Hemoglobinopathies and Thalassemia Flashcards Preview

Hematology Module 2 > Hemoglobinopathies and Thalassemia > Flashcards

Flashcards in Hemoglobinopathies and Thalassemia Deck (53):
1

clinical manifestations thalessemia

anemia, chronic hemolysis, microcytic hypochromic, ineffective erythropoesis. Splenomegaly, functional hyposplenism.

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extramedullary erythropoesis in thal causes

masses large enough to cause compression syndromes.

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lab findings thal

decreased MCV, hemoglobin, MCH, MCHC, microcytic hypochromic, presence high affinity hemoglobins, increased EV hemolysis, extramedullary hematopoeisis.

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Mentzer index

differentiate thal from IDA. Divide MCV / RBC #. If < 13 favors thal. If > 13 favors IDA. Iron studies should also be performed. Perform hemoglobin electrophoresis. Sequencing for hemoglobin types, dot blot assays first.

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alpha gene genetics

2 a genes located on each of chromosome 16. A2 located upstream and produces 2-3 times more mRNA than A1 downstream.

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all 4 alpha genes mutated

hydrops fetalis

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3 alpha chains mutated

HBH disease

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deletion 2 genes

thalassemia minor.

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deletion 1 gene

silent carrier.

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difference hemoblobinopathies thal

thal RBC count increased over what is expected, opathies normocytic normochromic, thal microcytic microchromic. sickles cells and crystals in opathies. Solubility test + in opathies, - in thal. Retic increased more in opathies. `HBH HB barts present.

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Gamma clobin tetramers

barts

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Deletional more common in

alpha genes

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non deletional more common in

beta chains. ie promoter nonsense, stop codon, splice site.

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beta gene genetics

located on chromosome 11 only one beta gene from each parent

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target cells

increase in beta thalassemia major. anemia is also more severe.

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A and F hemoglobin relationship in thalassemia

as aanemia sd severity increases from minor to major, A decreases F increases. Can be seen on electrophoresis.

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increase in F

increased oxygen affinity for F decreases delivery to tissues.

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Beta thalassemia

increased alpha chains cause precipitation, damage rbc membrane, cause ineffective erythropoeisis and IV EV destruction, SPLENOMEGALY, INCREASE EPO, EXTRAMEDULLARY ERYTHROPOEISIS. INCREASE IRON, TOXICITY.

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target cells in thal due to

decrease in hemoglobin without corresponding decrease in membrane.

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reticulocyte count lower than expected in thal due to:

ineffective erythropoeisis

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hb constant spring

alpha chain elongated by 31 amino acids. homozygs mild anemia hetero asymptomatic.

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hb lepore

hybrid beta-delta chain fusion. Alpha chains have nothing to associate with cause hemolysis like beta thal.

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Hereditary persistence of fetal hemoglob

increase in gamma chains to compensate for absence of beta dlta chains. HBF common. Mostly asymptomatic.

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HBS Pathology

GLU-> Val mutation on surface causes less polar and less soluble in deoxy state. Reversible on oxygenation. Delays means most blood cells do not sickle, but sickle in spleen kidney and other hypoxic acidic

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HBA

A2B2 normal adult

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Gower 1

psi epsilon embryonic

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Gower II

A epsilon embryonic

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Portland

Psi2 gamma 2 embryonic

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HBF

alpha 2 gamma 2

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HBA2

alpha2 delta 2

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Hemoglobin chain ovef maturation

switch from psi to alpha, and epislon (E) to gamma (F) to B(adult)

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test for hemoglobinopathies:

electrophoresis, HPLC PCR, solubility test, heat precipitation test, tests for Heinz bodies.

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Mutation for HB S, C and E

ALL GLUTAMIC ACID NEGATIVE CHARGE. S IS NON POLAR VAL, WHILE E AND C ARE POSITIVELY CHARGED LYS.

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HBS BLOOD SMEAR

NORMOCYTIC NORMOCHROMIC, SICKLE CELLS

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HBE BLOOD SMEAR

MICROCYTIC MICROCHROMIC, TARGET CELLS

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HBC

NORMOCYTIC AND CHROMIC RETICULOCYTOSIS TARGET CELLS

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SICKLE CELL DISEASE ASSOCIATED WITH

EV HEMOLYSIS. RPI 3-5 X TO COMPENSATE.

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HBS OXYGEN AFFINITY

LOWER. BUT POLYMERIZES LEADING TO PREMATURE DESTRUCTION.

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SICKLING HAPPENS UPON

DEOXYGENATION, REVERSES ON OXYGENATION. MORE PRONE TO OXIDATION. LEADS TO LOSS OF WATER, DESTRUCTION OF MEMBRANE LATTICE PROTEINS, DECREASES DEFORMABILITY, CATION PROTEINS, EV HEMOLYSIS.

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VASO OCCLUSIVE CRISIS

DEOXYGENATION, BLOCKAGE, REPEATED DEOXYGENATION FROM ANEMIC TISSUE AHEAD OF BLOCKAGE.

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AUTOSLPENECTOMY

EXTENSIVE EV HEMOLYSIS DECREASES OXYGEN TO SPLEEN, LEADING TO DECREASED FUNCTION.

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HYDROXYUREA BOOSTS

HBF PRODUCTION

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HEMOGLOBIN CRYSTAL

MILD TO MODERATE, NO VASOOCCLUSIVE CRISIS. HEMOGLOBIN CRYSTALS FORM. HB S / C HETEROZYGOUS IIS INTERMEDIATE BETWEEN BOTH DISEASES. mORE S BECAUSE S IS MORE NEGATIVELY CHARGED.

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HEMOGLOBIN E

MILD ASYMPTOMATIC ANEMIA.

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METHHEMOGLOBINEMIA

OXIDIZED HEMOGLOBIN IS METHHEMOGLOBIN, CANNOT BIND OXYGEN. kEPT REDUCED BY METHHEMOGLOBIN REDUCTASE.>1%.

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CAUSES METHHEMOGLOBINEMIA

ACQUIRED, REDUCTION PATHWAY OVERWHELMED.
OR CONGENITAL. DEFECT IN PATHWAY, OR STRUCUTURAL ABNORMALITY, HBM.

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HBM CAUSES

PSUEDOCYANOSIS.

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HBH

BETA TETRAMERS

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HB BARTS

GAMMA TETRAMERS

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CHRONIC HEMOLYSIS IN HBH

PRECIPITATES OF HBH TRIGGER HEMOLYSIS

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BETA+

PARTIAL BLOCK OF BETA CHAIN SYNTHESIS

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BETA0

FULL BLOCK OF BETA CHIAN SYNTHESIS.

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BETA THALASSEMIA BLOOD PICTURE

TARGET CELLS SCHISTOCYTES, RETICS LOWER THAN EXPECTED DUE TO INEFFECTIVE ERYTHROPOESIS