RBC DISORDERS 2 Flashcards

1
Q

Quantitative vs Qualitative

  1. Anemia
    - blood loss
    - decreased production
    - increased destruction
  2. Polycythemia
A

Quantitative

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2
Q

Quan vs Quali

  1. abnormal in morphology
    - abnormal in function
    - intracorpuscular/Inherent to red cells
A

Quali

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3
Q

Reduction, from baseline value of:
– total Red Blood Cells (RBCs)
– circulating Hemoglobin (Hb)
– amount of Hematocrit (Hct)

A

Anemia

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4
Q
Parameters of Anemia
Adult Male
RBC: 
Hematocrit: 
Hemoglobin:  

Adult Female
RBC:
Hematocrit:
Hemoglobin:

A

Adult Male
RBC: 4.6 – 6.0 x 1012/L
Hematocrit: 40 – 50 % (0.40 – 0.50 L/L)
Hemoglobin: 14.0 – 18.0 g/dL (140 – 180 g/L)

Adult Female
RBC: 4.0 – 5.4 x 1012/L
Hematocrit: 35 – 49 % (0.35 – 0.49 L/L)
Hemoglobin: 12.0 – 15.0 g/dL (120 – 150 g/L)

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5
Q

Result of the compensatory mechanism to Anemia

A

Erythropoiesis (increased reticulocytes in the peripheral blood

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6
Q

• also known as Minkowski–Chauffard syndrome
• Intrinsic defect in the red blood cell membrane skeleton
• Inherited disorder:
– 75% - an autosomal dominant inheritance pattern
– Compound heterozygosity (inheritance of 2 different defect)
• Highest prevalence in Northern Europe – 1 in 5,000
- autosomanl dominant disorder
- characterized by 1. spherocytes, 2. splenomegaly, 3. familial occurence

A

HEREDITARY SPHEROCYTOSIS

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7
Q

Clinical manifestations:Hereditary Spherocytosis

A
  • chronic anemia,
  • splenomegaly,
  • gallstones (bilirubin stones) ,
  • aplastic crisis.
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8
Q

Defect in Hereditary Spherocytosis

A

Deficiency of Beta Spectrin or Ankyrin -> Loss of membrane -> becomes more spherical -> Destruction in Spleen

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9
Q

Laboratory of Hereditary Spherocytosis

A
  1. Those of chronic extravascular hemolysis
  2. Increased pigment catabolism
  3. Erythroid hyperplasia
  4. Reticulocytosis
  5. Direct antiglobulin test (DAT) – negative
  6. MCV normal; MCHC often increased
  7. OFT increased
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10
Q
  • Red cells arte suspended in a series of tubes containing hypotonic solutions of NaCl varying from 0.9 to 0.0%, incubated at room temperature for 30 minutes, and centrifuged.
  • cells with decreased surface/volume ration, have limited capacity to expand in hypotonic solutions, hence undergo lysis.
A

Osmotic Fragility Tests

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11
Q
  • Sterile, defibrinated blood is incubated at 370C for 48 hours.
  • Cells undergo series of changes —- become more spherocytic
A

Autohemolysis Tests

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12
Q

HEREDITARY SPHEROCYTOSIS
Clinical Features:

  • Triggered by Acute parvovirus infection. Around 1-2 weeks
  • Produced by intercurrent events (ie infectious mononucleosis) -> increased spleenic destruction.
A
  • Aplastic Crises

- Hemolytic Crises

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13
Q

Tx for HEREDITARY SPHEROCYTOSIS

A
  • Supportive

- Splenectomy

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14
Q
  • is involved in the Hexose Monophosphate shunt/Pentose Phospate Pathway -> Reduction of oxidized form of glutathione/detoxifies accumulated peroxide.
  • Recessive x-linked trait: Males > Females
  • Variants that cause most of the clinically significant Hemolytic anemia:
    1. G6PD-
  • 10% of Americal Blacks
    2. G6PD Mediterranean – prevalent in the Middle East
    • Protective against Plasmodium falciparum
A

Glucose-6-Phosphate Dehydrogenase

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15
Q

Triggers of hemolysis in GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY

A
  1. Infections
    - Viral hepatitis, Pneumonias, Typhoid fever
  2. Drugs
    - Anti-malarial drugs, Sulfonamides, Nitrofurantoin
  3. Food – Fava beans
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16
Q

GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY
Clinical Features:
Acute Hemolysis
Recovery phase:

A

Usually starts 2 to 3 days following exposure

  • Characteristics
    1. Anemia
    2. Hemoglubinuria
    3. Hemoglobinemia
  • No features related to chronic hemolysis (splenomegaly and cholelithiasis.

