RBC and Bleeding Disorders III Flashcards
prognosis of sickle cell
90% survive 20yo
50% survive 50yo
tx of sickle cel
DNA synthesis inhibitor
hydroxyurea
increases HbF
chromosome 16
2 genes for alpha chains
chromosome 11
1 gene for beta chains
problems with thalassemias
Hg deficiency
AND the excess of other globin chain
decreased red cell production and lifespan
-NOT hemolysis
mediterranean basin
thalassemia syndromes
also, middle east, tropical africa, india, asia
protection against malaria
heterozygotes for sickle cell and thalassemias
B0
absent beta globins
chain termination mutations
B+
reduced beta-globins
splicing mutations and promoter region mutations
beta-thal major
two thal alleles
-B0 or B+
beta-thal major clinical
severe, requires blood transfusions
beta-thal
mainly point mutations
alpha-thal
gene deletions
beta-thal intermedia
variable thal genes
some have alpha-chain defect - less severe bc less imbalance of alpha-beta
beta-thal intermedia clinical
severe but no transfusions
beta-thal minor
one thal allele and one normal allele
beta-thal minor
asymptomatic with mild or absent anemia
RBC abnormalities
silent carrier alpha-thal
1/4 alpha chains thalassemia
asymptomatic with no RBC abnormality
alpha-thal trait
2/4 alpha chains thalassemia
asymptomatic
HBH disease
3/4 alpha chains thalassemia
severe - but not regular transfusions
hydrops fetalis
4/4 alpha chains thalassemia
lethal in utero without transfusions
hypochromic.microcytic RBCs
beta-thal
beta-thal pathology
diminished survival of RBCs
-due to imbalance of alpha-beta
unpaired alpha chains precipitate
membrane damage - most problems
apoptosis
severe beta-thal
70-85% of RBC suffer fate of alpha chain inclusion - ineffective erythropoiesis
RBCs - splenic sequestration and extravascular hemolysis
extensive EMH, cachexia, suppression of hepcidin (too much Fe absorbed)
immigrants from mediterranean
thalassemia
beta-thal major clinical
6-9 months after birth - anemia
-when Hg goes to HbF to HbA
major Hg - HbF
HbA2 normal or low
requires exchange transfusions
beta-thal major prognosis
wihout transfusions - death
growth retardation, enlarged cheekbones and distorted
cardiac disease
iron overload in beta-thal major
tx with iron chelators
survival - third decade
crew cut xray
with beta-thal major
target cells
beta-thal major
Hg collects in center of cell
basophilic stippling
beta-thal major
beta-thal minor
more common than beta-thal major
asymptomatic with mild anemia
hypochromic, microcytic
basophilic stippling
target cells
increased HbA2 - alpha2delta2
normal HbF
beta-thal minor resembles
like iron deficiency
-implications for genetic counseling
diagnosis of beta-thal minor
look at serum Fe, TIBC, ferritin levels
also - HbA2 increase is diagnostically issue
HbA2
alpha2delta2
hemoglobin barts
gamma-4 tetramers
in newborns
hydrops fetalis - 0/4 alpha chains present
HbH
beta-4 tetramers
free beta and gamma chains
more soluble
-so the hemolysis is less severe in alpha-thal than beta-thal
hydrops fetalis
increased O2 affinity
-fetal distress - third tromester
Hg barts - gamma4
can survive with intrauterine transfusion
