Hereditary Blood Disorders Quiz

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Questions and Answers

What is a characteristic finding in peripheral blood smears for patients with hereditary pyropoikilocytosis (HPP)?

Spoon-shaped oval cells

Increased osmotic fragility

Bizarre micropoikilocytosis (correct)

Normal red cell indices

Which red cell index is usually decreased in hereditary pyropoikilocytosis (HPP)?

MCV (correct)

Hemoglobin concentration

MCHC

MCH

What is a distinctive feature of Southeast Asian ovalocytosis (SAO) on a blood smear?

Normal red blood cell shape

Budding red blood cells

Characteristic spoon-shaped oval cells (correct)

Presence of elliptocytes

In the context of hereditary elliptocytosis (HE), which of the following statements is true regarding lab findings?

Both osmotic fragility and autohemolysis are normal Signup and view all the answers

What is the normal condition for MCHC in infants with hereditary pyropoikilocytosis (HPP)?

Usually elevated Signup and view all the answers

Which type of red cell morphological change is primarily associated with a defect in vertical interactions?

Spherocytes Signup and view all the answers

Which hereditary condition is classified as a defect affecting membrane morphology?

Hereditary pyropoikilocytosis Signup and view all the answers

Hereditary elliptocytosis is associated with defects in which type of interactions?

Horizontal interactions Signup and view all the answers

Which of the following options does NOT represent a hereditary defect of the red cell membrane?

Chronic lymphocytic leukemia Signup and view all the answers

What is the primary defect resulting in spherocytes in hereditary spherocytosis?

Defect in spectrin-ankyrin-band 3 associations Signup and view all the answers

Which of the following is NOT a characteristic of hereditary pyropoikilocytosis?

Ovalocytes Signup and view all the answers

Which disorder is typified by defects in spectrin self-association?

Hereditary elliptocytosis Signup and view all the answers

Hereditary xerocytosis is characterized by which type of cellular change?

Formation of stomatocytes Signup and view all the answers

What is the primary complication of performing a splenectomy before the age of 6 years?

Increased risk of infections Signup and view all the answers

Which characteristic is associated with Hereditary Elliptocytosis (HE)?

Asymptomatic individuals due to normal erythrocyte life span Signup and view all the answers

Which type of hereditary condition is characterized by moderate to severe hemolysis and typically displays microspherocytes?

Hereditary pyropoikilocytosis Signup and view all the answers

What is the primary defect causing spherocytes in hereditary spherocytosis (HS)?

Defect in vertical interactions Signup and view all the answers

Which finding is characteristic of mild hereditary elliptocytosis (HE)?

More than 30% of RBCs are uniform elliptocytes Signup and view all the answers

What is a common trait of Southeast Asian ovalocytosis (SAO)?

Usually asymptomatic with protective benefits against malaria Signup and view all the answers

What type of elliptoid cell is primarily observed in hereditary pyropoikilocytosis?

Microspherocytes Signup and view all the answers

What additional feature is associated with hereditary pyropoikilocytosis (HPP)?

Cells are misshapen and budding Signup and view all the answers

What is a characteristic of Spherocytic hereditary elliptocytosis?

Clinical course similar to hereditary spherocytosis Signup and view all the answers

Which of the following is NOT a lab finding in severe cases of hereditary elliptocytosis (HE) and hereditary pyropoikilocytosis (HPP)?

Increased haptoglobin levels Signup and view all the answers

What morphological characteristic is observed in spherocytic hereditary elliptocytosis?

Less prominent elliptocytosis with spherocytes Signup and view all the answers

What results from defective spectrin dimer self-association in patients with hereditary pyropoikilocytosis?

Partial spectrin deficiency Signup and view all the answers

Which of the following accurately describes the lifespan of spherocytes after splenectomy?

Normal or near normal lifespan Signup and view all the answers

In the context of hereditary conditions, what does poikilocytosis primarily refer to?

Presence of irregularly shaped RBCs Signup and view all the answers

Which cell type is characterized by transverse bars in hereditary stomatocytic elliptocytosis?

Elliptocytes Signup and view all the answers

What is a common feature observed on the peripheral blood smear in patients with mild hereditary elliptocytosis?

High percentage of elliptocytes Signup and view all the answers

What morphology is observed in the peripheral blood smear of Hst?

Stomatocytosis with a tendency toward macrocytosis Signup and view all the answers

What is true about the MCHC levels in Hxe?

Increased MCHC Signup and view all the answers

Which laboratory finding is associated with hereditary acanthocytosis?

Increased number of acanthocytes in erythrocytes Signup and view all the answers

What is the inheritance pattern of hereditary acanthocytosis?

Autosomal recessive Signup and view all the answers

Which enzyme deficiency is the most common in the hexose monophosphate shunt?

