Hemolytic Anemia Part 2

*Question: In secondary hemolytic anemia, is hemolysis the primary cause?
A) Yes
B) No, there is another underlying condition
C) Sometimes
D) Only in acute cases

*Answer: B) No, there is another underlying condition

*Question: What is an example of secondary hemolytic anemia?
A) Hereditary spherocytosis
B) Iron deficiency anemia with secondary hemolysis
C) G6PD deficiency
D) PNH

*Answer: B) Iron deficiency anemia with secondary hemolysis

*Question: What causes acute renal failure in severe acute hemolysis?
A) Volume depletion
B) Heme toxicity causing flank pain, oliguria, anuria
C) Infection
D) Electrolyte imbalance

*Answer: B) Heme toxicity causing flank pain, oliguria, anuria

*Question: What is oliguria?
A) No urine output
B) Decreased urine output
C) Blood in urine
D) Protein in urine

*Answer: B) Decreased urine output

*Question: What is anuria?
A) Decreased urine output
B) No urine output
C) Blood in urine
D) Dark urine

*Answer: B) No urine output

*Question: What clinical symptoms may mimic infection in acute hemolytic anemia?
A) Shortness of breath
B) Malaise, aches, vomiting, fever
C) Chest pain
D) Confusion only

*Answer: B) Malaise, aches, vomiting, fever

*Question: What causes profound prostration and shock in acute fragmentation hemolysis?
A) Blood loss
B) Severe RBC destruction and hemoglobin release
C) Dehydration
D) Infection

*Answer: B) Severe RBC destruction and hemoglobin release

*Question: What is methemoglobinuria associated with?
A) Clear urine
B) Brown urine
C) Yellow urine
D) Green urine

*Answer: B) Brown urine

*Question: When is albumin used as a hemoglobin scavenger?
A) First line of defense
B) Second line of defense
C) Third line of defense when haptoglobin and hemopexin are saturated
D) Never used

*Answer: C) Third line of defense when haptoglobin and hemopexin are saturated

*Question: What forms when free hemoglobin is oxidized?
A) Biliverdin
B) Methemoglobin
C) Bilirubin
D) Haptoglobin

*Answer: B) Methemoglobin

*Question: What protein can temporarily bind metheme before it transfers to hemopexin?
A) Transferrin
B) Haptoglobin
C) Albumin forming metheme-albumin
D) Ferritin

*Answer: C) Albumin forming metheme-albumin

*Question: What is the GPI anchor composed of?
A) Proteins only
B) Phosphatidylinositol (PI) and glycan core
C) Lipids only
D) Carbohydrates only

*Answer: B) Phosphatidylinositol (PI) and glycan core

*Question: Where is phosphatidylinositol (PI) incorporated?
A) Inner leaflet of lipid bilayer
B) Outer leaflet of lipid bilayer membrane
C) Cytoplasm
D) Nucleus

*Answer: B) Outer leaflet of lipid bilayer membrane

*Question: What enzyme complex is encoded by the PIGA gene?
A) Heme oxygenase
B) Glycosyl transferase enzyme
C) Biliverdin reductase
D) Lactate dehydrogenase

*Answer: B) Glycosyl transferase enzyme

*Question: What is the first step in GPI anchor biosynthesis?
A) Adding iron to protoporphyrin
B) Adding N-acetylglucosamine to PI
C) Adding glucose to hemoglobin
D) Adding heme to globin

*Answer: B) Adding N-acetylglucosamine to PI

*Question: What are GPI-anchored proteins?
A) Only complement regulators
B) Complement regulators, enzymes, adhesion molecules, blood group antigens, receptors
C) Only enzymes
D) Only blood group antigens

*Answer: B) Complement regulators, enzymes, adhesion molecules, blood group antigens, receptors

*Question: What is DAF?
A) Direct Antiglobulin Factor
B) Decay Accelerating Factor (CD55)
C) Deficient Antigen Formation
D) Damaged Abnormal Fragments

*Answer: B) Decay Accelerating Factor (CD55)

*Question: What is MIRL?
A) Membrane Induced Red Lysis
B) Membrane Inhibitor of Reactive Lysis (CD59)
C) Membrane Integrated Receptor Ligand
D) Macrophage Induced RBC Lysis

*Answer: B) Membrane Inhibitor of Reactive Lysis (CD59)

