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Flashcards in Hemoglobinopathies Deck (51):
1

hemoglobinopathy definition

disorder involving hemoglobin

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disorder involving heme

porphyria

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globins expressed embryonically

epsilon

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globins expressed fetally

gamma, alpha (HbF)

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globins expressed in adults

alpha, beta (HbA) & alpha, gamma (HbA2)

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what types of deletions tend to affect the alpha globin?

deletional mutations leading to zero condition (no production)

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what types of deletions tend to affect the beta globin?

nondeletional mutations which tend to lead to plus mutations (decreased production)

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types of nondeletional mutations

transcription, mRNA processing, transport, translation, mRNA stability, protein function mutations

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composition of typical adult hemoglobin

two alpha, two beta globins and heme

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structural hemoglobinopathies

qualitative defects in hemoglobin function

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examples of structural hemoglobinopathies

sickle hemoglobins, low/high O2 affinity, unstable hemoglobins, methermoglobins

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thalassemia definition

quantitative defects in hemoglobin production (Hb made is normal, just not enough is made)

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types of thalassemias

alpha, beta, hereditary persistence of fetal, fusion hemoglobins

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most important thing to know about severity of thalassemia******

*****the degree of alpha/beta chain imbalance predicts the severity of the phenotype********

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characteristics of thalasemmia anemia

microcytic, hypochromic

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alpha thalassemia

deficiency in HbA (alpha/beta) with excess HbH (beta/beta)

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HbH

beta homotetramer hemoglobin corresponding with alpha thalassemia. soluble and nontoxic

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alpha thalassemia trait

-a/-a or --/aa. quite mild (slightly low levels of Hb, and slightly small MCV)

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HbH disease

--/-a. high levels of HbH present. still quite mild symptoms

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hydrops fetalis

--/--. complete alpha thalassemia. fatal before birth

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most common alpha thalassemia in blacks

-a/-a. common but not an issue for offspring

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most common alpha thalassemia in asians

aa/-- common, which can lead to hydrous fetalis in offspring

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beta thalassemia

deficiency in Hb (alpha/beta) and excess alpha homotetramers, which precipitate and are toxic!

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beta thalassemia minor (trait)

B/B* (one of two genes is defective). decreased Hb & MCV. Increase HbA2 as compensation

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beta thalassemia intermedia

B+/B* (two defective genes with one mutation being milder) or B+/B+ (two mild mutations). vast phenotypes, anemia, low MCV

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beta thalassemia major

B*/B* (two defective genes). very anemic, very low MCV, 10% HbA2, 90% HbF as compensation.

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characteristic most indicative of beta thalassemia?

increased HbA2 levels!

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clinical presentation of severe beta thalassemia

family history, ethnic background, poor growth/development, jaundice, frontal bossing, splenomegaly, hypochromic/microcytic anemia with targeting, normal iron levels, INCREASED HBA2

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consequences of alpha homotetramer precipitation

erythroid progenitor membrane damage=ineffective erythropoiesis & RBC membrane damage=accelerated removal=hemolytic anemia
--->both lead to profound anemia

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consequence of ineffective erthyroid mass due to profound anemia in beta thalassemia?

compensatory erythropoiesis (marrow from atypical locations, frontal bossing) & extra medullary erythropoiesis (splenomegaly)

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most common causes of microcytic anemia

iron deficiency & thalassemia

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distinguish iron deficiency vs beta thalassemia

TEST IRON LEVELS

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DIAGNOSE: Hb=9, MCV=74, Ferritin=2

Iron deficient anemia

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DIAGNOSE: Hb=11, MCV=65, Ferritin=Nl

thalassemia

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DIAGNOSE: A=94%, A2=5%, F=0%

increased A2=beta thalassemia minor (major would have higher A2, like 10% and increased F)

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DIAGNOSE: Hb=3.5, MCV=57, Ferritin=1822

thalassemia

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DIAGNOSE: A=0, A2=10%, F=90%

beta thalassemia major

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treatment for thalassemia

PRBC transfusion or chelating agents (remove iron), bone marrow transplant

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genetic basis of sickle cell disease

single missense mutation that results in Glu-->Val substitution in beta globin

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cause of sickle shape?

when deoxygenated, Hb assembles into long polymer fibers that destroy RBC membrane structure.

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theories on pathophysiology of sickle disease

log jam model, RBC dehydration, cellular adhesion, reduced NO bioavailability

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treatment for chronic sickle cell disease

hydroxyurea=inducer of fetal gamma glob in (no hydrophobic site for polymerization). bone marrow transplant

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blood characteristics of sickle cell disease

moderate anemia, normocyti/normochromic RBCs, drepanocytes (sickle)

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AA Hb electrophoresis

A=97, A2=<3, F=0, S=0

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AS Hb electrophoresis

A=60, A2<3, F=0, S=40 (40/60 RULE)

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SS Hb electrophoresis

A=0, A2<10, S=90

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DIAGNOSE: A=40, A2=5, F=0, S=60

co inherited beta thalassemia with sickle cell (B+ reducing levels of A, Bs increasing levels of S)

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DIAGNOSE: A=80, A2=1.5, F=0, S=20

co inherited alpha thalassemia with sickle cell

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DIAGNOSE: Hb=14, MCV=85, A=59, A2=2, F=0, S=39

sickle cell trait

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DIAGNOSE: Hb=8, MCV=88, A=0, A2=2.5, F=2, S=96

sickle cell disease

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DIAGNOSE: Hb=11, MCV=72, ferritin=477, A=10, A2=7, F=7, S=76

coinherited beta thalassemia and sickle cell in beta globin (Bs/B+)