Glucose-6-phosphate dehydrogenase deficiency (G6PD) Signup and view all the answers

What impact does G6PD deficiency have on glutathione levels?

Decreased glutathione levels Signup and view all the answers

What is a clinical consequence of hereditary enzyme deficiencies in red blood cells?

Inability to maintain NADPH levels Signup and view all the answers

What is the relationship between G6PD deficiency and sex linkage?

G6PD deficiency is X-linked recessive Signup and view all the answers

What type of cells are produced as splenic macrophages remove inclusions?

Bite cells Signup and view all the answers

What is the inheritance pattern of Pyruvate Kinase (PK) Deficiency?

Autosomal recessive Signup and view all the answers

What is the major consequence of a lack of ATP in PK Deficiency?

Impairment of the cation pump Signup and view all the answers

What serum levels are typically observed in cases of PK Deficiency?

Moderate increase in unconjugated bilirubin Signup and view all the answers

What happens to the hemoglobin affinity for oxygen in response to a three-fold increase in 2,3-DPG level?

It decreases Signup and view all the answers

What is a key laboratory finding in PK Deficiency?

Negative Coomb's test Signup and view all the answers

What type of red blood cell morphology is typically observed in PK Deficiency?

Normochromic normocytic Signup and view all the answers

Which enzyme deficiency is commonly associated with hereditary nonspherocytic hemolytic anemia (HNSHA)?

Pyruvate Kinase Signup and view all the answers

Study Notes

Hemolytic Anemia

Hemolytic anemia (HA) is a heterogeneous group of conditions characterized by premature destruction of red blood cells (RBCs), or a shortened RBC lifespan.
Bone marrow (BM) can increase its output six to eight-fold to compensate for anemia. This corresponds to an RBC lifespan of 15-20 days.

Classification of Hemolytic Anemia

Intracorpuscular Defects: Inherited defects affecting the red blood cell (RBC) itself.
- Hereditary defects
  - Defects in the red blood cell membrane
  - Enzyme defects
  - Hemoglobinopathies
  - Thalassemia syndromes
- Acquired defects
  - Paroxysmal nocturnal hemoglobinuria (PNH)
Extracorpuscular Defects: Defects not intrinsic to the red blood cell, affecting the red cell exterior.
- Immune hemolytic anemia
- Infections
- Exposure to chemicals and toxins
- Exposure to physical agents
- Microangiopathic and macroangiopathic hemolytic anemias
- Splenic sequestration (hypersplenism)
- General systemic disorders (in which hemolysis is not the dominant feature of the anemia)

Diagnosis of Hemolytic Anemia

Tests reflecting increased red blood cell destruction:
- Serum unconjugated (indirect) bilirubin
- Hemoglobinemia
- Hemoglobinuria (dark urine)
- Hemosiderinuria (iron storage protein in urine)
- Methemalbumin in the blood (Schumm's test)
- Methemoglobinemia
- Serum Hemopexin
- Serum Haptoglobin
- Urine urobilinogen and fecal stercobilinogen increased

Degradation of Hb After Intra- & Extra-vascular Hemolysis

When present in high quantities, methemalbumin and hemopexin-heme complex impart a brownish colour to plasma.
Diagrammatic representation of hemoglobin degradation after intravascular or extravascular destruction of red blood cells.
Progressive urine samples in acute intravascular hemolysis showing hemoglobinuria of decreasing severity.

Tests Reflecting Increased Red Cell Production

Reticulocyte count
Reticulocyte production index (RPI)
RPI >2.5-3.0 is indicative of hemolytic anemia
Bone marrow (BM) erythroid hyperplasia; M:E ratio from 3-4:1 reduced to 1:1 or even reversed

Red Cell Membrane Structure

Red blood cell deformability is determined by the biconcave disc shape and the surface area-to-volume ratio (SA:Volume).
Cytoplasmic viscosity, determined by mean corpuscular hemoglobin concentration (MCHC).
Viscoelastic properties depend on the integrity of the membrane skeleton.
Diagrammatic illustrations of the red blood cell membrane skeleton network.
Table of integral and peripheral proteins involved.

Hereditary Defects of the Red Cell Membrane

Mutations affecting the membrane are numerous.
Classifications into specific phenotypes:
- Hereditary spherocytosis (HS)
- Hereditary elliptocytosis (HE) & related disorders (e.g., hereditary pyropoikilocytosis or HPP and Southeast Asian ovalocytosis)
- Hereditary stomatocytosis
- Hereditary xerocytosis
- Hereditary acanthocytosis

Hereditary Defects of RBC Membrane - Specifics

Inheritance: Most are autosomal dominant.
Red Cell Membrane Protein Defects: Gene mutations cause protein deficiencies leading to altered RBC shape and function: spectrin, ankyrin, band 3, protein 4.2
Pathophysiology: Loss of surface area leads to spherocytes. Increased permeability to sodium.