*Question: Why do both males and females express PNH phenotype despite PIGA being X-linked?
A) It's autosomal, not X-linked
B) Males have only 1 X, females have X-inactivation (lyonization)
C) Gene is on both X and Y
D) Mutation occurs after fertilization

*Answer: B) Males have only 1 X, females have X-inactivation (lyonization)

*Question: What is phenotypic mosaicism in PNH?
A) All cells are identical
B) Patient harbors normal and mutant clones with different PIGA mutations
C) Only Type I cells present
D) Only Type III cells present

*Answer: B) Patient harbors normal and mutant clones with different PIGA mutations

*Question: What characterizes Type I PNH cells?
A) Complete absence of GPI anchors
B) Phenotypically normal with little to no complement lysis
C) Severe complement lysis
D) No CD55 or CD59

*Answer: B) Phenotypically normal with little to no complement lysis

*Question: What characterizes Type II PNH cells?
A) Normal cells
B) PIGA mutation causing deficiency, relatively resistant to complement lysis
C) Complete absence of CD55/CD59 with spontaneous lysis
D) No mutation present

*Answer: B) PIGA mutation causing deficiency, relatively resistant to complement lysis

*Question: What characterizes Type III PNH cells?
A) Normal cells
B) Resistant to lysis
C) PIGA mutation causing no CD55/CD59 with spontaneous complement lysis
D) Mild deficiency only

*Answer: C) PIGA mutation causing no CD55/CD59 with spontaneous complement lysis

*Question: What is the most common PNH phenotype combination?
A) Only Type I cells
B) Type I and Type III cells
C) Only Type II cells
D) Only Type III cells

*Answer: B) Type I and Type III cells

*Question: What is the second most common PNH phenotype pattern?
A) Type I only
B) Type III only
C) All three types (I, II, and III) present
D) Type II and III only

*Answer: C) All three types (I, II, and III) present

*Question: In which decade of life does PNH most commonly occur?
A) 1st or 2nd decade
B) 3rd or 4th decade
C) 5th or 6th decade
D) 7th or 8th decade

*Answer: B) 3rd or 4th decade

*Question: What are the three major complications of PNH?
A) Infection, bleeding, anemia
B) Hemolytic anemia, thrombosis, bone marrow failure
C) Kidney failure, heart failure, liver failure
D) Stroke, MI, PE only

*Answer: B) Hemolytic anemia, thrombosis, bone marrow failure

*Question: Why does smooth muscle dystonia occur in PNH?
A) Direct RBC damage to muscles
B) Nitric oxide depletion from free hemoglobin binding
C) Antibody attack on smooth muscle
D) Calcium imbalance

*Answer: B) Nitric oxide depletion from free hemoglobin binding

*Question: What GI symptom is common in PNH due to smooth muscle dystonia?
A) Diarrhea
B) Constipation
C) Dysphagia (difficulty swallowing)
D) Vomiting only

*Answer: C) Dysphagia (difficulty swallowing)

*Question: What causes erectile dysfunction in male PNH patients?
A) Low testosterone
B) Inability for vasodilation due to nitric oxide depletion
C) Thrombosis only
D) Psychological factors

*Answer: B) Inability for vasodilation due to nitric oxide depletion

*Question: What is Budd-Chiari syndrome?
A) Kidney vein thrombosis
B) Blood clots in liver veins obstructing blood flow
C) Lung vein thrombosis
D) Brain vein thrombosis

*Answer: B) Blood clots in liver veins obstructing blood flow

*Question: What causes chronic renal disease in PNH?
A) Dehydration
B) Renal tubular damage from microvascular thrombosis and iron accumulation
C) Infection
D) Hypertension only

*Answer: B) Renal tubular damage from microvascular thrombosis and iron accumulation

*Question: What is the annual incidence of PNH in the US?
A) 1 case per million
B) 2-5 new cases per million
C) 10-15 cases per million
D) 20-30 cases per million

*Answer: B) 2-5 new cases per million

*Question: What characterizes classic PNH?
A) No hemolysis
B) Clinical and biochemical evidence of intravascular hemolysis with reticulocytosis
C) Only bone marrow failure
D) Extravascular hemolysis only

*Answer: B) Clinical and biochemical evidence of intravascular hemolysis with reticulocytosis

*Question: What percentage of neutrophils are GPI-deficient in hypoplastic PNH?
A)

