1/4 Anemia2 - Wondisford Flashcards
globin gene cluster
which chromosome?
chromosome 11: 1epsilon, 2gamma, 1alpha, 1beta
chromosome 16: 2zeta, 2alpha
alpha thalassemia
pathophys
prevalence in pops
of alleles deleted → disease state
two alpha genes on each ch16 → 4 genes total
alpha-globin gene del = decr alpha globin synth
- cis del: Asian pops
- trans del: African pops
1 allele del → no anemia
2 alleles → mild microcytic anemia
3 alleles → HbH disease
- v little alpha globin
- excess beta blobin (HbH)
4 alleles → no alpha globin
- no alpha globin
- excess gamma globin (HbBarts) (bc youre a baby here)
- incompatible with life → causes hydrops fetalis
- incr likelihood in Asians
beta thalassemia
number of genes
nomenclature
prevalence
2 types
signs/sx
one beta gene on each ch11 → 2 total
nomenclature
- beta+ = mutant
- beta0 = absent
prevalent in Mediterranean and AfAm pops
beta thalassemia minor (heterozygote)
- beta/beta+: diag confirmed by incr HbA2 (>2.5%) and/or HbF (>1%)
beta thalassemia major (homozygote)
- beta0/beta0 (beta chain absent, >95% HbF)
- beta+/beta+ (>70% HbF)
- severe anemia w target cells requiring blood transfusion
- marrow expansion (crew cut on skull xray)
- chipmunk facies
- incr risk of parvovirusB19-induced aplastic crisis
- HbF is protective in infant → disease only becomes symptomatic after 6mo
adult Hb electrophoresis
describe diffs seen in…
- beta thal minor
- beta thal major
- alpha thal
beta thal minor
- drop in HbA
- incr in HbA2
beta thal major
- large drop in HbA
- incr in HbA2
- overflow incr in HbF
alpha thal
- drop in all types of Hb using alpha globin
- incr in HbBart
sideroblastic anemia
causes
why are there ring sideroblasts in sideroblastic anemia?
what tx should you always try?
cause: defect in heme synthesis
- alcohol (most common)
- myelodysplastic syndrome
- genetic
- X linked defect in deltaALA synthase
- vitB6 def
- Cu def
- lead poisoning
sx:
- high serum Fe (bc not used to incorp into heme)
- high ferritin
- low TIBC
- high saturation
- basophilic stippling (due to retained rRNA)
treatment
- pyridoxine (B6: cofactor for deltaALA synthase)
why?
iron is stuck in mitochondria!
iron present but not being incorporated into heme
tx: try B6 bc you might jump start heme production with a high dose of the cofactor
lead poisoning
type of sideroblastic anemia
pathophys: lead inhibits ferrochelatase and deltaALAdehydratase
sx: ringed sideroblast and basophilic stippling. LEAD
- Lead Lines on gigivae (Burton lines) and long bones
- Encephalopathy and Erythrocyte basophilic stippling
- Abdominal colic and sideroblastic anemia
- Drops: wrist and foot drop
treatment: chelation with dimercaprol and EDTA
normocytic, nonhemolytic anemias
anemia of chronic disease
- pathophys, progress
- associated conditions
- lab findings
- tx
inflammation → increased hepcidin synth (liver)
- Fe transport inhibited →
- decr release of iron from macrophages
- decr iron absorption from gut
can become microcytic (as in iron def anemia)
associated with conds like rheumatoid arthritis, SLE, neoplastic disorders, chronic kidney disease
labs
- decr serum iron, TIBC, % sat
- incr ferritin
treatment
- epo (for chronic kidney disease only)
normocytic nonhemolytic anemias
aplastic anemia
caused by destruction of myeloid stem cells due to…
- radiation and drugs (benzene, chloramphnicol, alkylating agents, antimetabolites)
- viruses (parvovirus B19, EBV, HIV, HCV)
- Fanconi anemia (DNA repair defect)
- idiopathic primary stem cell defect
lab/sx:
- pancytopenia
- normal cell morpho, but hypocellular bone marrow with fatty infiltration
- dry bone marrow tap
- fatigue, malaise, pallor,
- purpura, petechiae, mucosal bleeding
- infection
treatment:
- immunosuppressives
- allogenic bone marrow transplant
- RBC/platelet transfusion
- bone marrow stim
normocytic, normochromic anemia:
hemolytic anemias are classified according to cause of hymolysis (intrinsic vs extrinsic) and location of hemolysis (intravasc vs extravasc)
- don’t always go together
intravascular vs extravascular hemolysis
- sx
- causes
intravascular hemolysis
- sx
- decresaed haptoglobin
- increased LDH and some increase in unconj bilirubin
- hemoglinuria
- hemosiderinuria
- causes
- paroxysmal nocturnal hemoglobinuria
- G6PD deficiency
- micro/macro angiopathic anemia
- malaria
extravascular hemolysis
- sx
- macrophage in spleen clears RBCs
- incr LDH plus large increase in unconjugated bilirubin (from heme breakdown in macrophages)
- jaundice BUT NO hemoglobinuria, hemosiderinuria
- causes
- RBC membrane defect
- RBC enzyme defect
- hemoglobinopathies (S and C)
- autoimmune
intravascular vs extravascular hemolysis
graphic
summary2
