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Questions and Answers
What primarily characterizes the mechanism of sickle cell disease?
What primarily characterizes the mechanism of sickle cell disease?
Which symptom is NOT typically associated with sickle cell anemia?
Which symptom is NOT typically associated with sickle cell anemia?
What is the consequence of substituting glutamic acid with valine at position 6 of the β chain?
What is the consequence of substituting glutamic acid with valine at position 6 of the β chain?
In the diagnosis of hemoglobinosis M, what specific mutation is involved?
In the diagnosis of hemoglobinosis M, what specific mutation is involved?
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Which laboratory examination is deemed mandatory for diagnosing anemia related to hemoglobinopathies?
Which laboratory examination is deemed mandatory for diagnosing anemia related to hemoglobinopathies?
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Which of the following conditions is NOT associated with the presence of microspherocytes?
Which of the following conditions is NOT associated with the presence of microspherocytes?
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What is a common method to assess osmotic fragility in hereditary spherocytosis?
What is a common method to assess osmotic fragility in hereditary spherocytosis?
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In the context of hereditary spherocytosis, how does incubation affect autohemolysis rates?
In the context of hereditary spherocytosis, how does incubation affect autohemolysis rates?
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Which of the following is a known cause of microspherocyte formation?
Which of the following is a known cause of microspherocyte formation?
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What type of laboratory test can help distinguish hereditary spherocytosis from other hemolytic anemias?
What type of laboratory test can help distinguish hereditary spherocytosis from other hemolytic anemias?
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What is the primary cause of hemolysis in β-thalassemia?
What is the primary cause of hemolysis in β-thalassemia?
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Which statement regarding Cooley's anemia is correct?
Which statement regarding Cooley's anemia is correct?
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In the bone marrow of a person with β-thalassemia, which of the following is likely to be observed?
In the bone marrow of a person with β-thalassemia, which of the following is likely to be observed?
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What blood smear characteristic is commonly seen in β-thalassemia?
What blood smear characteristic is commonly seen in β-thalassemia?
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Which test is most significant for diagnosing hemolysis in β-thalassemia?
Which test is most significant for diagnosing hemolysis in β-thalassemia?
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What is the expected hemoglobin level in a patient with severe β-thalassemia?
What is the expected hemoglobin level in a patient with severe β-thalassemia?
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Which laboratory finding indicates inefficient erythropoiesis in β-thalassemia?
Which laboratory finding indicates inefficient erythropoiesis in β-thalassemia?
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Which of the following is NOT a typical red blood cell feature in β-thalassemia?
Which of the following is NOT a typical red blood cell feature in β-thalassemia?
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What is the primary purpose of erythrokinetics?
What is the primary purpose of erythrokinetics?
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Which method involves analyzing the morphology of cells in blood samples?
Which method involves analyzing the morphology of cells in blood samples?
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What does microcytosis indicate in a blood sample?
What does microcytosis indicate in a blood sample?
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Which of the following is a characteristic of macrocytosis?
Which of the following is a characteristic of macrocytosis?
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What is essential for directly evaluating the proliferative state of the bone marrow?
What is essential for directly evaluating the proliferative state of the bone marrow?
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What does the Prince-Jones curve represent?
What does the Prince-Jones curve represent?
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Which condition is NOT associated with macrocytosis?
Which condition is NOT associated with macrocytosis?
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What factors can influence the reliability of evaluating erythrocyte levels in bone marrow?
What factors can influence the reliability of evaluating erythrocyte levels in bone marrow?
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What is indicated by a positive cyclization test after mixing blood with metabisulfite?
What is indicated by a positive cyclization test after mixing blood with metabisulfite?
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What role does intrinsic factor (IF) play in vitamin B12 absorption?
What role does intrinsic factor (IF) play in vitamin B12 absorption?
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Which type of anemia is characterized by chronic hemolytic anemia with jaundice and splenomegaly?