Classification of RBC Membrane Defects

Mutations affect RBC membrane, impacting the red blood cell's phenotype.
Vertical and horizontal protein interactions within the RBC membrane dictate the cell's shape.

Hereditary Spherocytosis (HS)

Inheritance: Autosomal dominant.
Membrane Protein Defects: Protein deficiencies in spectrin, ankyrin, band 3, and protein 4.2 commonly implicated.
Pathophysiology: Loss of membrane surface area leads to spherocytosis. Increased permeability to sodium.
Clinical Manifestations: Jaundice, anemia, enlarged spleen (splenomegaly), aplastic and hemolytic crises. Potential for gallstones and leg ulcers.

Hereditary Elliptocytosis (HE)

Inheritance: Usually autosomal dominant.
Defects: Defects in spectrin dimerization.
Clinical Features: Often asymptomatic.
Types: Hereditary pyropoikilocytosis (HPP); spherocytic HE
**Southeast Asian ovalocytosis (SA0):**Oval-shaped cells

Hereditary Pyropoikilocytosis (HPP)

Features: Relatively rare with severe hemolysis; showing microspherocytes, micropoikilocytosis, and fragments (few elliptocytes).
Diagnosis: Heterozygotes frequently exhibit defective spectrin.

Spherocytic HE

A hybrid of HE and HS, exhibiting clinical courses similar to HS.

Hereditary Stomatocytosis (Hydrocytosis) & Hereditary Xerocytosis

Inheritance: Often AD (autosomal dominant) inheritance patterns.
Defects: Defects in sodium & potassium; causes abnormal membrane permeability, affecting swell/shrink characteristics
Etiology: Defects in Na+/K+ permeability in Hst, K+ permeability leading to dehydration in Hxe
Clinical Features: Often asymptomatic or mild hemolysis.

Hereditary Acanthocytosis (Abetalipoproteinemia)

Inheritance: Autosomal recessive.
Features: Mild anemia, steatorrhea, neurological problems, and retinal abnormalities. Acnthocytes (spiky red blood cells) compose 50-100% of erythrocytes. Abnormal plasma lipid levels, lacking serum B lipoprotein, required for lipid transport.
Diagnostic features: Increased cholesterol: lecithin ratio in the membrane.

RBC Metabolic Pathway Disorders

Components of glycolytic pathway: Main glycolytic pathway and three ancillary pathways.
Specific enzymopathies: Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency and Pyruvate Kinase (PK) deficiency.

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

Inheritance: Sex-linked.
Defect: Deficiency in the enzyme leads to reduced glutathione levels. This leads to methemoglobin (Fe3+) formation.
Clinical Findings: The majority of patients are asymptomatic. Oxidant stress (drugs, infections, fava beans) trigger hemolysis (Favism).
Diagnosis: Decreased G6PD activity.
Variants: Gd B (normal), Gd Med, GdA+(normal), GdA-, Gd Canton

Pyruvate Kinase (PK) Deficiency

Inheritance: Autosomal recessive.
Defect: Lack of ATP (adenosine triphosphate) due to PK deficiency affects cation pumps, impairing intracellular sodium and potassium concentrations.
Clinical Course: Decreased erythrocyte deformability shortens RBC lifespan. Severe hemolytic anemia with reticulocytosis, and echinocytes
Diagnosis: Blood film; moderate increase in serum unconjugated bilirubin; quantitative PK assay; Osmotic fragility; Coombs test

Methemoglobin Reductase Deficiency

Inheritance: AR (autosomal recessive).
Diagnosis: Deficiency in the reductase enzyme responsible for converting methemoglobin (Fe3+) to hemoglobin (Fe2+) through a diagnostic enzyme assay.
Deficiency causes: Methemoglobinemia (cyanosis).

Assessment Questions

Q1: Common characteristics of hereditary spherocytosis, hereditary elliptocytosis, hereditary stomatocytosis, and paroxysmal nocturnal hemoglobinuria.
Q2: Least likely situations for hemolytic episodes in patients with G6PD deficiency.
Q3: Most likely condition causing a severe hemolytic episode after exposure to anti-malarials inducing red cell inclusions formed by denatured globin.
Q4: Characteristic defect in hereditary pyropoikilocytosis.
Q5: Reason for hemolytic crisis following primaquine drug exposure in a 32-year-old African American male.
Detailed patient information required for accurate differential diagnosis.

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Description

Test your knowledge on hereditary blood disorders such as hereditary pyropoikilocytosis, Southeast Asian ovalocytosis, and hereditary elliptocytosis. This quiz covers characteristic lab findings, red blood cell morphology changes, and associated defects. Perfect for students and professionals in hematology.