*Answer: C) 20-30%

*Question: What defines subclinical PNH?
A) Severe hemolysis
B) No clinical or biochemical evidence of hemolysis with small GPI-deficient population
C) Thrombosis only
D) Bone marrow failure only

*Answer: B) No clinical or biochemical evidence of hemolysis with small GPI-deficient population

*Question: What percentage of neutrophils are GPI-deficient in subclinical PNH?
A)

*Answer: A) <1%

*Question: What lab finding indicates increased plasma hemoglobin in PNH?
A) Decreased LDH
B) Increased serum haptoglobin
C) Decreased serum haptoglobin
D) Normal bilirubin

*Answer: C) Decreased serum haptoglobin

*Question: What happens to LDH in PNH?
A) Decreased
B) Increased
C) No change
D) Variable

*Answer: B) Increased

*Question: What happens to indirect bilirubin in PNH?
A) Decreased
B) No change
C) Increased
D) Becomes conjugated

*Answer: C) Increased

*Question: Is Eculizumab curative for PNH?
A) Yes, completely curative
B) No, does not address bone marrow failure complications
C) Only for acute cases
D) Only for chronic cases

*Answer: B) No, does not address bone marrow failure complications

*Question: What supportive treatments are used in PNH?
A) Antibiotics only
B) Iron therapy, folate, androgens, glucocorticoids, anticoagulants
C) Chemotherapy
D) Radiation

*Answer: B) Iron therapy, folate, androgens, glucocorticoids, anticoagulants

*Question: Why are anticoagulants given in PNH?
A) To treat anemia
B) To prevent thrombosis
C) To increase hemoglobin
D) To cure the disease

*Answer: B) To prevent thrombosis

*Question: What is the membrane attack complex (MAC)?
A) Antibody complex
B) Terminal complement complex (C5b-9) that lyses cells
C) Protein complex that protects cells
D) Enzyme complex

*Answer: B) Terminal complement complex (C5b-9) that lyses cells

*Question: What does CD163 bind to?
A) Free hemoglobin
B) Hemoglobin-haptoglobin complex
C) Hemopexin-heme complex
D) Free heme

*Answer: B) Hemoglobin-haptoglobin complex

*Question: Where is CD163 found?
A) Hepatocytes
B) RBCs
C) Macrophages
D) Neutrophils

*Answer: C) Macrophages

*Question: Where is CD91 found?
A) Macrophages
B) Hepatocytes
C) RBCs
D) Platelets

*Answer: B) Hepatocytes

*Question: What happens to globin chains after hemoglobin breakdown?
A) Excreted in urine
B) Broken down to amino acids and recycled for protein synthesis
C) Stored in liver
D) Eliminated in feces

*Answer: B) Broken down to amino acids and recycled for protein synthesis

*Question: What happens to the protoporphyrin ring after heme breakdown?
A) Recycled as hemoglobin
B) Converted to unconjugated bilirubin
C) Excreted unchanged
D) Stored as ferritin

*Answer: B) Converted to unconjugated bilirubin

*Question: Where does conjugation of bilirubin occur?
A) Spleen
B) Smooth endoplasmic reticulum of hepatocytes
C) Bone marrow
D) Kidneys

*Answer: B) Smooth endoplasmic reticulum of hepatocytes

*Question: What carries unconjugated bilirubin to hepatocytes?
A) Ligandin
B) Y and Z proteins
C) Albumin
D) Transferrin

*Answer: C) Albumin

*Question: What protein carries bilirubin inside the hepatocyte to smooth ER?
A) Albumin
B) Ligandin
C) Transferrin
D) Hemopexin

*Answer: B) Ligandin

*Question: What is another name for conjugated bilirubin?
A) Indirect bilirubin
B) Bilirubin diglucuronide
C) Free bilirubin
D) Unconjugated bilirubin

*Answer: B) Bilirubin diglucuronide

*Question: Where is conjugated bilirubin excreted?
A) Urine directly
B) Small intestine via bile
C) Kidneys
D) Lungs

*Answer: B) Small intestine via bile

*Question: What converts conjugated bilirubin to urobilinogen?
A) Liver enzymes
B) Kidney enzymes
C) Intestinal bacteria
D) Pancreatic enzymes

*Answer: C) Intestinal bacteria

*Question: What is the major pigment giving urine its yellow color?
A) Urobilin
B) Bilirubin
C) Urochrome
D) Stercobilin

