120814 hemoglobin disorders

Question 1

thalassemias

Answer 1

under production of STRUCTURALLY NORMAL globin chains

Question 2

HbF is composed of

Answer 2

alpha2gamma2

Question 3

routine electrophoresis–how does it work for assessing for hemoglobin structural abnormality?

Answer 3

use alkaline and acid buffers. depending on the hemoglobin’s net charge, migrates differently.

Question 4

HPLC-how does it work for assessing for Hb structural abnormality?

Answer 4

lyse RBCs in whole blood

hemoglobins are adsorbed onto resin particles in column and elute at different times based on affinity for resin

Question 5

factors affecting concentration of HbS

Answer 5

percent of hemoglobin S of total hemoglobin

total hemoglobin concentration in the red cells (MCHC)–it’s increased in states of cellular dehydration and decreased when there is coexistent thalassemia

Question 6

time dependence of sickling for HbS

Answer 6

importance of transit time of red cells through low O2 microvasculature

sickling enhanced in anatomic sites with sluggish flow (spleen and bone marrow)

Question 7

clinical settings predisposing to sickling for HbS

Answer 7

hypoxia
acidosis
dehydration
cold temperatures
infections

Question 8

sickling of RBC is reversible or irreversible?

Answer 8

reversbiel but after multiple sickling/unsickling cycles, membrane damage results in an irreversibly sickled cell

Question 9

effects of RBC sickling

Answer 9

chronic hemolysis
microvascular occlusion with resultant tissue hypoxia and infarction (due to sticky SS red cells that result due to membrane damage)

Question 10

clinical manifestations of sickle cell anemia

Answer 10

severe anemia
acute pain crises
auto splenectomy
acute chest syndrome (pulmonary event)
strokes
aplastic crisis (usually due to parvovirus B19 infec)

Question 11

more clinical manifestations of sickle cell anemia

Answer 11

infections
liver damage
splenic sequestration crisis
megaloblastic anemia
growth retardation
bony abnormalities
renal dysfxn
leg ulcers
cholelithiasis

Question 12

blood findings for SS disease

Answer 12

chronic anemia (5-11 g/dl Hb)
increased bilirubin
sickled cells, target cells, polychromasia
increased reticulocytes
normal MCV
post splenectomy changes in adults

Question 13

hemoglobin SC disease

Answer 13

compound heterozygous state (have HbS and HbC genes)

hemoglobin C results from glu to lys substitution

Question 14

HbS is

Answer 14

two alphas, two sickle betas

Question 15

S-trait

Answer 15

normal RBC survival

labs: 60% HbA, 40% HbS

Question 16

HbC disease

Answer 16

CC homozygous
mild to moderate hemolytic anemia. often asymptomatic

NOT a sickling disorder–cells are abnormally rigid and dehydrated

Question 17

thalassemias in general–their morphology?

Answer 17

microcytic, hypochromic anemias

Question 18

severity of hematologic manifestations in thalassemias is due to

Answer 18

degree of chain imbalance (excess normally produced gloin chains accumulate and cause intramedullary cell death or decreased RBC survival)

Question 19

beta thal major

Answer 19

both beta alleles affected

excess of normal alpha chains precipitate in normoblasts and erythrocytes, causing intramedullary cell death and decreased RBC lifespan

severe anemia–Hb 2-3 g/dL

Question 20

blood smear for beta thalassemia major

Answer 20

target cells
hypochromic RBCs
nucleated RBCs

bizarre morphology overall

Question 21

lab features for beta thal minor

Answer 21

mild or no anemia (Hb over 10)
microcytosis (50-70 fl)
mild anisopoilocytosis (scattered target cells)
basophilic stippling
elevated HbA2 is USED TO DIAGNOSE (3.5-7%)

Question 22

alpha thalassemia variants

Answer 22

silent carrier

alpha thal trait (2 genes deleted)

hemoglobin H disease (chronic hemolytic anemia. HbH doesn’t transfer O2 and is useless)

hydrops fetalis