Anemia 3 Flashcards
ANEMIAS OF ABNORMAL GLOBIN DEVELOPMENT
THE THALASSEMIAS
are a diverse group of genetic disorders characterized by a primary, QUANTITATIVE reduction in globin chain synthesis for hemoglobin.
THE THALASSEMIAS
The thalassemias are usually classified according to the particular globin chain whose synthesis is suppressed. The types are:
a-thalassemia b -thalassemia g -thalassemia d-thalassemia db-thalassemia gdb-thalassemia
The genetics of thalassemia is centralized to the structures of CHROMOSOME _ and _
11
16
differentiates thalassemia from Hereditary Persistence of Fetal Hemoglobin (HPFH)
Acid elution testfor Hb F:
HEMATOLOGY
Microcytic hypochromic anemia
WBC and platelets are not involved
SPECIAL HEMATOLOGY TESTS
Bone marrow: Hyperplastic red cell precursors
Hemoglobin electrophoresis on cellulose acetate at alkaline pH
Citrate agar electrophoresis (acid pH)
THALASSEMIAS
Most important test to differentiate Iron deficiency from thalassemia
Ferritin:
a-thalassemia
a DOUBLE gene deletion (- - )
a SINGLE gene deletion (- a)
a thalassemia-1 or 1° thalassemia
a thalassemia-2
Caused by a deletion of all 4 a globin chains (- -/- -)
BART’S HYDROPS FETALIS
Deletion of 3 or 4 a globin genes (- -/- a)
Non deletional forms exists (aaT/aaT and aaT/- -)
HbH DISEASE
CS consists of 2 normal b chains, one normal a chain and one abnormal a chain that has 172 amino acids as opposed to normal 141.
Occurs frequently in Orientals (SE Asia)
Hb H – CONSTANT SPRING DISEASE (Hb CS)
Heterozygous a° (- -/aa)
Homozygous a+ (-a/-a)
a THALASSEMIA MINOR
Heterozygous a+ thalassemia
Associated with one a gene deletion (-a/aa)
THE SILENT CARRIER
b THALASSEMIA MAJOR
Four genotypes
b°/b°
b+/b+ (Mediterranean form)
b°/b+
is composed of normal a chains and two abnormal a chains formed by fusion of N-terminal end of the d chain and the C-terminal of the b chain
Hb Lepore
Hb Lepore consists of 3 types:
Hb Lepore-Baltimore
Hb Lepore-Boston (most common)
Hb Lepore-Hollandia
b THALASSEMIA INTERMEDIA
Less impairment of b chain synthesis than the homozygous b+ thalassemia
Homozygous b+ thalassemia (b+/b+) Mild Black Form
b THALASSEMIA INTERMEDIA
Caused by deletion on the d and b structural genes on chromosome 11
More efficient synthesis of g chains; the g chain bind with a chains to form Hb F, which constitutes 100% of hemoglobins in patients)
Homozygous db thalassemia (db°/db°)
Describes a heterogenous group of inherited disorders characterized by increased levels of Hb F in a dults in the absence of usual clinical and hematologic features of thalassemia
Characterized either by deletion or inactivation of the b and d structural gene complexes
HEREDITARY PERSISTENCE OF FETAL HEMOGLOBIN
Test for Hb H Inclusions
Brilliant Cresyl Blue (BCB)
Test for Hb F
Acid Elution Slide
Cells containing HbF will be stained ___ whereas normal adult cells appear as “ghost cells” (only the outer membranes are visible.
BRIGHT PINK TO RED
ANEMIA OF INCREASED ERYTHROCYTE DESTRUCTION
THE HEMOLYTIC ANEMIAS
Classification of Hemolytic Anemias
INTRINSIC HEMOLYTIC ANEMIAS
--Hereditary Membrane Defects Enzyme Defects Hemoglobinopathies Acquired
Hereditary Spherocytosis
Hereditary Elliptocytosis
Hereditary Pyropoikilocytosis
G6PD Deficiency
Pyruvate kinase Deficiency
Glutathione reductase deficiency
Hemoglobin SS, CC, SC, and S-b thalassemia
Paroxysmal Nocturnal Hemoblobinuria (PNH)
EXTRINSIC HEMOLYTIC ANEMIAS
Hereditary
Acquired
LCAT deficiency
Abetalipoproteinemia
Immune mediated
Mechanical, thermal, chemical damage
Infectious agents
is defined as one in which the life span of normal red cells would be shortened if they were transfused to a patient under investigation but the patient’s red cells would survive normally if given to a normal recipient (i.e. abnormal environment factors that damage normal red cells)
EXTRINSIC DEFECT
is one in which the patient’s erythrocytes would not survive normally when transfused to a normal recipient (the erythrocytes themselves are defective)
INTRINSIC DEFECT
Hemolytic anemia are often due to alterations in __ (either DEFICIENCY or DEFECTIVENESS)
STRUCTURAL PROTEINS
forms dimmers linked end-to-end to form tetramers
Spectrin
links together spectrin dimers
Actin
Mediates the spectrin:actin linkage
an integral membrane protein
Protein 4.1 –
Protein 3 –
binds the spectrin fiber
Ankyrin –
Is a hemolytic disorder characterized by numerous MICROSPHERIC erythrocytes in the blood film
Autosomal dominant inheritance and therefore manifests in heterozygotes
HEREDITARY SPHEROCYTOSIS
Confirmatory test for HS
OSMOTIC FRAGILITY TEST
MCV is normal but MCHC is increased
HEREDITARY SPHEROCYTOSIS
The _ hemolytic indicators of HEMOGLOBINEMIA, HEMOGLOBINURIA and HEMOSIDERINURIA DO NOT APPEAR IN !
