infections due to lack of splenic function.
    • Risk of aplastic crisis triggered by parvovirus B19 infection, which infects and damages erythroid progenitors in bone marrow.

    Spherocytes

    • No area of central pallor
    • Polychromatic reticulocytes.

    Hereditary Spherocytosis (HS)

    • Mild to moderate chronic hemolytic anemia.
    • Aplastic crisis from parovirus infection.
    • Splenectomy treats symptoms.
    • Diagnosis is based on family history, findings, and laboratory evidence

    Hereditary Elliptocytosis (HE)

    • An inherited disorder.
    • Due to defects in spectrin tetramers leading to ovalocytes.
    • Mostly found in African Americans and usually a mild hemolytic anemia.
    • Hereditary pyropoikilocytosis is a variant where RBCs are sensitive to heat damage.
    • Notable peripheral smear finding is profound poikilocytosis (various shapes and sizes of RBCs).
    • Condition most pronounced in infancy and tends to abate with age.

    Elliptocytosis

    • Peripheral smears showing elliptocytes and ovalocytes.
    • Hereditary elliptocytosis.
    • Hereditary pyropoikilocytosis.
    • Southeast Asian ovalocytosis.

    Hemolytic Disease Due to Red Cell Enzyme Defects: Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

    • G6PD is a necessary enzyme in red blood cells, involved in red blood cell metabolism.
    • Lack of G6PD impairs the reduction of glutathione, protecting against oxidative damage.
    • RBCs prone to damage and hemolysis.
    • Deficiency or defect of G6PD results in impaired reduction of glutathione, which leads to oxidative damage to the RBCs.
    • Abnormalities in hexose monophosphate shunt or glutathione metabolism reduce oxidative injury resistance and lead to hemolysis.

    G6PD Deficiency

    • Inherited condition.
    • Body lacks enough G6PD (glucose-6- phosphate dehydrogenase).
    • This enzyme helps red blood cells work properly.
    • Lack of G6PD can cause hemolytic anemia.
    • Red blood cells break down faster than they are made.
    • G6PD deficiency catalyzes the conversion of NADP+ to its reduced form NADPH, important for the pentose phosphate pathway.

    G6PD Deficiency

    • Shows spherocytes, nucleated red cells, and blister cells.
    • Hemighost and irregularly contracted red cells are seen.

    Hemolytic Disease Due to Red Cell Enzyme Defects: Glucose-6-Phosphate Dehydrogenase (G6PD)

    • G6PD deficiency is an inherited X-linked trait, increasing risk for symptomatic disease in males.
    • Several hundred G6PD genetic variations are known, but most are harmless.
    • Two variant forms, called G6PD and G6PD Mediterranean, cause clinically significant hemolytic anemia.
    • G6PD is present in about 10% of African-American and Middle Eastern populations.
    • This is associated with natural protection against Plasmodium falciparum.

    Hemolytic Disease Due to Red Cell Enzyme Defects: Glucose-6-Phosphate Dehydrogenase (G6PD)

    • G6PD variants affect the protein folding thus increasing susceptible to proteolytic degradation.
    • Enzyme activity falls quickly and results in inadequate protection against oxidant stress as red cells age.
    • Older red cells are more susceptible to hemolysis. Infections, free radicals from activated leukocytes are common causes of triggers.
    • Infections can also trigger hemolysis.
    • Drugs such as antimalarials, sulfonamides, and nitrofurantoin are triggers.
    • Fava beans may cause hemolysis.

    Sickle Cell Disease

    • Common autosomal recessive disorder.
    • Single point mutation in the beta globin chain of hemoglobin.
    • Results in sickle hemoglobin (HbS), replacement of glutamate with valine.
    • Normal adult red cells have mainly hemoglobin A (a2B2) and fetal hemoglobin (HbF).
    • The high frequency in populations of African descent, the Middle East, or the Indian subcontinent is linked to protective effects against malaria.

    Sickle Cell Disease

    • Depending on the substitution site there are four main functional defects.
    • Hemoglobin becomes crystalline at low oxygen, causing hemolysis and microvascular occlusion.
    • Unstable hemoglobin leads to chronic hemolysis and Heinz bodies (inclusions of denatured hemoglobin).
    • Hemoglobin with increased oxygen affinity may cause polycythemia.
    • Hemoglobin in an oxidized state may cause cyanosis.

