ANEMIA CAUSED BY INCREASE DESTRUCTION OF RBCS Flashcards
- Commonly inherited as an autosomal dominant trait
- Defects in proteins that disrupt the vertical interactions between transmembrane proteins and the underlying protein cytoskeleton.
Hereditary Spherocytosis
Hereditary Spherocytosis:
Loss of ______ attached to RBC cytoskeleton
_____surface area-to-volume ratio
lipid membrane
Decrease
Hereditary Spherocytosis:
3 Clinical Manifestations:
- Anemia
- Jaundice
- Splenomegaly
Hereditary Spherocytosis distinguished from immune-related hemolytic anemia thru _____
DAT
Hereditary Spherocytosis:
Lab Findings:
- Uniform ____ on PBS
- MCHC _____
- ___ Osmotic Fragility Test (OFT)
Spherocytes
High (>36%)
Increase result in Osmotic Fragility Test (OFT)
Hereditary Spherocytosis:
Hemolysis at ___
> 0.45% NaCl
Traditional test method for H.S
Osmotic Fragility Test (OFT)
Hereditary Spherocytosis:
Specimen:
Heparinized blood
Hereditary Spherocytosis:
Reagent:
Different concentrations of NaCl Solutions (0.85% to 0%)
Hereditary Spherocytosis:
OFT Normal Results:
Initial hemolysis at ____
Complete hemolysis at ____
0.45% NaCl
0.35% NaCl
Hereditary Spherocytosis:
Incubating the blood at 37C for ____ before performing the test (Incubated OFT) allows HS cells to become more ___ and is often needed to detect mild cases
25 hours
spherical
Has been proposed as a more sensitive alternative for confirmation of H.S.
Eosin-5’ – maleimide binding test (EMA)
Eosin-5’ – maleimide binding test (EMA)
PRINCIPLE:
Flow Cytometry
Eosin-5’ – maleimide binding test (EMA):
EMA results with H.S
Lower
Gene mutation that disrupts horizontal RBC cytoskeleton
Hereditary Elliptocytosis
Elliptocytosis can also be seen in patients with the Leach phenotype who lack ______
Gerbich antigens
___ is the null/absent phenotype under the Gerbich Blood group system
Leach phenotype
Majority of patients with HE are ________, and only about __% have moderate to severe anemia
asymptomatic
10
RBCs show some degree of a low thermal stability (fragments at 45C)
Hereditary Pyropoikilocytosis
Hereditary Elliptocytosis:
Observed in individuals who lack _______ on their RBC membrane
Glycophorin C
Condition caused by a mutation in the gene for band 3
= increased rigidity of the membrane and resistance to invasion by malaria.
Hereditary Ovalocytosis / Southeast Asian Ovalocytosis
Hereditary Ovalocytosis / Southeast Asian Ovalocytosis:
Condition caused by a mutation in the gene for ____ that results in increased rigidity of the membrane and resistance to invasion by ____
band 3
malaria
Hereditary Stomatocytosis:
Major categories:
Defect in membrane cation permeability (Na, K), resulting in a net increase in the intracellular cation concentration. More water enters the
cell causing swelling.
Overhydrated HS (Hereditary hydrocytosis)
Hereditary Stomatocytosis:
Major categories:
- Most common form of stomatocytosis
- Defect in membrane cation permeability, resulting in a reduced intracellular cation concentration.
- Water is lost from the cell.
Dehydrated HS (Hereditary xerocytosis)
Group of rare inherited disorders characterized by neurologic impairment and acanthocytes on the peripheral blood film
Neuroacanthocytosis
Neuroacanthocytosis
3 disorders included are:
Abetalipoproteinemia
Mcleod syndrome
Chorea acanthocytosis
LDL deficiency
Abetalipoproteinemia
weak expression of Kell ag
Mcleod syndrome
Rare chronic intravascular hemolytic anemia caused by an acquired clonal HSC mutation
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Results to blood cells which lack ____
glycosylphosphatidylinositol (GPI)-anchored
proteins
Paroxysmal Nocturnal Hemoglobinuria (PNH)
DAF- decay accelerating factor
CD55
Paroxysmal Nocturnal Hemoglobinuria (PNH)
MIRL- membrane inhibitor of reactive lysis
CD59
- Most common RBC enzyme defect (5% of the global population)
- Inability to generate sufficient NADPH to reduce glutathione
G-6PD Deficiency
G-6PD Deficiency:
Inability to generate sufficient _____ to reduce ____
NADPH
glutathione
____ is needed to detoxify peroxides and protect red cells from oxidative stress
Glutathione
G-6PD Deficiency:
Clinical findings:
Acute hemolytic anemia
Neonatal jaundice
Favism (severe hemolytic episode upon ingestion of Fava beans)
G-6PD Deficiency:
Lab findings:
H______
_____ cells on PBS
Heinz bodies
Bite cells
G-6PD Deficiency:
Screening tests:
Ascorbate Cyanide Test
Fluorescent Spot Test
Gold standard in detection of G-6PD Deficiency
Quantitative spectrophotometric assay
G-6PD Deficiency
Quantitative spectrophotometric assay
Specimen:
Heparinized or EDTA-whole blood
causes the formation of bite cells
Splenic pitting
Under what pathway is G6PD deficiency
Hexose monophosphate pathway/Pentose Phosphate Pathway (PPP)
Autosomal recessive disorder; most common form of hereditary nonspherocytic hemolytic anemia
Pyruvate Kinase Deficiency
Pyruvate Kinase Deficiency:
Causes _____ of cellular ATP, which affects the ability of the cell to maintain its shape
depletion
Pyruvate Kinase Deficiency:
Clinical findings:
_____ anemia
______bilirubinemia
Splenomegaly
Neonatal anemia
Hyperbilirubinemia
Pyruvate Kinase Deficiency:
Lab work-up:
______ PK assay on RBC ________
Quantitative
Hemolysate
Pyruvate Kinase Deficiency:
Quantitative PK assay on RBC hemolysate:
The rate of NAD formation is proportional to PK activity and is measured as a decrease in absorbance at ____ nm
340
Under what pathway is Pyruvate Kinase deficiency
Embden Meyerhof pathway
