QUANTITATIVE RED CELL DISORDERS PART III Flashcards
- 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
HEREDITARY ELLIPTOCYTOSIS
considered a severe form of HE or HEREDITARY ELLIPTOCYTOSIS
Hereditary pyropoikilocytosis
- RBCs show thermal sensitivity.
- RBCs fragment at 41°C to 45°C
Hereditary pyropoikilocytosis
-or Southeast Asian Ovalocytosis
- a condition caused by mutation in the gene for band 3 that results in increased rigidity of the membrane
HEREDITARY OVALOCYTOSIS
- 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
OVERHYDRATED HEREDITARY STOMATOCYTOSIS
- or hereditary xerocytosis
- due to a defect in membrane cation permeability that causes RBCs to be dehydrated
DEHYDRATED HEREDITARY STOMATOCYTOSIS
-RBC membrane is excessively permeable to potassium
- potassium leaks out of the cell
DEHYDRATED HEREDITARY STOMATOCYTOSIS
Other Hereditary Membrane Defects
I. Familial Pseudohyperkalemia
II. Cryohydrocytosis
III. Rh Deficiency Syndrome
is a term used to describe a group of rare inherited disorders characterized by neurologic impairment and acanthocytes on the PBS
Neuroacanthocytosis
Other Hereditary Membrane Defects with Acanthocytosis
Neuroacanthocytosis
Abetalipoproteinmeia
McLeod
Chorea acanthocytosis
Other Hereditary Membrane Defects with Acanthocytosis
characterized by chorea, hyperkinesia, cognitive impairments, and neuropsychiatric symptoms
Chorea acanthocytosis
an X-linked disorder caused by mutations in the KX gene
McLeod Syndrome
characterized by fat malabsorption, progressive ataxia, neuropathy, retinitis pigmentosa, and acanthocytosis
Abetalipoproteinmeia
caused by an acquired clonal hematopoietic stem cell mutation that results in circulating blood cells that lack CD55 and CD59
PAROXYSMAL NOCTURNAL HEMOGLOBINURIA
-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
PAROXYSMAL NOCTURNAL HEMOGLOBINURIA
PAROXYSMAL NOCTURNAL HEMOGLOBINURIA
Laboratory diagnosis:
I. Sugar water test
II. Sucrose hemolysis test
III. Acidified serum test/ Ham test
complement is activated by the alternative pathway, binds to red cells, and lyse the abnormal PNH cells
Acidified serum test/ Ham test
Principle: same as sugar water test
Sucrose hemolysis test
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)
Sugar water test
is the most common RBC enzyme defect
GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY
confers protection against life-threatening P. falciparum and P. vivax
GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY
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
G6PD
G6PD Laboratory diagnosis:
Ascorbate cyanide screening test - detects deficiencies in the pentose phosphate pathway
-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
YRUVATE KINASE DEFICIENCY
- 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
IMMUNE HEMOLYTIC ANEMIAS
Clearance of C3b-sensitized RBC by macrophages mainly in liver
Extravascular hemolysis IgM Mediated
- Formation of spherocytes by partial phagocytosis of——-sensitized RBCs
- Clearance of——- and C3b-sensitized RBCs by macrophages in spleen and liver
Extravascular hemolysis IgG mediated
- Full—— activation of classical complement pathway
- Direct RBC lysis
Intravascular hemolysis IgM Mediated
Full IgG activation of classical complement pathway
- Direct RBC lysis
Intravascular hemolysis IgG Mediated
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
Warm autoimmune hemolytic anemia
- 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
Cold agglutinin disease
- 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
Paroxysmal cold hemoglobinuria
- 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.
Drug-induced immune hemolytic anemia
- 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
Drug-induced immune hemolytic anemia
- hemolysis is predominantly extravascular by hepatic macrophages
- symptoms include acrocyanosis (a bluish discoloration of the extremities
Cold agglutinin disease