    Checkpoint Question (Answer based on the slide deck)

    Thalassemia

    • Inherited disorder due to abnormalities in alpha or beta globin chain synthesis.
    • Imbalance in globin chain synthesis leads to anemia, tissue hypoxia, and red cell hemolysis. Beta-thalassemia major: severe, transfusion-dependent anemia, splenomegaly, marrow expansion, bony deformities, and premature death.
    • Beta-thalassemia minor: clinically mild.
    • Alpha-thalassemias: include disorders with intrauterine death, severe anemia, and clinically insignificant disease.

    Thalassemia

    • Globin chains are of normal composition, but their synthesis rate (alpha or beta) is reduced and damaged.
    • Excess unaffected globin chains damage the developing and mature erythrocytes.
    • Each chromosome 16 has a pair of alpha-globin genes, for a total of four genes in a normal functional cell.
    • Alpha-thalassemia syndromes result from the deletion of one, two, three, or four alpha-globin genes.
    • Beta-thalassemia is caused by defects in the synthesis of beta-globin chains.

    Thalassemia Syndromes

    • Heterogeneous group of disorders.
    • Result from acquired mutations decreasing the synthesis of a- or b-globin chains.
    • Imbalance in globin chain synthesis leads to anemia, tissue hypoxia, and red cell hemolysis.
    • Two alpha chains in HbA are encoded by identical pairs of a-globin genes on chromosome 16.
    • Two beta-chains are encoded by a single B-globin gene on chromosome 11.
    • B-thalassemias are caused by deficient synthesis of the B-chains.
    • A-thalassemias are caused by deficient synthesis of the a-chains.

    Thalassemia Syndromes

    • Endemic in Mediterranean basin, Middle East, tropical Africa, and parts of Asia and Indian subcontinent.
    • Reduced red cell production, reduced red cell lifespan.
    • B-Thalassemia Major: is the most common form in Mediterranean countries, parts of Africa, and Southeast Asia.
    • In nontransfused patients, hemoglobin levels are 3-6 gm/dl.
    • Red cells may completely lack HgA (B°/B0 genotype) or contain small amounts (B+/B+ or B°/B+ genotypes).

    Beta-Thalassemia Major

    • Also known as Mediterranean or Cooley's anemia.
    • Severe microcytic, hypochromic anemia, usually first appearing at 2-6 months of age.
    • Results from having two genes responsible for beta-thalassemia.
    • Blood picture has a significant number of a compensatory increase of gamma chain production leading to the dominance of HbA with only 1% of residual fetal hemoglobin.

    B-Thalassemia Major Morphology

    • Blood smears generally display severe red cell abnormalities which include anisocytosis, poikilocytosis (various shape), microcytosis (small size), and hypochromia (pale appearance).
    • Elevated reticulocyte counts are also seen.
    • Variable numbers of poorly hemoglobinized nucleated red cells.

    Beta Thalassemia Major Morphology

    • Polychromasia, a disorder where there is an abnormally high number of immature red blood cells, found in blood stream.
    • Result of premature release from bone marrow.
    • Codocytes or target cells are a sign of the disorder, which appear as having a dark center (hemoglobinized area), surrounded by a paler ring, (area of relative pallor), with a dark outer/peripheral, second ring containing a band of hemoglobin.

    Thalassemia Major Morphology

    • Shows microspherocytes, polychromasia.
    • Hemolytic blood picture.

    B-Thalassemia Minor

    • More common than B-thalassemia major.
    • Heterozygous carriers of the B+ or Bº allele.
    • Usually asymptomatic.
    • Mild anemia.
    • Peripheral blood smear shows some red cell abnormalities (hypochromia, microcytosis, basophilic stippling, and target cells).
    • Mild erythroid hyperplasia in bone marrow.
    • Hemoglobin electrophoresis shows an increase in HgA2.

    Thalassemia Minor Morphology

    • The smears show small, pale (hypochromic), variously-shaped (poikilocytosis) red blood cells.
    • Able to carry less oxygen compared to normal RBCs.

    Thalassemia Minor Morphology

    • shows small, pale (hypochromic), variously-shaped (poikilocytosis) red blood cells, and are able to carry less oxygen compared to normal red blood cells.

    a-Thalassemia

    • Caused by inherited deletions leading to reduced or absent a-globin chain synthesis.
    • Normally, there are four a-globin genes.
    • Severity depends on how many a-globin genes are affected.
    • Anemia stems from lack of proper hemoglobin (excess of unpaired globin chains).
    • Classified based on the number of deleted a-globin genes.

