Exam 4 Material Flashcards by Nicolas Golder

Define the following:

Aplastic Anemia

Aplastic Anemia: disorder characterized by cellular depletion and fatty replacement of the BM

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Aplastic Anemia –

a. Most common cause

b. Five (5) secondary causes

c. Name of most common congenital disorder associated with aplastic anemia

a. Idiopathic – cause unknown

b.
1. Chemicals
2. Drugs
3. Radiation
4. Infections, esp. chronic
5. Myelophthistic replacement

c. Fanconi’s anemia

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Aplastic anemia –

a. BM cellularity

b. Characteristic RBC morphology

c. Reticulocyte count

a. Hypocellular – upon BM aspiration, could have a “dry tap” (no cells aspirated)

b. Normocytic-Normochromic

c. Decreased to absent

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Aplastic anemia –

a. CBC results

a. Mkd. decrease WBC count (< 1.5)
Mkd. decrease RBC count
Mkd. decrease Hgb. (< 7g/dL)
Mkd. decrease Plt. Count (20-60,000 cumm)

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Aplastic anemia –

a. Treatment

a. Eliminate offending agent, if possible
“Support” therapy
• Antibiotics
• Blood products, esp. platelets and/or PRBCs
• Use of growth factors
Immunosuppressive therapy
Bone Marrow transplant

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Define:

Hemoglobinopathy

Hemoglobinopathy: defect in the globin chain structure – typically a single point mutation that has altered the shape/structure/property of the globin chain (beta chain is most commonly affected)

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Name the type of poikilocytosis that is found in most every hemoglobinopathy.

Target cells

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Name the amino acid substitution found in sickle cell anemia.

On the beta chain, at the sixth (6th) position, glutamic acid is replaced by valine

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List three factors contributing to the sickling process.

Hypoxia – decrease of oxygen to the tissues
Acidosis – decrease in pH
Dehydration – decrease in plasma volume

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Discuss the cause for each of the following clinical features of sickle cell anemia:

“Painful crises”:

“Acute chest syndrome”:

High risk of infections:

“Painful crises”: tissue damage precipitated by infection, fever, dehydration, exposure to extreme cold

“Acute chest syndrome”: pulmonary infarction – obstruction of blood flow, leading to tissue death due to lack of oxygen – can virtually occur in any organ (i.e. autosplenectomy – spleen becomes nonfunctional)

High risk of infections: spleen can’t aide in infections, due to the infarctions, resulting in decrease function and increase in infections

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Compare and contrast sickle cell anemia and sickle cell trait according to:

Inheritance
Hgb. nomenclature
Solubility results
Hgb. Electrophoresis results
RBC morphology
Tx.

Inheritance
Sickle cell anemia:
Sickle cell trait:

Hgb. nomenclature
Sickle cell anemia: SS
Sickle cell trait: AS

Solubility results
Sickle cell anemia: Positive
Sickle cell trait: Positive

Hgb. Electrophoresis results
Sickle cell anemia: Migration to S and F – S > F (no A)
Sickle cell trait: Migration to S & A — A > S

RBC morphology
Sickle cell anemia: Targets + sickles, schistos, spheres, poly, H-J, Pap
Sickle cell trait: Slt. Targets, no sickles

Tx.
Sickle cell anemia: Adequate hydration, Pain relief (morphine), Antibiotics, Blood transfusion, Hydroxyurea to increase Hgb F, BM transplant, CRISPR

Sickle cell trait: No treatment

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Discuss the Sickledex solubility (screening) test, including the:

Principle:

Reducing agent:

Causes for false positive results:

Causes for false negative results:

Principle: qualitative screening test for the presence of Hgb S – unable to differentiate sickle cell trait and sickle cell anemia

Reducing agent: sodium dithionite or sodium metabisulfite

Causes for false positive results:

• Proteinemia
• >18 g/dL HGB
• Other sickling HGBs

Causes for false negative results:

• Testing a newborn – the gamma-beta switch has not quite occurred; therefore, not enough Hgb S is present to be detectable
• < 7 g/dL HGB
• Multiple transfusions

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Name the amino acid substitution found in Hemoglobin C disease.

