QUANTITATIVE RED CELL DISORDERS PART III

Question 1

• caused by defects in proteins that disrupt the horizontal or lateral interactions in the protein cytoskeleton
• characteristic finding: elliptical or cigar-shaped RBCs on the peripheral blood film

Answer 1

HEREDITARY ELLIPTOCYTOSIS

Question 2

considered a severe form of HE or HEREDITARY ELLIPTOCYTOSIS

Answer 2

Hereditary pyropoikilocytosis

Question 3

• RBCs show thermal sensitivity.
• RBCs fragment at 41°C to 45°C

Answer 3

Hereditary pyropoikilocytosis

Question 4

-or Southeast Asian Ovalocytosis
- a condition caused by mutation in the gene for band 3 that results in increased rigidity of the membrane

Answer 4

HEREDITARY OVALOCYTOSIS

Question 5

• due to a defect in membrane cation permeability that causes RBCs to be over hydrated
• the RBC membrane is excessively permeable to sodium and potassium at 37°C

Answer 5

OVERHYDRATED HEREDITARY STOMATOCYTOSIS

Question 6

• or hereditary xerocytosis
• due to a defect in membrane cation permeability that causes RBCs to be dehydrated

Answer 6

DEHYDRATED HEREDITARY STOMATOCYTOSIS

Question 7

-RBC membrane is excessively permeable to potassium
- potassium leaks out of the cell

Answer 7

DEHYDRATED HEREDITARY STOMATOCYTOSIS

Question 8

Other Hereditary Membrane Defects

Answer 8

I. Familial Pseudohyperkalemia
II. Cryohydrocytosis
III. Rh Deficiency Syndrome

Question 9

is a term used to describe a group of rare inherited disorders characterized by neurologic impairment and acanthocytes on the PBS

Answer 9

Neuroacanthocytosis

Question 10

Other Hereditary Membrane Defects with Acanthocytosis

Answer 10

Neuroacanthocytosis
Abetalipoproteinmeia
McLeod
Chorea acanthocytosis

Question 11

Other Hereditary Membrane Defects with Acanthocytosis

characterized by chorea, hyperkinesia, cognitive impairments, and neuropsychiatric symptoms

Answer 11

Chorea acanthocytosis

Question 12

an X-linked disorder caused by mutations in the KX gene

Answer 12

McLeod Syndrome

Question 13

characterized by fat malabsorption, progressive ataxia, neuropathy, retinitis pigmentosa, and acanthocytosis

Answer 13

Abetalipoproteinmeia

Question 14

caused by an acquired clonal hematopoietic stem cell mutation that results in circulating blood cells that lack CD55 and CD59

Answer 14

PAROXYSMAL NOCTURNAL HEMOGLOBINURIA

Question 15

-the absence of CD55 and CD59 on the surface of the RBCs renders them susceptible to spontaneous lysis by complement
- mutation in the PIGA gene

Answer 15

PAROXYSMAL NOCTURNAL HEMOGLOBINURIA

Question 16

PAROXYSMAL NOCTURNAL HEMOGLOBINURIA
Laboratory diagnosis:

Answer 16

I. Sugar water test
II. Sucrose hemolysis test
III. Acidified serum test/ Ham test

Question 17

complement is activated by the alternative pathway, binds to red cells, and lyse the abnormal PNH cells

Answer 17

Acidified serum test/ Ham test

Question 18

Principle: same as sugar water test

Answer 18

Sucrose hemolysis test

Question 19

Principle: sugar water solution is added to provide a medium of low ionic strength that promotes the binding of
complement to the red cells

Result:
<5% hemolysis - negative
6%-10% hemolysis - borderline
>10% - positive ( to be confirmed with sucrose hemolysis test/ham test)

Answer 19

Sugar water test

Question 20

is the most common RBC enzyme defect

Answer 20

GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY

Question 21

confers protection against life-threatening P. falciparum and P. vivax

Answer 21

GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY

Question 22

RBCs are particularly vulnerable to oxidative damage and subsequent hemolysis during oxidant stress
———- is one of the important intracellular enzymes needed to protect hemoglobin and other cellular proteins and lipids from oxidative denaturation;———- catalyzes the first step in a series of reactions that detoxify hydrogen peroxide formed from oxygen radicals

Answer 22

G6PD

Question 23

G6PD Laboratory diagnosis:

Answer 23

Ascorbate cyanide screening test - detects deficiencies in the pentose phosphate pathway

Question 24

-the most common form of hereditary nonspherocytic hemolytic anemia

• is due to mutation in the PKLR gene
• metabolic consequence: depletion of ATP and an increase in 2,3 - BPG

Answer 24

YRUVATE KINASE DEFICIENCY

Question 25

- are conditions in which RBC survival is shortened due to an antibody-mediated mechanism. The antibody may be an autoantibody, an alloantibody, or an antibody directed against a drug taken by the patient

Answer 25

IMMUNE HEMOLYTIC ANEMIAS

Question 26

Clearance of C3b-sensitized RBC by macrophages mainly in liver

Answer 26

Extravascular hemolysis IgM Mediated

Question 27

- Formation of spherocytes by partial phagocytosis of——-sensitized RBCs - Clearance of——- and C3b-sensitized RBCs by macrophages in spleen and liver

Answer 27

Extravascular hemolysis IgG mediated

Question 28

- Full—— activation of classical complement pathway - Direct RBC lysis

Answer 28

Intravascular hemolysis IgM Mediated

Question 29

Full IgG activation of classical complement pathway - Direct RBC lysis

Answer 29

Intravascular hemolysis IgG Mediated

Question 30

is the most commonly encountered autoimmune hemolytic anemia - the autoantibodies react optimally at 37°C - onset is usually insidious, with symptoms of anemia - hemolysis is predominantly extravascular - polychromasia and spherocytes are the typical findings on the peripheral blood film

Answer 30

Warm autoimmune hemolytic anemia

Question 31

- cold agglutinins are of IgM class that react optimally at 4°C and are commonly found in healthy individuals - pathologic ———can react at body temperature

Answer 31

Cold agglutinin disease

Question 32

- is due to a biphasic IgG autoantibody with an anti-P specificity - at cold temperatures, the antibody binds to the P antigen on RBCs and partially activates complement - full complement activation and hemolysis occur only upon warming to 37°C

Answer 32

Paroxysmal cold hemoglobinuria

Question 33

- is suspected when there is a sudden decrease in hemoglobin after administration of a drug, clinical and biochemical evidence of extravascular or intravascular hemolysis, and a positive DAT results.

Answer 33

Drug-induced immune hemolytic anemia

Question 34

- unifying theory: proposes that a drug interacts with the RBC membrane and generates multiple immunogenic epitopes that can elicit an immune response to the drug alone, to the drug-RBC membrane protein complex, or to an RBC membrane protein alone

Answer 34

Drug-induced immune hemolytic anemia

Question 35

- hemolysis is predominantly extravascular by hepatic macrophages - symptoms include acrocyanosis (a bluish discoloration of the extremities

Answer 35

Cold agglutinin disease