    Silent Carrier State

    • Associated with deletion of a single a-globin gene.
    • Barely detectable reduction in a-globin chain synthesis.
    • Completely asymptomatic but have slight microcytosis.

    Thalassemia Trait

    • Deletion of two a-globin genes from a single chromosome (a/a-/-) or one a-globin gene from each of two chromosomes (a/-/a/-).
    • Similar quantitative deficiencies of a-globin
    • Clinically identical but have implications for their children ( a-thalassemia (HbH) disease or hydrops fetalis).

    Hemoglobin H Disease

    • Result from deletion of three a-globin genes.
    • Most common in Asian populations.
    • Normal a-globin gene results in markedly reduced alpha chain synthesis, tetramerization of beta-globin chains.
    • High oxygen affinity, insufficient oxygen delivery leading to tissue hypoxia.
    • Prone to oxidation, forming precipitates and intracellular inclusions promoting red cell sequestration and phagocytosis in the spleen.
    • Moderatley severe anemia.

    Hydrops Fetalis

    • Most severe form of a-thalassemia due to deletion of all four a-globin genes.
    • Excess gamma-globin chains form tetramers (hemoglobin Barts), with high oxygen affinity delivering little oxygen to tissues.
    • Fetal distress, leading to in utero death or shortly after birth.
    • Intrauterine transfusions may help infants survive.
    • Severe pallor, generalized edema, massive hepatosplenomegaly
    • Lifelong transfusion dependence and iron overload risk.
    • Hematopoietic stem cell transplantation can be curative

    Paroxysmal Nocturnal Hemoglobinuria

    • Acquired genetic defect impacting the PIGA gene's function (essential for complement regulatory protein production).
    • Causes RBC membrane defects, increasing susceptibility to complement-mediated lysis.
    • X-linked, subject to random inactivation of one X-chromosome in cells of females.
    • Mutation in PIGA gene sufficient to produce deficiency state.
    • Incidence is 2-5 per million in the United States.
    • Hemolysis in PNH causes dark urine, due to RBC lysis, and anemia.

    Checkpoint Question (Answer based on the slide deck)

    Immunohemolytic Anemia

    • Caused by antibodies binding to red cells, leading to premature destruction.
    • Diagnosis involves detecting antibodies and/or complement on red cells.
    • Direct Coombs test mixes patient's red blood cells with sera containing antibodies for human immunoglobulins or complement.
    • Visible clumping (agglutination) indicates antibody presence.
    • Antibody type: warm or cold agglutinin.

    Hemolytic Anemia from Trauma to Red Cells

    • Seen in individuals with cardiac valve prostheses and microangiopathic disorders.
    • Artificial mechanical cardiac valves are more often implicated than bioprosthetic valves.
    • Hemolysis from shear forces and pressure gradient across damaged valves.
    • Microangiopathic hemolytic anemia frequently seen with disseminated intravascular coagulation (DIC), thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), malignant hypertension, and disseminated cancer.

    Mechanical Trauma to Red Cells

    • Intravascular hemolysis due to abnormal mechanical forces.
    • Traumatic hemolysis from defective cardiac valves.
    • Microangiopathic hemolytic anemia occurs when small vessels become narrowed by thrombi.
    • Disseminated intravascular coagulation (DIC).

    Anemias of Diminished Erythropoiesis

    • Megaloblastic anemia (impairment of DNA synthesis).
    • Vitamin B12 deficiency (decreased intake or impaired absorption).
    • Folic acid deficiency (decreased intake, increased requirement, or impaired utilization).

    Immunohemolytic Anemia

    • Caused by antibodies that bind to antigens on red cell membranes.
    • May arise spontaneously or be induced by drugs or chemicals.
    • Classified based on the nature of the antibody and presence of predisposing conditions.

    Hemolytic Disease of the Newborn

    • Cytotoxic, responsible for tissue damage in hemolytic disease of the newborn.
    • Antigen on the plasma membrane is first identified as foreign; B cells become sensitized and ready to produce antibodies upon subsequent antigen exposure.
    • Antibodies produced bind to antigens activating complement.
    • Fetal inherits red-cell antigens from the father, foreign to the mother.
    • Fetal red cells enter maternal circulation during pregnancy or childbirth, sensitizing the mother to paternal red-cell antigens.
    • Antibodies that cross the placenta cause hemolysis of fetal red cells.