intravascular
HEREDITARY SPHEROCYTOSIS
Is a heterogenous group of disorders characterized by large number of elliptocytes on the blood film
HEREDITARY ELLIPTOCYTOSIS
Protein membrane defects seen in HE:
Deficiency in Protein 4.1 (also called )
Deficiency in s__ interaction
Defective ankyrin-Protein 3 interactions (aka )
Spherocytic HE
spectrin dimer-dimer
Atypical HE
The mechanism of hemolysis involves:
Membrane loss
Decreased red cell “deformability”
Shortened red cell survival due to splenic destruction
HE
Is an extremely rare hemolytic disorder characterized by extreme anisocytosis and micropoikilocytosis
HEREDITARY PYROPOIKILOCYTOSIS
Are a heterogenous group of red cell disorders caused by increased membrane lipids, particularly phosphatidylcholine
HEREDITARY STOMATOCYTOSIS (HYDROCYTOSIS) and HEREDITARY XEROCYTOSIS (CELL DEHYDRATION)
Enzymopathies in EM pathway are referred collectively as
CONGENITAL NONSPHEROCYTIC HEMOLYTIC ANEMIAS
Is responsible for AEROBIC GLYCOLYSIS which generates 10% of the energy of the cell
THE PENTOSE PHOSPHATE PATHWAY or HEXOSE MONOPHOSPHATE SHUNT
leads to a marked reduction in ATP production, whicg is necessary for the maintenance of the membrane Na-K pump.
PK deficiency
Screening test for PK Deficiency and G6PD Deficiency
AUTOHEMOLYSIS TEST
– Autohemolysis is slightly to moderately increased but is partially corrected by glucose.
Seen in:
G6PD deficiency
HS
Unstable Hb Disease
TYPE I
Autohemolysis is greatly increased and glucose has no effect, however, ATP corrects the hemolysis. Seen in Pyruvate kinase deficiency.
TYPE II
Autohemolysis is greatly increased but can be corrected either by glucose or ATP. This pattern is also seen in triose phosphateisomerase deficiency
HEREDITARY SPHEROCYTOSIS
is the MOST COMMON enzymopathy associated with hemolysis
G-6-PD Deficiency
When G6PD is deficient, red cells cannot generate sufficient _ to detoxify _. Hemoglobin is oxidized to __ (Fe+3). Heme is liberated from globin. And globin denatures, forming _ . attach to membrane sulfhydryl groups, inducing cell rigidity. Lysis eventually occurs even before reaching the spleen.
GSH
peroxide
methemoglobin
HEINZ BODIES
protects enzymes and hemoglobin against oxidation by reducing hydrogen peroxide and oxygen radicals.
REDUCED GLUTATHIONE (GSH)
This screening test INDIRECTLY detects NADPH generation by G6PD. This test is sensitive and can detect G6PD deficiency even in the presence of hemolysis
+ g6pd
METHEMOGLOBIN REDUCTASE TEST
Little or no fluorescence
This test measures the ability of normal cells to detoxify hydrogen peroxide when incubated with ascorbate.
+ g6pd
ASCORBATE CYANIDE TEST
brown color
In this group of disorders, red cell survival is affected by abnormalities in lipid metabolism. 2
HEREDITARY PLASMA CONSTITUENT ABNORMALITIES
Abetalipoproteinemia
Lecithin-Cholesterol Acyltransferase (LCAT) deficiency
Also known as Hereditary Acanthocytosis
ABETALIPOPROTEINEMIA
ABETALIPOPROTEINEMIA
Malabsorption of fat
Retinitis pigmentosa
Neurologic damage
Acantho
A rare inherited disorder characterized by mild normocytic, normochromic anemia
Found in Scandinavian families
LECITHIN-CHOLESTEROL ACYL TRANSFERASE (LCAT) DEFICIENCY
