Hemolytic Anemias 1

Question 1

Hereditary Spherocytosis (HS)

Answer 1

Caused by mutations that affect the vertical membrane interactions
Combined ankyrin and spectrin deficiency, or isolated band 3, spectrin, or protein (band) 4.2 deficiencies
Spherocytes are more sensitive to hemolysis, have a shortened life span

Question 2

HS Labs

Answer 2

Decreased Hgb, Hct, MCV
Increased Retic (>8%)
MCHC >36 g/dL 
Increased osmotic fragility test
Negative DAT

Question 3

HS Microscopics

Answer 3

Spherocytes, polychromasia

Question 4

Hereditary Elliptocytosis

Answer 4

Caused by mutations in the RBC cytoskeletal proteins
Defective spectrin chains, mutation in band 4.1, abnormalities in glycophorin C and increased affinity of band 3 for ankyrin (increased cell rigidity)

Question 5

Common HE

Answer 5

Poikilocytosis increases with the amount of hemolysis that occurs
Elliptocytosis can range from 25 to 100%
Alytic to severely hemolytic

Question 6

Spherocytic HE (Hemolytic Ovalocytosis)

Answer 6

Both spherocytes and elliptocytes can be seen

Hemolytic

Question 7

Stomatocytic HE

Answer 7

Melanisian Ovalocytosis, SE Asian Ovalocytosis
Mild or absent hemolysis
Elliptocytes and stomatocytes also present

Question 8

HE Labs

Answer 8

Non hemolytic: normal
Hemolytic: Decreased Hgb, Hct, RDW,
Increased RDW, Retic (up to 20%)

Question 9

HE Microscopics

Answer 9

> 25% elliptocytes, poikilocytosis, spherocytes, schistocytes

Question 10

Hereditary Pyropoikilocytosis

Answer 10

Very severe form of HE
Caused by two heterozygous autosomal recessive mutations
Alpha spectrin deficiency, mutation impairing the formation of spectrin tetramers
RBCs fragment when heated to 45-46C (normal at 48-50C)
Spectrin degrades at 48C

Question 11

HP Labs

Answer 11

Decreased Hgb, Hct

Increased RDW, Retic

Question 12

HP Microscopics

Answer 12

Extreme poikilocytosis, RBC membrane budding, micro-spherocytes, schistocytes, RBC fragmentation

Question 13

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Answer 13

Acquired HSC defect, not inherited, doesn't affect all RBCs
Somatic mutation in PIGA class A gene
Increased sensitivity of RBCs to complement lysis is associated with the classic symptoms of intermittent intravascular hemolysis at night

Question 14

PNH Labs

Answer 14

Decreased Hgb (8-10), Hct
Increased Retic (5-10%) 
Old tests: Ham's test, sucrose lysis test
Current tests: CD55, CD59 quantification by flow cytometry (decreased), FLAER test

Question 15

PNH Microscopics

Answer 15

Thrombocytopenia, leukopenia, normochromic, normocytic

Question 16

Glucose-6-Phosephate Dehydrogenase Deficiency

Answer 16

X linked recessive mutation in the G6PD enzyme
Excess oxidizers will oxidize hemoglobin, causing it to precipitate as Heinze bodies
Bodies are removed in the spleen, results in bite cells

Question 17

G6PDD Labs

Answer 17

Non-Hemolytic: normal
Recent Hemolysis: decreased Hgb, Hct, Haptoglobin
Increased WBC, Retic

Question 18

G6PDD Microscopics

Answer 18

Polychromasia, bite cells, blister cells, occasional spherocyte, increased Heinz bodies