*Answer: C) Urochrome

*Question: What happens to some urobilinogen from the intestine?
A) All excreted in feces
B) Some reabsorbed into portal and systemic circulation
C) All excreted in urine
D) Stored in liver

*Answer: B) Some reabsorbed into portal and systemic circulation

*Question: What circulation does reabsorbed urobilinogen enter to return to the liver?
A) Systemic circulation
B) Pulmonary circulation
C) Extrahepatic (enterohepatic) circulation
D) Coronary circulation

*Answer: C) Extrahepatic (enterohepatic) circulation

*Question: What is the normal direct (conjugated) serum bilirubin level?
A) 0-0.2 mg/dL
B) 0.5-1.0 mg/dL
C) 1.0-2.0 mg/dL
D) 2.0-3.0 mg/dL

*Answer: A) 0-0.2 mg/dL

*Question: What is the normal indirect (unconjugated) serum bilirubin level?
A) 0-0.2 mg/dL
B) 0-0.8 mg/dL
C) 1.0-2.0 mg/dL
D) 2.0-3.0 mg/dL

*Answer: B) 0-0.8 mg/dL

*Question: What recognizes aged RBCs for removal?
A) Neutrophils
B) Macrophages in reticuloendothelial system
C) Lymphocytes
D) Platelets

*Answer: B) Macrophages in reticuloendothelial system

*Question: Where are macrophages of the reticuloendothelial system located?
A) Only in spleen
B) Liver, spleen, bone marrow, lymph nodes; monocytes in blood
C) Only in liver
D) Only in bone marrow

*Answer: B) Liver, spleen, bone marrow, lymph nodes; monocytes in blood

*Question: What is icterus?
A) Yellow coloring of plasma and tissues
B) Yellow coloring of urine only
C) Red coloring of skin
D) Blue coloring of skin

*Answer: A) Yellow coloring of plasma and tissues

*Question: Why can unconjugated bilirubin deposit in brain tissue?
A) Water solubility
B) Lipid solubility
C) Protein binding
D) Large molecular size

*Answer: B) Lipid solubility

*Question: What must be ruled out when establishing hemolytic anemia?
A) Infection only
B) Hemorrhage and hemodilution
C) Dehydration only
D) Malnutrition only

*Answer: B) Hemorrhage and hemodilution

*Question: What rate of hemoglobin decrease suggests hemolytic anemia?
A) 0.5 g/dL/week
B) 1 g/dL/week
C) 2 g/dL/week
D) 5 g/dL/week

*Answer: B) 1 g/dL/week

*Question: What happens to reticulocyte count in hemolytic anemia?
A) Decreased
B) Increased (reticulocytosis)
C) No change
D) Becomes zero

*Answer: B) Increased (reticulocytosis)

*Question: What is the color of plasma in severe fragmentation hemolysis?
A) Clear yellow
B) Coffee-brown
C) Green
D) White

*Answer: B) Coffee-brown

*Question: What is the color of urine in severe fragmentation hemolysis?
A) Clear yellow
B) Root beer or beer-colored
C) Green
D) Colorless

*Answer: B) Root beer or beer-colored

*Question: What components cause coffee-brown plasma color in hemolysis?
A) Bilirubin only
B) Methemoglobin, methemalbumin, hemopexin-heme complexes
C) Urobilin
D) Conjugated bilirubin

*Answer: B) Methemoglobin, methemalbumin, hemopexin-heme complexes

*Question: What test can be positive in urine even without visible color change in hemolysis?
A) Glucose test
B) Protein test
C) Blood test strip
D) Ketone test

*Answer: C) Blood test strip

*Question: What will urine sediment show for RBCs in hemoglobinuria?
A) Many RBCs
B) Few RBCs
C) Negative for RBCs
D) Clumped RBCs

*Answer: C) Negative for RBCs

*Question: What suggests fragmentation hemolysis is occurring?
A) Absence of hemoglobinemia and hemoglobinuria
B) Presence of hemoglobinemia and hemoglobinuria
C) Low bilirubin
D) Normal haptoglobin

*Answer: B) Presence of hemoglobinemia and hemoglobinuria

*Question: What happens to haptoglobin in macrophage-mediated hemolysis?
A) Increased
B) Moderately decreased
C) Severely decreased
D) No change

*Answer: B) Moderately decreased

*Question: Why is haptoglobin moderately decreased in macrophage-mediated hemolysis?
A) Major component of extravascular lysis
B) Minor component of fragmentation in spherical cells
C) Not involved
D) Increased consumption