    Type II Hypersensitivity Reaction

    • Cytotoxic, responsible for tissue damage in hemolytic disease of the newborn.
    • Antigen on a plasma membrane first recognized as foreign.
    • B cells become sensitized and ready for antibody production upon subsequent antigen exposure.
    • Antibodies bind to antigen and activate complement.

    Folate Deficiency

    • Folate and vitamin B12 deficiencies are classical causes of megaloblastic anemia.
    • Affects hematopoietic precursor cells and nuclei in the bone marrow, which appear large and immature (maturation being behind cytoplasmic maturity).
    • This affects not only erythroblasts, but other rapidly dividing cells like granulocytes , megakaryocytes and enterocytes.
    • Results from impairment of DNA synthesis.
    • Erythropoiesis becomes ineffective, resulting in hypercellular marrow.
    • Many erythroblasts are destroyed in the marrow.
    • Folic acid deficiency does not cause the same neurologic defect as vitamin B12 deficiency.
    • Folate supplementation in early pregnancy reduces neural tube defects.

    Pernicious Anemia

    • Specific form of megaloblastic anemia.
    • Caused by autoimmune gastritis impairing intrinsic factor production, required for vitamin B12 absorption from the gut.
    • Humans rely on dietary vitamin B12 absorption aided by intrinsic factor.
    • Vitamin B12 is a complex, organometallic compound.
    • This is absorbed in the duodenum by associating with intrinsic factor, facilitated by the action of pancreatic proteases, after being freed from binding proteins (haptocorrin).
    • The parietal cells of the fundic mucosa secrete intrinsic factor.

    Pernicious Anemia

    • Occurs in all racial groups but more prevalent in Scandinavian and other Caucasian populations, typically in older adults (median age 60).
    • Believed to result from an autosomal attack on the gastric mucosa.
    • Strong genetic predisposition suspected, but no definite genetic pattern has been discovered.

    Vitamin B12

    • Important for metabolism, red blood cell formation, and nervous system maintenance, including the brain and spinal cord.

    Pernicious Anemia- B12

    • A specific type of anemia caused by a lack of intrinsic factor (protein needed for vitamin B12 absorption).
    • Without sufficient B12, the body cannot produce a sufficient amount of healthy red blood cells.
    • Megaloblastic: describes abnormally large and immature red blood cells (megaloblasts) seen in the bone marrow.
    • Hypersegs: likely refers to hypersegmented neutrophils, a type of white blood cell involved in the body's immune response.

    Pernicious Anemia

    • Shows a blood smear.

    Macrocytic Red Blood Cells

    • Blood smear showing macrocytic red cells.

    Iron Deficiency Anemia

    • Cytoplasm of the marrow erythroblast is the predominant site of hemoglobin production, where iron molecules are incorporated.
    • Iron from the diet is absorbed in the duodenum, carried by transferrin to the marrow, internalized into erythroblasts.
    • Iron not utilized in heme is stored bound to ferritin.
    • When iron intake is inadequate or excessive iron loss occurs, ferritin-iron stores of reticuloendothelial system are depleted.
    • Results in red blood cells produced containing insufficient hemoglobin; red blood cells are hypochromatic and microcytic.
    • Fewer mature red cells produced, lowering hematocrit.

    Iron Deficiency Anemia

    • Common nutritional disorder globally,
    • Clinical signs and symptoms primarily related to inadequate hemoglobin synthesis.
    • High prevalence in developing countries, especially in adolescent females and females of childbearing age.
    • Iron's recycling between functional and storage pools, carried within plasma in iron-binding glycoprotein called transferrin which is synthesized in the liver.
    • Normal individuals serum transferrin is about one-third saturated with iron.

    Iron Deficiency Anemia

    • Function of plasma transferrin is to deliver iron to cells.,
    • Free iron is highly toxic, must be sequestered.
    • This is achieved through ferritin, a protein-iron complex found at highest levels in the liver, spleen, bone marrow, and skeletal muscles (stores iron) .

    Iron Deficiency Anemia

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    Hematology - Red Blood Cell and Anemia 11-24 PDF

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    Test your knowledge on red blood cell characteristics, including anisocytosis and macrocytosis. This quiz covers definitions, possible anemia traits, and factors affecting red blood cell counts. Challenge yourself to identify key properties like Mean Corpuscular Volume (MCV).

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