Which type of anemia is characterized by chronic hemolytic anemia with jaundice and splenomegaly?
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What does the presence of Heinz bodies in erythrocytes indicate?
What does the presence of Heinz bodies in erythrocytes indicate?
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Which of the following statements is true regarding vitamin B12 storage in the human body?
Which of the following statements is true regarding vitamin B12 storage in the human body?
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What are the active coenzymes derived from vitamin B12?
What are the active coenzymes derived from vitamin B12?
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Which laboratory finding would most likely be associated with thalassemia?
Which laboratory finding would most likely be associated with thalassemia?
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What is the consequence of membrane alterations caused by Heinz body formation?
What is the consequence of membrane alterations caused by Heinz body formation?
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What is the primary mechanism of vitamin B12 absorption in the body?
What is the primary mechanism of vitamin B12 absorption in the body?
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How is vitamin B12 excreted from the human body?
How is vitamin B12 excreted from the human body?
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What kind of hemoglobin electrophoresis result is typically seen in patients with unstable hemoglobins?
What kind of hemoglobin electrophoresis result is typically seen in patients with unstable hemoglobins?
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In which evolutionary group is survival considered benign and compatible with normal lifespan?
In which evolutionary group is survival considered benign and compatible with normal lifespan?
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What stimulates the synthesis of intrinsic factor (IF)?
What stimulates the synthesis of intrinsic factor (IF)?
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Which transport proteins are responsible for the distribution of vitamin B12 after erythrocyte utilization?
Which transport proteins are responsible for the distribution of vitamin B12 after erythrocyte utilization?
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What type of anemia presents with normocytic normochromic findings but shows significant changes in the smear?
What type of anemia presents with normocytic normochromic findings but shows significant changes in the smear?
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What condition is indicated by over 10% erythroblasts found in the periphery?
What condition is indicated by over 10% erythroblasts found in the periphery?
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Study Notes
Diagnosis of Erythrocyte Production and Destruction
- Erythropoiesis, granulocytopoiesis, and thrombocytopoiesis are all ensured by hematopoietic bone marrow at birth.
- Erythrokinetics encompasses the production, circulation, and destruction of erythrocytes.
- Impaired or inefficient erythropoiesis leads to fewer peripheral erythrocytes.
- Damaged or destroyed erythrocytes impact the balance between efficient and inefficient erythropoiesis.
Methods for Evaluating Erythrokinetics
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Direct methods include:
- Peripheral blood cell counts (hemoglobin, hematocrit) and nucleated elements in bone marrow.
- Morphological examination of peripheral blood (blood smear) and bone marrow.
- Lifespan of erythrocytes using radioactive labeling with 51Cr or 32P.
- Plasma iron turnover (dosage of sideremia).
- Urine bilirubin excretion (UBG).
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Indirect methods include determination of blood volume and erythrocyte mass. Isotopic dilution methods are used for these. Results depend on factors like body weight, age, and sex.
Normal Aspects of the Blood Smear
- Size (anisocytosis): Red blood cell (RBC) sizes vary normally across different ages, reflecting developmental patterns according to the Prince-Jones curve.
- Microcytosis: RBC size less than 7.2 μm, commonly linked to anemia.
- Macrocytosis: RBC size greater than 12 μm, associated with megaloblastic anemia, cirrhosis, and CO intoxications.
Tinctoriality
- Hypochromia: Reduced hemoglobin concentration, often associated with microcytosis. Annular cells often present.
- Hyperchromia: Changes in RBC thickness, usually seen in macrocytes and spherocytes.
Other Erythrocyte Abnormalities
- Anisochromia: Normal and hypochromic erythrocytes
- Acromocytosis: Degenerated erythrocytes with crescent appearance
- Target cells: (Mexican hat) hemoglobin centrally and on edges of RBC
- Basophilic erythrocytes: Erythroblasts (young RBCs) that lose their nucleus.
- Polychromatophilic erythrocytes: Large immature RBCs, often violet colored.
