anemia pt 1 Flashcards
what makes someone anemic?
female
- hgb <12g/dL
- hct <36%
male
- hgb <13.6 g/dL
- hct <41%
3 major causes of anemia
- decreased in RBC production
- increased destruction of RBC
- increased blood loss
2 classifications of hemolytic anemia
- intravascular - RBCs lyse within BLOOD VESSELS
- extravascular - RBCs are destroyed within ORGANS
what classification of hemolytic anemia would you see:
- large amounts of hgb released into circulation - decrease in haptoglobin; possible hemoglobinuria
- decreased iron over time
- schistocyte formation
intravascular hemolytic anemia
what classification of hemolytic anemia would you see:
- minimal hgb release in circulation - haptoglobin may or may not decrease
- iron is recovered and stored
- spherocyte formation
extravascular hemolytic anemia
for extravascular hemolytic anemia, RBC is destroyed in the ?
spleen (mostly)
liver
PE findings for hemolytic anemia
skin - pallor, jaundice
abd - +/- spleen enlargement
urine - red/brown discoloration (intravascular hemolysis)
lab findings for hemolytic anemias
hgb - normal or reduced
MCV - increased
reticulocytes - increased
bilirubin - increased (unconjugated)
LDH - increased
haptoglobin - decreased (intravascular)
what can falsely elevate haptoglobin lvls
inflammatory markers
causes of hemolytic anemia
- structural
- hereditary spherocytosis - hemoglobinopathies
- thalassemias
- sickle cell disease - metabolic
- G6PD deficiency - immune-related
- autoimmune hemolytic anemia (AIHA)
- paroxysmal nocturnal hemoglobinuria (PNH)
- hemolytic disease of the newborn (HDN)
cause of hereditary spherocytosis
abnormal formation of proteins in the RBC membrane
inherited, mainly autosomal dominant
pathology of hereditary spherocytosis
abnormally shaped RBCs (rounded) = trap in small red pulp fenestrations = phagocytic destruction
lab findings of hereditary spherocytosis
hgb/hct - variably decreased
reticulocytes - increased
MCHC - INCREASED
MCV - normal or low
haptoglobin - normal or low
peripheral blood smear - spherocytes
coombs testing - should be negative
only one that can cause INCREASED MCHC in microcytosis/normocytosis
treatment of hereditary spherocytosis
- ALL get folic acid
- Transfusion - if severe
- splenectomy - DEFINITIVE TX
- moderate - delay until after 5yo or puberty
- mild - observe
- antipneumococcal vax
3 types of hemoglobin
- hbA - 97-99% of Hb - “adult” hgb
- hbA2 - 1-3%
- hbF - <1%
chromosome 16 has 2 copies of ?
alpha-globulin gene - 4 total
chromosome 11 has 1 copy of ?
beta-globulin gene - 2 total
also has copies of delta-globulin and gamma-globulin gene
cause of alpha thalassemias
gene deletion = reduced alpha-chain synthesis
pathology of alpha thalassemias
- more small, “pale” (low hb) RBCs
- excess beta chains precipitate = damaging RBC membrane = hemolysis in marrow and splenic vessels
demographics of alpha thalassemias
SE asians and chinese descent
mediterranean or african descent
Hb electrophoresis of alpha thalassemias would present ?
normal - equal proportion of hbA, hbA2, hbF
lab findings for alpha thalassemias
hgb/hct - normal (carrier) or decreased
RBC - increased
MCV - decreased - very tiny
reticulocyte - increased or normal
MCH - decreased
inclusion bodies - in HbH disease
how would the electrophoresis present in alpha thalassemia
carriers, alpha talassemia minor - normal
HbH disease - presence of HbH band
3 normal alpha-globulin genes result in ?
carrier = alpha thalassemia MINIMA
normal lab values (HCT, MCV)
2 normal alpha globulin genes result in ?
alpha thalassemia MINOR
HCT - 28-40%
MCV - 60-75%
1 normal alpha globulin gene results in ?
hemoglobin H disease (HbH)
has 4 beta-chains = little to no use for O2 transport
HCT - 22-32%
MCV - 60-70%
no normal alpha globulin genes result in ?
hydrops fetalis
die in utero
describe the peripheral smear findings of alpha thalassemia trait
- hypochromatic, microcytic cells
- target cells
describe the peripheral smear findings of HbH
- hypochromatic, microcytic cells
- target cells
- poikilocytosis
- sometimes some normal RBC bc of transfusions
treatment for alpha thalassemia
- minima
- no treatment - minor
- usually no treatment; genetic counseling
- must monitor iron overload - chelation - HbH
- folic acid supplement
- avoid iron supplements and oxidative drugs - MONITOR IRON
- may need transfusion regularly
- splenectomy if severe or too frequent transfusions - hydrops fetalis
- termination
cause of beta thalassemias
gene point mutation = reduced beta-chain synthesis
types of betathalassemias
- beta+ - reduced beta-chain synthesis
- beta0 - absent beta-chain synthesis
how would the electrophoresis of beta thalassemias present?