On the beta chain, at the sixth (6th) position, glutamic acid is replaced by lysine

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Compare and contrast Hemoglobin C disease and Hemoglobin C trait according to:

Clinical presentation
Hemoglobin nomenclature (AC versus CC)
Hemoglobin electrophoresis results
RBC morphology

Clinical presentation
Hemoglobin C disease: Mild hemolytic anemia, Splenomegaly
Hemoglobin C trait: Asymptomatic

Hemoglobin nomenclature (AC versus CC)
Hemoglobin C disease: CC
Hemoglobin C trait: AC

Hemoglobin electrophoresis results
Hemoglobin C disease: 100% C (no A)
Hemoglobin C trait: A > C

RBC morphology
Hemoglobin C disease: Targets + C crystals, poly
Hemoglobin C trait: Targets ONLY

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Discuss Hemoglobin SC Disease according to:

Inheritance:

Clinical presentation:

Hemoglobin electrophoresis results:

RBC morphology:

Inheritance: Lysine substitution (C) from one parent – valine substitution (S) from the other parent

Clinical presentation: mild to moderately hemolytic anemia with painful crises

Hemoglobin electrophoresis results: S=C

RBC morphology: Targets + sickles, C crystals, S-C crystals, poly, H-J, Papp, nRBCs

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Interpret cellulose acetate hemoglobin electrophoresis patterns for the following conditions:

cord blood
hemoglobin C disease
hemoglobin C trait
hemoglobin SC disease
sickle cell disease
sickle cell trait

Review electrophoresis slides for this information

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Discuss Sickle Cell-Beta Thal according to:

Inheritance
Clinical presentation (Sickle-Beta0 Thal versus Sickle-Beta+ Thal)
Hemoglobin electrophoresis results (Sickle-Beta0 Thal versus Sickle-Beta+ Thal)
RBC morphology (Sickle-Beta0 Thal versus Sickle-Beta+ Thal)

Inheritance
Sickle-Beta0 Thal: Valine substitution (S) from one parent – B0 from the other parent
Sickle-Beta+ Thal: Valine substitution (S) from one parent – B+ from the other parent

Clinical presentation (Sickle-Beta0 Thal versus Sickle-Beta+ Thal)
Sickle-Beta0 Thal: Severe hemolytic anemia
Sickle-Beta+ Thal: Mild to Moderate anemia

Hemoglobin electrophoresis results (Sickle-Beta0 Thal versus Sickle-Beta+ Thal)
Sickle-Beta0 Thal: S > F > A2 (w/ no A)
Sickle-Beta+ Thal: S > A > F > A2

RBC morphology (Sickle-Beta0 Thal versus Sickle-Beta+ Thal)
Sickle-Beta0 Thal: Targets + sickles (usually), schistos, spheres, poly, H-J, Papp, nRBCs!!!
Sickle-Beta+ Thal: Same as Sickle-Beta0 Thal

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List two ways that Hemoglobin D may be differentiated from Hemoglobin S … since they both migrate to the same point on cellulose acetate electrophoresis.

Solubility testing (negative)
Citrate acid electrophoresis

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State the world’s third most common abnormal hemoglobin (behind Hgb S and Hgb C) and indicate the geographic area in which it commonly occurs.

Hemoglobin E – common in SE Asia

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State the physiological mechanism for the predominant type of poikilocytosis found in the following hereditary hemolytic anemias:

Hereditary spherocytosis:

Hereditary elliptocytosis:

Hereditary stomatocytosis:

Hereditary spherocytosis: Decreased spectrin causes increased permeability of sodium into cell

Hereditary elliptocytosis: Decreased cholesterol in cell membrane causes hemoglobin to polarize to opposite ends – forming elliptocytes

Hereditary stomatocytosis: Defect in the sodium-potassium pump: results in abnormal slit-like pallor

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Discuss Hereditary Spherocytosis according to:

Clinical presentation:

RBC indices:

RBC morphology:

Clinical presentation:
• Anemia
• Jaundice
• Splenomegaly

RBC indices:
• Hgb ~ 12g/dL
• MCV: normal
• MCHC: 36-38%

RBC morphology:
• Variable # of spheres
• Polychromasia

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Discuss the osmotic fragility test with regard to:

Principle:

Conditions that show “increased osmotic fragility”:

Conditions that show “decreased osmotic fragility”:

Conditions that show “decreased resistance to hemolysis”:

Conditions that show “increased resistance to hemolysis”:

NaCl concentration when hemolysis should begin (in a normal person):

NaCl concentration when hemolysis should be completed (in a normal person):

Principle: A test to display the tendency of RBCs to break apart by adding them to a series of hypotonic salt solutions

