Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key


Play button


Play button




Click to flip

84 Cards in this Set

  • Front
  • Back
Define Hemoglobinopathy
STRUCTURAL defects in Hemoglobin resulting in an abnormal Hb molecule that can precipitate out/polymerize and lead to hemolysis
What is HbA?
Normal Hemoglobin with 2 Alpha & 2 Beta chains
What is HbA2?
Hb with 2 Alpha and 2 Delta chains
What is HbF?
Hb with 2 Alpha and 2 Gamma chains

Hemoglobin whose gene is on Chromosome 16

**you have 4 copies of Alpha genes
Hemoglobin whose gene is on Chromosome 11
Beta, Gamma, Delta

**have 2 copies of each
What is the abnormality in Sickle Cell Disease?
Point mutation in which Valine is substituted for Glutamate at position 6 of the BETA chain of Hemoglobin
Describe the Pathogenesis of Sickle Cell disease
1. Deoxygenation
2. Aggregation and polymerizatoin of HbS
3. Reversible sickling
4. Irreversible sickling
5. Hemolysis
What type of hereditary disease is Sickle Cell Disease?
Autosomal Recessive = must have both recessive alleles to be diseased = HbS/HbS
What group of people have 8% of their population with the Sickle Cell trait (heterozygous = carry trait but are asymptomatic)?
African Americans
Describe the polymerization of Hb in Sickle Cell Disease
HbS polymerize only with other HbS and do so only in the Deoxy state
What conditions make Sickle Cell Disease worse?
1. Dehydration = increased concentration of RBC's with HbS
2. Low pH (acidic) = decreases Oxygen affinity for RBC --> causes Deoxy
Describe the Sickle Cell Trait
Patients are Heterozygotes and only a portion of the hemoglobin is HbS and the remainder is normal HbA. RBC sickling and possibly hemolysis occur in hypoxia
List the pathologic findings in Sickle Cell Disease
1. Sickle Cells
2. Microvascular occlusion -> thrombosis and infarction due to Sickle cells stuck in small vessels
3. Autosplenectomy = due to repeated bouts of infarction
4. Bone Marrow Hyperplasia = due to hemolytic anemia
5. Extramedullary hematopoiesis = when BM cannot keep up with need
6. Gallstones = due to increased Bilirubin from breakdown of Heme from Hb
Sickle Cell Disease
What disease is this?
Why is there pain in Sickle Cell Anemia?
Vaso-occlusive crises in the back or limbs due to microvasculature blockage by sickled cells
What would cause an Aplastic Crisis in Sickle Cell Anemia?
Parvovirus B19
What is the most common cause of death in Sickle Cell Anemia? Propose a possible mechanism

Mechanism: Autosplenectomy results in increased incidence of encapsulated organism infections
-Strep pneumo & Hib
-Salmonella -> Osteomyelitis
What is the treatment for Sickle Cell Anemia? Explain the reasoning

Increases the levels of HbF (gamma2 + delta2) while decreasing the levels of HbS
What does Sickle Cell Trait protect against?
Falciparum malaria
Describe the distribution of normal adult hemoglobin
1. HbA = 96%
2. HbA2 = 3% (alpha2/delta2)
3. HbF = 1% (alpha2/gamma2)
Define Thalassemias
Lack of or decreased synthesis of structurally normal hemoblogin chains
Describe the pathogenesis of Thalassemias
What ethnicities is Alpha-thalassemia most prevalent in?
Africa & SE ASIA
What ethnicities is Beta-thalassemia most prevalent in?
In Thalassemias, What 2 things does Free globin chain aggregates result in?
1. Destruction in the spleen

2. Ineffective erythropoiesis = premature destruction of maturing erythroblasts within the BM
What is Beta-Thalassemia and what is the cause?
1. Decreased synthesis of Beta chains

2. Point mutations causing:
-Splicing errors (most common)
-Promoter region (β+)
-Chain termination (β0)

**unlike Alpha-thalassemia, gene deletions are uncommon
Resulting anemia in Beta-Thalassemia
Hypochormic, microcytic anemia

**b/c there is less Hb = less heme = less iron in RBC
What Hb's are elevated in Beta-Thalassemia?
HbF (a2g2)

HbA2 (a2d2)
Pathological findings of Beta-thalassemia
1. Bone Marrow Hyperplasia
-cortical thinning = "crewcut" skull x-ray
=increased size of maxilla

2. Hepatosplenomegaly

3. Hemosiderosis
- hemolysis is taking place in BM and Spleen where Fe+ is recoverable
-Severe Thalassemias require blood transfusions

Target cells
What disease?