- Basophilic punctations: Blue spots in RBCs, a sign of nuclear remnants.
- Jolly bodies: Round, purple stained red blood cell remnants
- Cabot rings: Erythrocyte ring-like remnant of nuclear substance
- Azurophilic granules/chromatin powder: Chromatin remnants appearing in purple stain or in rare cases red/purplish
- Poikilocytosis: Non-normal shapes.
- Spherocytes: Uniform colored ring (Ø= 4μm), often in congenital hemolytic jaundice, sickle cells & S hemoglobinosis
- Ovalocytes: Oval morphology.
- Sickle cells: Characteristic shape, in sickle cell anemia and S hemoglobinosis
- Schizocytes: Irregular fragments of erythrocytes, indicative of hemolytic anemias.
The Myelogram
- Myelogram - a method to assess erythroid activity in bone marrow.
- Evaluation of cellularity density
- Ratio between granulocytic to the number of erythroblasts
Maturation Stage (Criterion for evaluating Marrow Production)
- Maturity of erythroblasts (immature precursors) expressed as a percentage
- Normal values for pro-, basophilic, polychromatophilic, and oxyphilic erythroblasts are provided.
- Ratio of polychromatophilic erythroblasts and oxyphilic erythroblasts reflects normal marrow production.
Reticulocytes
- Reticulocytes are the last stage of erythroblast maturation.
- They are an important marker of the efficiency of erythropoiesis.
- Reticulocyte counts are a proxy to assess the body's ability to produce RBCs via erythropoiesis, and in cases of hyperhemolysis.
- Hemolysis accounts for the production of increased reticulocytes.
- Normal values (0.5-1.5%) of reticulocytes are provided as an index for erythropoiesis.
Life Span of Erythrocytes
- Normal life span of erythrocyte is around 120 days.
- Destruction processes include:
- Splenic destruction.
- Occult hemorrhages (small internal bleeds).
- The balance (isocythemia) between production and consumption of erythrocytes is achieved through effective erythropoiesis.
Plasma Iron Turnover
- Includes sideroblasts (iron-containing erythroblasts)
- Hemosiderin (iron-storage substance in tissue)
- Total transferrin iron binding capacity (CT): 15 γ % ml serum
- Latent Fe binding capacity of transferrin (CL): 215 γ % ml serum
- Saturation coefficient (SC): 0.3
Fecal UBG Excretion
- Allows evaluation of erythrocyte catabolism and phagocytosis of erythroblasts.
- Helpful for assessing erythropoietic activity.
Erythrocyte Constants and Indices
- The number of erythrocytes per microliter of blood
- Hemoglobin concentration in grams per deciliter (g/dL)
- Hematocrit expressed as a percentage in blood
Mean Corpuscular Values
- Mean corpuscular volume (MCV)
- Mean corpuscular hemoglobin (MCH)
- Mean corpuscular hemoglobin concentration (MCHC)
Erythrocyte Destruction/Hemolysis
- Hemolysis is the physiological process of removing senescent erythrocytes.
- Senescent erythrocytes lose their functions (especially O2 transport).
- Changes in membrane composition occur that trigger an immunological response, resulting in the removal by macrophages.
- The limited lifespan of erythrocytes (120 days) causes structural and metabolic changes.
- Hemolysis, if excessive, can lead to anemia despite the compensatory capacity of the bone marrow to increase its production by 7x.
Diagnosis of Hemolysis
- Anamnesis (history or background)
- Clinical examination (pallor, skeletal changes, jaundice).
- Laboratory tests (blood and biochemical examinations that evaluate markers of hemolysis)
- Hematologic examinations
- Biochemical examinations
Intravascular vs. Extravascular Hemolysis
- Most hemolysis is extravascular, occurring in the spleen.
- Intravascular hemolysis involves breakdown of RBCs within the blood vessels.
- Both mechanisms can contribute to hemolytic anemia depending on primary cause.