Recovery phase:
- Reticulocytosis

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17
Q

Detects deficiencies in the pentose phosphate pathway:

  • Glucose-6-Phosphate
  • Dehydrogenase deficiency
  • Glutathione reductase
  • Glutathione peroxidase
A

Ascorbate Cyanide Screening Test

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18
Q

Morphology of GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY

  • macrophages eat the red blood cells
  • due to high level of oxidants -> cross-linking of reactive sulfhydryl groups of hemoglobin -> denatured hemoglobin
A
  • bite cells

- Heinz bodies

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19
Q

• An inherited disease of the red blood cells that is common among blacks
• Affect the proteins inside the red blood cells - HEMOGLOBIN.
• Deoxygenated red blood undergo transformation from normal biconcave disk to sickle - shaped structure.
- sickling phenomenon is due to polymerization of sickle hemoglobin Hb S
-

A

SICKLE CELL DISEASE

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20
Q
  • HB SS (α2βς2) - due to point mutation

- Valine is substituted for glutamic acid at the 6th position of β - globin chain.

A

Homozygous form

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21
Q

• Red blood cells sickle when O2 saturation is < 40%
Example: Unpressurized aircraft, Deep sea diving
• Does not affect life span of patient.
• Normal blood counts and morphology
• Does not require treatment

A

Heterozygous form - Hb AS

22
Q

Major Pathologic Manifestations: Sicle Cell Disease

A
  1. Chronic hemolysis
  2. Microvascular occlusion
  3. Tissue damage
23
Q

SICKLE CELL DISEASE Morphology:

  1. Peripheral blood picture
    - Anemia -
    - Increased polychromasia -
    - Normoblast
    - Target cells
    - Howell - Jolly and Pappenheimer bodies
    - Sickle cells
A
  1. Peripheral blood picture
    - Anemia - usually normocytic normochromic
    - Increased polychromasia - reticulocytosis
    - Normoblast may be seen
    - Numerous Target cells
    - Howell - Jolly and Pappenheimer bodies
    - Numerous Sickle cells
24
Q

SICKLE CELL DISEASE Morphology:

Bone marrow

A

Bone marrow

  • Normoblastic hyperplasia
  • Increased Iron storage
25
Diagnose: - Cellulose acetate electrophoresis at pH 8.6 - 35 - 45 % Hb S Normal Hb F - 50 - 65 % Hb A Normal to slightly inc. Hb A2
Hemoglobin Electrophoresis
26
• Adding Sodium Metabisulfite to blood enhances deoxygenation and sickling of the red blood cell. • Drawback: 1. Does not distinguish Hb AS from Hb SS and other Hb S syndromes. 2. Positive test may occur with other rare abnormal hemoglobin (Hb C Harlem and Hb I). 3. False negative test may occur if Hb S is less than 10% or there is inadequate deoxygenation.
Sickling Test – Metabisulfite
27
* Adding Sodium hydrosulfite results to lysis of RBC and reduction of Hb S. * Polymers of Hb S obstruct light rays and produce opacity. * Useful for screening
Solubility Test – Dithionate
28
* Increasing proportion of red blood cells lyse upon exposure to increasing hypo-osmotic saline solution. * OFT usually decreased * Not specific
Osmotic Fragility Test
29
SICKLE CELL DISEASE | Treatment:
1. Symtomatic - Pain Management - Narcotics ex. Morphine and Hydromorphone - Reduce number of “crises” HYDROXYUREA (Charade) Exchange Transfusion 2. Bone marrow transplant
30
* the medical term for a deficiency in the number of red blood cells (anemia) * Heterogenous group of heritable anemias that have in common quantitatively defective synthesis of either α or β chains of the normal hemoglobin A tetramer (α2β2) * Originally observed in Italian and Greek coast. * Also seen in the Mediterrenean basin, Middle East, Parts of Pakistan, India, Southeast Asia, Southern Part of USSR, China and Northern Regions of African continent. * Most frequent in malaria epidemic areas.
THALASSEMIA
31
Alpha VS Beta Thalassemia - deletions of alpha-globin gene - symptoms can begin in fetal life - complicated inheritance- 4 alpha genes
Alpha
32
Alpha VS Beta Thallasemia - nonsense, splice and frameshift mutations in beta globin gene - symptoms begin in infncy/childhood - simple AR inheritance; genotype-phenotype correlation
Beta
33
β-THALASSEMIA Molecular Pathogenesis: Extremely heterozygous 1. Most commonly by ____ on chromosome 11 2. Less commonly ____ of part of the gene
- point mutation | - deletion
34
β-THALASSEMIA Molecular Pathogenesis: Categories 1. βo mutations associated with ___ β-globin synthesis 2. β+ mutations ___ but detectable βo sythesis
- absent | - reduced
35
Mechanism of Anemia (β-THALASSEMIA):
1. Deficiet Hb A synthesis - “Underhemoglobinization” microcytic hypochromic red cells with abnormal oxygen transport capacity - Diminished survival of red cells and their precursors 2. Ineffective erythropoiesis 3. Extravascular Hemolysis
36
Manifestation of 1.Heterozygous β- Thalassemia/β- Thalassemia Minor/ Cooley’s Trait (β0/β or β+/β)
- Moderate reduction of Hb A (α2 β2) | - Increased Hb A2 (α2δ2)
37
Manifestation of Homozygous β -Thalassemia / β -Thalassemia Major/ Cooley’s Anemia (β0 /β0 or β+/ β+)
Normal or moderately increased Hb A2 (α2δ2) | * Increased Hb F (α2γ2)
38
β – Thalassemia Morhology: Peripheral Blood - mild anemia with some hypochromia and microcytosis - poikilocytosis - basophilic stippling - target cells
Heterozygous
39
β – Thalassemia Morhology: Peripheral Blood - hypochromic and microcytic anemia - marked anisocytosis and poikilocytosis - target cells, ovalocytes, siderocytes, nucleated RBCs - extreme normoblastosis - cabot rings, howell-jolly bodies
Homozygous
40
β – Thalassemia Morhology: Bone Marrow - Normoblastic hyperplasia and increased Iron storage - Marked normoblastic hyperplasia, Increased Iron storage, Increased sideroblast, Normoblast with inclusions
- Heterozygous | - Homozygous
41
β – Thalassemia Morhology: Heterozygous vs Homozygous: Osmotic Fragility Test Blood Indices Increased Indirect Bilirubin
Heterozygous - Decreased OFT - Increased RBC - Decreased HCT and Hb - Low MCH and MCV; N to Low MCHC Homozygous - Increased OFT - Severe derangement Increased Indirect Bilirubin: ALL
42
β – Thalassemia Treatment: | Symtomatic
1. Iron chelation | 2. Transfusion therapy
43
``` - Reflects the failure of one or more of the four (4) α - gene loci on chromosome 16 to function. Histopathogenesis: - 80 % of cases reflect gene deletion - less commonly by point mutation ``` - Limited to the tropical and subtropical regions of the world. - Carriers have been reported to resist infection by Plasmodium falciparum.
Alpha – Thalassemia
44
Alpha – Thalassemia Syndrome: - Deletion of one (1) α gene or inactivation by point mutation. - Hematologic parameters are normal. - Infants have 1 to 2 % of total Hb is Hb Bart’s.
Silent Carrier State /α+ - Thalassemia or α- - Thalassemia 2 /(αα/α-)
45
Alpha – Thalassemia Syndrome: - Deletion of two (2) gene 3 Molecular mechanisms: a. Deletions - 17 different types b. Truncation of chromosome 16 c. Removal of the key regulatory region HS 40 - Mild hemolytic anemia - Infants have Hb Bart’s of no more than 5 %
α - Thalassemia Trait / α –Thalassemia Minor /α 0- Thalassemia or α+ -Thalassemia 1/(αα/-- or α-/α-)
46
Alpha – Thalassemia Syndrome: - 3 genes deleted - Moderate hemolytic anemia with hypochromia and microcytosis. - First year of life with up to 25 % Bart’s Hb - Adult Hb A predom
Hemoglobin H Disease (α-/-- or αα/-- cs)
47
Alpha – Thalassemia Syndrome: - Complete deletion of 4 genes - Death in - utero or Hydrops fetalis
Bart’s Hemoglobin
48
Diagnosis - Alpha - Thalassemia | All forms of Thalassemia show:
1. Hypochromic microcytic anemia 2. Ineffective erytropoiesis 3. Hemolysis
49
Diagnosis - Alpha - Thalassemia: | Hydrops with Bart’s Hb
- Marked anisocytosis and poikilocytosis - Marked microcytosis and erythroblastosis - Absent ABO and Rh incompatibility - Alkaline Electrophoresis: Large quantities of Hb Bart’s (γ4) Some Hb H (β4)
50
Diagnosis - Alpha - Thalassemia: Hemoglobin H Disease - Blood - Electrophoresis
``` - Blood: Decreased MCV and MCH > Hypochromia, target cells and anisopoikilocytosis > Reticulocytes usually 4 to 5 % > Hb H precipitates (BCB) > Heinz bodies - Electrophoresis: > Hb H (β4) accounts for 4 to 30 % > Traces of Hb Bart’s (γ4) ```