Conditions that show “increased osmotic fragility”
Heredity spherocytosis

Conditions that show “decreased osmotic fragility”:
Hypochomic anemia
Sickle cell anemia
Any disease/condition with targets
Thalassemia

Conditions that show “decreased resistance to hemolysis”:
Heredity spherocytosis

Conditions that show “increased resistance to hemolysis”:
Hypochomic anemia
Sickle cell anemia
Any disease/condition with targets
Thalassemia

NaCl concentration when hemolysis should begin (in a normal person):
~ 0.45 – 0.50% NaCl

NaCl concentration when hemolysis should be completed (in a normal person):
~ 0.30 – 0.35% NaCl

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State the type of poikilocytosis that demonstrates the greatest resistance to hemolysis.

Hypochomic anemia
Sickle cell anemia
Any disease/condition with targets
Thalassemia

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State the expected results that occur with any hemolytic anemia for the following:

Plasma haptoglobin:

Reticulocyte count:

Serum bilirubin:

Plasma haptoglobin: Decreased

Reticulocyte count: Increased

Serum bilirubin: Increased

Discuss the following hereditary hemolytic anemias: 1) G-6-PD deficiency, 2) PK deficiency, and 3) Methemoglobin Reductase deficiency, ... according to: Result of deficient enzyme (include type of poik or inclusion bodies present)

Result of deficient enzyme (include type of poik or inclusion bodies present) according to: 1) G-6-PD deficiency: Mkd. decrease in RBC count Hemoglobinemia Hematuria Heinz bodies Bite cells 2) PK deficiency: Burr cells 3) Methemoglobin Reductase deficiency: Generally – benign, enough normal Hgb is made, if severe, people become cyanotic

Triggering factors in G-6-PD Deficiency

• Administration of a new drug • Infection • Ingestion of fava beans or moth balls

Discuss Paroxysmal Nocturnal Hemoglobinuria (PNH) according to: Etiology: Clinical presentation: CBC: RBC morphology: Ham's Test results:

Etiology: Abnormality in hematopoietic cell membrane Clinical presentation: Sleep-induced hemolytic anemia – bloody first morning urine – urine clears throughout the day CBC Pancytopenia (the loss of ALL blood cell lines) – decreased RBCs, WBCs, and Plts RBC morphology No unusual RBC morphology Ham's Test results Positive

State the principle of the Ham's Test.

To test for the presence of PNH cells – due to an intrinsic membrane defect, they are more sensitive to lysis by complement – serum is acidified and maintain at 37 deg C for optimal C’ activation

List three conditions that may cause an alloimmune hemolytic anemia to develop.

1. Transfusion 2. Pregnancy 3. Organ Transplantation

Differentiate an autoimmune hemolytic anemia from an alloimmune hemolytic anemia.

Autoimmune hemolytic anemia: the ability of self-recognition is lost – antibodies are directed against our own RBCs Alloimmune hemolytic anemia: the production of antibodies to foreign RBC antigens

Discuss a cold agglutinin according to: Alloimmune versus autoimmune etiology? CBC results RBC morphology

Alloimmune versus autoimmune etiology?: Autoimmune CBC results: Very decreased RBC count Very increased MCV, MCHC, RDW Rule of 3 is not followed RBC morphology: RBC agglutination

State the antibody associated with Paroxysmal Cold Hemoglobinuria.

IgG

List three disorders commonly associated with microangiopathic hemolytic anemia (MAHA).

1. Hemolytic uremic syndrome (HUS) 2. Thrombotic thrombocytopenic purpura (TTP) 3. Disseminated intravascular coagulation (DIC)

State the predominant type of poik found in MAHA patients.

Schistocytes

Define the following: Autosplenectomy

occurs when a disease damages the spleen to such an extent that it becomes shrunken and non-functional

Define the following: Microangiopathic hemolytic anemia (MAHA).

An intravascular hemolysis caused by excessive shear or turbulence in the circulation.

Define the following: Paroxysmal Cold Hemoglobinuria

An autoimmune hemolytic anemia caused by autoantibodies (i.e. IgG) at < 37° C.