Degradation of Hemoglobin (Formation of Bilirubin)
- Normal erythrocyte lifespan and breakdown.
- Reticuloendothelial system plays a role.
- Bilirubin is formed through a series of steps, including the breakdown of hemoglobin, isomerization to biliverdin, and reduction to different forms of conjugated bilirubin until its excretion in bile and urine (or stool).
Anemia
- ↓hemoglobin, ↓ hematocrit,↓ in the number of erythrocytes over 10% compared with standard values for age and sex
Classification of Anemia
- Normocytic normochromic
- Microcytic hypochromic (thalassemia, iron deficiency)
- Macrocytic normochromic (megaloblastic)
Hypo/Hyperchromic Anemia
- Hypochromia is low hemoglobin concentration and is frequently associated with anemia
- Hyperchromia is caused by increased hemoglobin concentration.
Classification of Hemolytic Anemia
-
Intrinsic (intracorpuscular) deficits
-
Extrinsic (extravascular) deficits
-
Membrane abnormalities
-
Enzyme deficiencies (G6PD defects)
-
Hemoglobinopathies
-
Paroxysmal nocturnal hemoglobinuria (PNH)
Hereditary Spherocytosis
- Hereditary spherocytosis is a genetic disorder resulting from abnormalities in RBC membrane proteins, causing spherically shaped RBCs.
- Clinical findings include jaundice, splenomegaly, and hemolytic anemia.
- Osmotic fragility test
- Autohemolysis test
Hereditary Elliptocytosis
- Hereditary Elliptocytosis is a genetic disorder resulting in oval-shaped RBCs.
- Clinical symptoms and laboratory findings are similar to other hemolytic anemias.
Hereditary Pyropoikilocytosis (PPK)
- Hereditary Pyropoikilocytosis (PPK) is a rare hemolytic anemia with severe RBC membrane abnormalities.
- PPK results in fragile and easily damaged erythrocytes.
- No definitive treatment.
Enzyme Deficiencies
- Dysfunction of erythrocyte enzymes causes intravascular/extravascular hemolysis, reducing erythrocyte oxygen transport.
G6PD Deficiency
- G6PD deficiency → increased susceptibility to oxidative stress.
- Heinz bodies
- Disorders of G6PD function
- Affected individuals present with episodic hemolytic crises triggered by stressors (like infections and certain medications)
PK Deficiency
- PK deficiency = Non-spherocytic chronic hemolytic anemia.
- Results in abnormally shaped erythrocytes.
- Leads to hemolysis, particularly intrasplenic hemolysis.
- Autohemolysis test.
Hemoglobinopathies
- Defects in the hemoglobin molecule's structure or synthesis.
- Example is sickle cell anemia
- Results in decreased or unstable Hb function and abnormal erythrocyte morphology.
- Causes chronic hemolytic anemia
Thalassemia
- imbalances between amounts of α- and non-α chains of the hemoglobin.
- Qualitative and quantitative defects in the synthesis of normal hemoglobin.
- Results in different forms.
- Severe forms are life-threatening.
Megaloblastic Anemias
- General cellular suffering due to inadequate DNA synthesis.
- Deficiencies of vitamin B12 or folic acid.
- Clinical features include macrocytic, megaloblastic cells and characteristic laboratory findings.
- The development of appropriate treatment requires an understanding of the deficient substrates and the related intracellular pathways (methylation).
Causes of Hemolysis and Iron Deficiency Anemia
- Hemolysis occurs due to a multitude of causes that stem from structural defects to intrinsic/extracorpuscular defects.
- Iron deficiency stems from reduced or inappropriate intake or absorption leading to dietary depletion to deficiency of Fe.
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Description
Test your knowledge on sickle cell disease and related hemoglobinopathies with this quiz. It covers key mechanisms, symptoms, diagnostic mutations, and laboratory examinations vital for understanding these conditions. Perfect for students studying hematology or pathophysiology.