What are the cells called?
What disease causes "crewcut" skull on x-ray?
List the clinical features of Beta-Thalassemia Major
1. β0/β0 or β+/β+ = no functional Beta-globin
2. Severe anemia, ↑↑↑ HbF, ↑ HbA2
3. Transfusion dependent
4. Hemosiderosis
5. Treatment: BM transplant
6. Develops at 6 months of age when HbF levels decline

β0/β0 = do not produce β-chains at all

β+/β+ = reduced β-chain synthesis
What is the genotype for β-Thalassemia intermedia
β0/β, β+/β+

**severe anemia, but not enough to require regular blood transfusions
List the clinical features of β-Thalassemia minor
1. β0/β or β+/β = there is one normal Beta-globin gene
2. Asymptomatic
3. Mild anemia, ↑ HbF, ↑ HbA2
4. Protects against Falciparum malaria
What is the Etiology of Alpha-Thalassemias?
GENE DELETIONS of alpha chains

**there are 2 alpha genes on each of our Chr. 16 = 4 total
**can be various combos of deletions
What is the silent carrier state of Alpha-Thalassemia?
1 out of 4 alpha genes is deleted (-a/aa)
- completely asymptomatic
Describe the Alpha-Thalassemia Trait
2 deletions of the Alpha gene:
- (--/aa) or (-a/-a)
What is the concern with individuals with the Alpha-Thalassemia Trait?
If 2 individuals with the genotype (--/aa) mate, they can produce a child with Hydrops Fetalis = Genetic Counseling

*25% chance of offspring with Hydrops fetalis
Describe the HbH disease in Alpha-Thalassemia
3 deletions of Alpha chain (--/-a) causes increased HbH = tetramer of Beta chains (β4)
What is the result when there are 4 deletions of the Alpha gene in an individual?
Hydrops fetalis
Type of anemia in Alpha-Thalassemias
Hypochromic, microcytic anemia
What are the pathologic findings associated with Alpha-Thalassemia?
1. Hypochromic, microcytic anemia of variable severity
2. HbH disease
3. Bone Marrow Hyperplasia
4. Hepatosplenomegaly
What is Barts Hemoglobin (Gamma4) associated with?
Hydrops fetalis Alpha-Thalassemia (lacks all 4 alpha-globin chains)
Alpha-Thalassemia (HbH disease = 3 deletions)

Target cells in upper
Heinz bodies = HbH (β4)
What disease is this?

How do you know?
What ethnicity typically carries the cis genotype (--/αα)of the Alpha-Thalassemia trait?
Asians = if both partners have it there is a 25% chance of having child with intrauterine death
What ethnicity typically carries the trans genotype (a-/a-) of the Alpha Thalassemia trait?
Disease caused by an acquired deficiency of Glycosyl Phosphatidyl Inositol (GPI)-linked proteins due to mutations in Phosphatidylinositol Glycan A (PIGA)
Paroxysmal Nocturnal Hemoglobinuria
Describe the pathogenesis of Paroxysmal Nocturnal Hemoglobinuria
1. ↓ GPI anchored proteins (CD55, CD59, C8-binding protein, Decay Accelerating Factor)
2. ↑ complement sensitivity
3. Intravascular Hemolysis
How do you diagnose Paroxysmal Nocturnal Hemoglobinuria?
Look for the presence of cell surface proteins, if missing it means PNH
What are the clinical findings of Paroxysmal Nocturnal Hemoglobinuria?
1. Anemia
2. Hemosiderinuria --> leads to iron deficiency
3. Venous thrombi which may be fatal
What complications does Paroxysmal Nocturnal Hemoglobinuria cause an increased risk of? (3)
1. Aplastic anemia
2. Acute Leukemia
3. Venous thrombosis
What cell type has the acquired defect in Paroxysmal Nocturnal Hemoglobinuria?
Multipotent Myeloid Stem Cell
Why would Paroxysmal Nocturnal Hemoglobinuria occur at night?
Respiratory acidosis, which occurs during slow breathing that causes retention of CO2, causes activation of Complement
What Screening test and what Confirmatory tests are used in Paroxysmal Noctural Hemoglobinuria?
Screening = Sucrose Hemolysis
- sucrose enhances complement destruction of RBC's