Define the term "megaloblastic anemia" according to: Cellular component impaired (DNA or RNA?): Three general causes for this impairment:

Cellular component impaired (DNA or RNA?): DNA Three general causes for this impairment: 1. Deficiency of vitamin B12 2. Deficiency of folate 3. Drugs that interfere with DNA metabolism

Describe the typical megaloblastic changes in the erythrocyte, leukocyte, and platelet precursors in the bone marrow. Erythrocyte line: Leukocyte line: Platelet line:

Erythrocyte line: o Megaloblasts o Asynchronous maturation Leukocyte line: o Giant forms (metas, bands) o Asynchronous development Platelet line: o Abnormal – but not as distinctive

Describe the typical megaloblastic changes in the erythrocytes, leukocytes, and platelets found in the peripheral blood. Erythrocyte line: Leukocyte line: Platelet line:

Erythrocyte line: o Oval macrocytes o Teardrops o H-J bodies o Cabot Rings Leukocyte line: o Giant forms (metas, bands) o Hypersegmented neutrophils Platelet line: o May see giant platelets

Correlate the bone marrow findings in a megaloblastic anemia with the peripheral blood picture... including the cause of the following: Cabot rings: Decreased retic count: Howell-Jolly bodies: Hyperplastic BM - pancytopenic PB: Hypersegmented polys: Increased MCV: Macroovalocytes: Teardrop cells:

Cabot rings: increase it mitotic figures Decreased retic count: ineffective hematopoiesis Howell-Jolly bodies: fragmenting of the RBC nucleus Hyperplastic BM  pancytopenic PB: “hallmark of ineffective hematopoiesis” – increased RBC precursors in the BM with a decreased release into the PB Hypersegmented polys: fragmenting of the WBC nucleus Increased MCV: due to the presence of Macroovalocytes Macroovalocytes: due to asynchronous maturation Teardrop cells: due to the “squeezing” of these large cells in the microvascular of the spleen or endothelial sinusoid gaps in the BM

State the expected results you would find in a patient with a megaloblastic anemia for the following chemistry tests: Serum bilirubin: Serum LDH (lactate dehydrogenase): Serum iron:

Serum bilirubin: increased Serum LDH (lactate dehydrogenase): increased Serum iron: increased

Discuss Vitamin B12 absorption from the GI tract according to: Function of intrinsic factor (IF): Site of intrinsic factor production: Site of absorption:

Function of intrinsic factor (IF): binds to B12 allowing it to be absorbed Site of intrinsic factor production: parietal cells of the stomach Site of absorption: ileum

State the storage organ and extent of body stores for Vitamin B12.

Liver – storage rate is high (~4-5 yrs. To develop a deficiency)

Discuss the clinical features that deficiencies in Vitamin B12 and / or folate share.

• General signs of anemia (pallor, weakness, fatigue, SOB, etc.) • Sore tongue (“beefy red”) • “Lemon yellow” skin from jaundice

State which megaloblastic anemia is unique to neurological problems.

Vitamin B12 deficiency

State the most common cause of a Vitamin B12 deficiency.

Impaired absorption

Discuss the defect in pernicious anemia which leads to impaired Vitamin B12 absorption.

Inability of gastric mucosa to secrete intrinsic factor – autoimmune disorder

Explain the means by which a D. latum (parasite) or increased bacterial flora in the GI tract causes a Vitamin B12 deficiency.

These bacterium/parasite use B12 for their own growth – decreasing the availability of it for our absorption

Discuss folate metabolism according to: Site of absorption: Extent of body stores:

Site of absorption: jejunum Extent of body stores: Not as high as B12 – ~4-5 months storage

State the most common cause of a folic acid deficiency.

Poor diet

List four causes for an increased requirement of folic acid.

1. Accelerated hematopoiesis 2. Neoplastic disease 3. Growth 4. Pregnancy

Name three drugs that interfere with the absorption of folate.

1. Folate antagonists (i.e. chemotherapy) 2. Birth control pill 3. Dilantin

State the RBC morphology you would expect to see in a patient with a non-megaloblastic anemia.

• Round macrocytes • Targets • Stomatocytes • Spur cells

List two causes for a non-megaloblastic anemia.

1. Liver disease and/or alcoholism 2. Reticulocytosis

State the physiological reason for the presence of target cells in the peripheral blood of a patient with liver disease.

Increased plasma cholesterol leads to increased cholesterol in the RBC membrane

Define the following: asynchronous maturation

Defective DNA synthesis which causes nuclear maturation at a slower rate than the cytoplasm

Define the following: transcobalamin II

Responsible for delivering vitamin B12 to the tissues

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Exam 4 Material Flashcards

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