*Answer: B) Minor component of fragmentation in spherical cells

*Question: When might haptoglobin be normal despite hemolysis?
A) In severe hemolysis
B) When infection/inflammation is present (acute phase reactant)
C) In chronic hemolysis
D) Never

*Answer: B) When infection/inflammation is present (acute phase reactant)

*Question: Is hemopexin commonly measured in clinical practice?
A) Yes, routinely measured
B) No, not often measured
C) Always measured
D) Only in PNH

*Answer: B) No, not often measured

*Question: When is hemopexin measurement valuable?
A) In all hemolytic anemias
B) For detection of depletion in sepsis
C) Only in acute hemolysis
D) Never useful

*Answer: B) For detection of depletion in sepsis

*Question: Where is carbon monoxide produced during hemolysis?
A) In the kidney
B) In the first step of heme breakdown by heme oxygenase
C) In the spleen only
D) In bone marrow only

*Answer: B) In the first step of heme breakdown by heme oxygenase

*Question: What indicates mild hemolysis in Chromium-51 RBC survival studies?
A) Half-time 25-32 days
B) Half-time 20-25 days
C) Half-time 15-20 days
D) Half-time <15 days

*Answer: B) Half-time 20-25 days

*Question: What indicates moderate hemolysis in Chromium-51 RBC survival studies?
A) Half-time 25-32 days
B) Half-time 20-25 days
C) Half-time 15-20 days
D) Half-time <15 days

*Answer: C) Half-time 15-20 days

*Question: Why is Chromium-51 testing limited to research?
A) Not accurate
B) Time consuming and expensive
C) Not available
D) Too simple

*Answer: B) Time consuming and expensive

*Question: What is problematic about using HbA1c to assess hemolysis?
A) Always inaccurate
B) Problematic without baseline; falsely low in DM with hemolysis
C) Too expensive
D) Not sensitive

*Answer: B) Problematic without baseline; falsely low in DM with hemolysis

*Question: What happens to white blood cell count in hemolytic anemia?
A) Always decreased
B) May be increased
C) Always normal
D) Always severely decreased

*Answer: B) May be increased

*Question: What happens to platelet count in hemolytic anemia?
A) Always increased
B) May be decreased
C) Always normal
D) Always severely increased

*Answer: B) May be decreased

*Question: What cells may be seen in blood film indicating increased erythropoiesis?
A) Schistocytes only
B) Nucleated RBCs and polychromatic RBCs
C) Target cells only
D) Acanthocytes only

*Answer: B) Nucleated RBCs and polychromatic RBCs

*Question: What test identifies specific types of RBC enzyme deficiencies?
A) CBC
B) RBC enzyme studies
C) Bilirubin test
D) Reticulocyte count

*Answer: B) RBC enzyme studies

*Question: What test uses flow cytometry to detect GPI-deficient cells in PNH?
A) Osmotic fragility
B) Direct Antiglobulin test
C) Immunophenotyping
D) Hemoglobin electrophoresis

*Answer: C) Immunophenotyping

*Question: What is the purpose of the Direct Antiglobulin Test (DAT)?
A) Detect enzyme deficiencies
B) Detect antibodies on RBC surface (autoimmune hemolytic anemia)
C) Detect hemoglobin variants
D) Measure bilirubin

*Answer: B) Detect antibodies on RBC surface (autoimmune hemolytic anemia)

*Question: What confirms persistent chronic hemolysis?
A) Single episode of hemoglobinuria
B) Persistent hemoglobinemia, hemoglobinuria, decreased haptoglobin, reticulocytosis
C) One elevated bilirubin
D) Normal CBC

*Answer: B) Persistent hemoglobinemia, hemoglobinuria, decreased haptoglobin, reticulocytosis

*Question: What type of hemolysis occurs with no free hemoglobin in plasma?
A) Intravascular hemolysis
B) Extravascular (macrophage-mediated) hemolysis
C) Fragmentation hemolysis
D) Acute hemolysis

*Answer: B) Extravascular (macrophage-mediated) hemolysis

*Question: Why is there no hemoglobinemia in extravascular hemolysis?
A) RBCs not destroyed
B) RBC contents degraded inside macrophages, not released to plasma
C) Hemoglobin converted immediately
D) Kidneys filter it quickly

*Answer: B) RBC contents degraded inside macrophages, not released to plasm