Confirmatory = Acidified Serum Test (Ham test)
- acidified serum activates the Alternative complement pathway
What type of Anemias are Immunohemolytic anemias?
Extrinsic = environment is causing RBC destruction
Type of Antibody that causes Warm Autoimmune Hemolytic Anemia
IgG, active at 37' C
Describe the pathogenesis of Warm AIHA
1. IgG coated RBC
2. Fc receptor binds to Splenic Macrophages
3. Spherocytes
4. Destruction in the spleen = Extravascular
What are the Secondary causes of Warm AIMA?
1. Lymphoproliferative disorders = Lymphoma = B cell neoplasm making Ab's against RBCs
2. Autoimmune diseases = SLE
3. Drugs
What drugs can act as Haptens and cause Warm AIHA?
1. Quinidine
2. Penicillin
3. Cephalosporin
What drug can cause the production of an Autoantibody to RBC's causing Warm AIHA?

**causes production of an Ab that cross-reacts with RBC
What 2 disorders are characterized by Spherocytes and how do you differentiate?
1. Warm AIHA
2. Hereditary Spherocytosis

**Warm AIHA will be Direct Coomb's test + = tests for Ab's coated on RBC's
Type of Antibody that causes Cold Agglutinin Disease
Describe the Pathogenesis of Cold Agglutinin Disease
1. IgM coated RBC
2. RBC agglutination
3. Complement fixation
4. Intravascular and Extravascular Hemolysis
Why does Cold Agglutinin Disease cause agglutination and complement fixation?
IgM is a pentamer so it can latch onto more than one RBC = agglutination

Agglutination causes Complement activation
What are 2 acute causes of Cold Agglutinin Disease?
recovery from Mycoplasma pneumoniae

recovery from Infectious Mononucleosis
What are teh 2 chronic causes of Cold Agglutinin Disease?

Describe the Pathogenesis of Paroxysmal Cold Hemoglobinuria
IgG antibodies (cold hemolysins) bind to RBC at low temperature, fix complement, and cause hemolysis at temps above 30 C
What is the most important marker of Immune Hemolytic Anemias?
Direct Coombs test = direct antiglobulin test (DAT)

**Spherocytes are also caused by Hereditary Spherocytosis
Autoimmune hemolytic anemia that would cause this
Cold Agglutinin Disease
-IgM causes agglutination of RBC's at temperatures lower than body temp
What is this disease?
What are the clinical features of Warm AIHA?
1. Variably severe anemia -> Splenomegaly
2. Treatment is directed to the underlying cause
What are the clinical features of Cold Agglutinin Disease?
1. Variably severe anemia
2. Self limited
What is the clinical feature of Paroxysmal Cold Hemoglobinuria?
Intermittent massive hemolysis AFTER exposure to cold
Describe Macroangiopathic Hemolytic Anemia
RBC is hit against something which causes it to lyse
What are 2 possible causes of Macroangiopathic Hemolytic Anemia?
1. Aortic Stenosis

2. Prosthetic Heart Valves
Describe Microangiopathic Hemolytic Anemia
partial occlusion of small vessels is the cause of mechanical disruption of the RBC's
Give 6 examples of causes of Microangiopathic Hemolytic Anemia
1. DIC
2. Thrombotic Thrombocytopenic Purpura
3. Hemolytic Uremic Syndrome
4. Malignant Hypertension
5. SLE
6. Disseminated Cancer
What are the pathologic findings of Traumatic Hemolytic Anemia (Micro- or Macroantiopathic)

Micro- or Macroangiopathic Hemolytic Anemia = Trauma
What are these cells called?

What is the cause?
An 8-year-old AFRICAN AMERICAN boy presents complaining of SEVERE PAIN IN BOTH LEGS. The pain began after the boy attended a pool party and spent much of the day swimming and reports that he has suffered from severe bouts OF BACK AND CHEST PAIN in the past
Sickle Cell Disease
-Swimming and lack of oxygen prompted sickling of HbS
-Back and Extremity pain are due to VASO-OCCLUSIVE crises due to microvasculature blockage by sickled cells
What is usually the first clinical manifestation of Sickle Cell Disease?
Dactylitis = infarctions in the bones of the digits
= hand-foot syndrome (swelling)

Howell-Jolly bodies
This is a blood smear from a patient with Sickle Cell Disease. What does it indicate? What is the cell called?
B is correct
-Decreased Hemoglobin
-Increased HbA2
-usually asymptomatic