increased proportion of HbA2 and HbF
(HbF > HbA2)
demographics of beta thalassemias
mainly mediterranean descent
can be seen in african and asian descent
pathology of beta thalassemias
- more small, “pale” (low Hgb) RBC
- excess alpha chains precipitate = hemolysis in marrow, spleen, liver
- alpha chains = inclusion bodies = damaged erthyroid precursors (intramedullary)
- surviving RBCs = inclusion bodies = short lifespan (extramedullary)
lab findings of beta thalassemia
hgb/hct - decreased
RBC - increased
MCV - decreased
reticulocyte - increased
MCH - decreased
exam findings of beta thalassemia
“chipmunk facies”
thinning of long bones
pathologic fracture
failture to thrive
describe the peripheral smear findings of beta thalassemia minor
hypochromic, microcytic cells
target cells
describe the peripheral smear findings of beta thalassemia intermedia
hypochromic, microcytic cells
target cells
poikilocytosis
describe the peripheral smear findings of beta thalassemia major
hypochromic, microcytic cells
target cells
poikilocytosis
nucleated RBC
treatment for beta thalassemia including definitive tx
- minor
- no tx; genetic counseling
- monitor iron overload - intermedia
- genetic counseling
- avoid iron supplements - may need if secondary condition causes iron deficiency
- may require transfusion
- monitor iron overload - major
- frq transfusion-dependent
- avoid iron supplements
- splenectomy
- luspatercept - promotes RBC production by interfering with TGF-B signaling
- bone marrow transplant - ONLY DEFINITIVE TX
sickle cell disease is an ____ ____ inherited disease
autosomal recessive
does NOT affect a sex more than the other*
cause of sickle cell disease
abn substitution of an amino acid in the beta chain (betaS)
for sickle cell, if you are heterozygous it would be ____, while homozygous would be _____
sickle cell trait
sickle cell anemia
demographics of sickle cell disease
African americans
1 in 400 black children
also mediterranean, latin, and native american descent
what % of African Americans make up carriers in the US
8%
pathology of sickle cell disease
unstable HbS polymerizes = sickled shaped = vaso-occlusive episodes
“stick” to endothelium
vasoocclusion = ischemia, pain, end-organ damage
what sequesters and destroys sickled RBCs?
spleen
what triggers sickle cell disease?
anything stressful!
hypoxemia, acidosis, infection, excessive exercise, abrupt temp changes, anxiety/stress
a pt with sickle cell disease would show what in their hemoglobin electrophoresis?
abnormal proportions of HbA, HbA2, HbF
presence of HbS band
Howell-Jolly inclusion bodies would be seen in ___
sickle cell anemia
clinical presentations for sickle cell trait
often asymptomatic
can have s/s during physical stress - high altitude, heavy exercise, dehydration
when do s/s for sickle cell disease appear?
around 6 months old
clinical presentations for sickle cell anemia
- poorly healing LE ulcers (10+ y/o)
- dactylitis
- vision changes, retina problems
- splenomegaly (<3 y/o)
- hyperdynamic precordium
clinical presentation of sickle cell crisis
- ischemic injury to 1+ organs
- sudden pain that lasts from hrs to wks
- fever, tachycardia
- MC locations - abd, bones, joints, soft tissues
– <18m - hands/feet
– children/teens - long bones of arms/legs
– adults - vertebrae
how do you treat sickle cell anemia/what are the ways
- avoid triggers
- hypoxemia
- temp changes
- dehydration
- acidosis
- stress - supportive
- Folic acid
- vaccinations
- ACE inhibitors
- omega-3 fatty acids
- pain management
- abx = prophylactic PCN daily until age 5, then optional - disease-modifying meds - decreases vasoocclusive episodes
- hydroxyurea
- crizanlizumab
- l-glutamine
what is the mainstay medication of sickle cell anemia treatment? what SE must you address
hydrourea
bone marrow suppression
- can cause skin ulcers
- increase cancer risk
-teratogenic
an acute sickle cell crisis treatment is…
HOP - hydration, oxygenation, pain control
- exchange transfusion - vasoocclusive crises, pain crises, other severe sequelae
- splenic sequestration crisis (disprop. amount of blood sequestered in spleen)
– splenectomy to prevent recurrence
definitive tx for sickle cell anemia
stem cell transplant
main cause of G6PD deficiency is…
enzyme deficiency
x-linked recessive!!
G6PD deficiency is commonly seen in…
African american MALES (X-linked recessive)
also in Asian and mediterranean descent
what anemia is seen when RBCs are vulnerable to oxidative stress and forms Heinz bodies
G6PD deficiency
Splenomegaly is usually not seen in G6PD deficient pts because…
it is an episodic hemolytic anemia
what are the 3 major triggers of G6PD deficiency
- infections
- foods - FAVA BEANS
- medications - ABX (sulfas, quinolones, nitrofurantoin), Azo, aspirin
dark urine can be seen in G6PD deficiency because …
it is INTRAVASCULAR
a peripheral smear with bite cells, blister cells, and Heinz bodies is seen in…
G6PD deficiency
avoiding oxidant drugs is a preventive measure for what anemia
G6PD deficiency
cause of autoimmune hemolytic anemia
- antibodies form against RBC antigens (igG)
- 50% idiopathic
- diseases - SLE, leukemia, lymphoma
autoimmune hemolytic anemia must be distinguished from…
drug-induced immune hemolytic anemia
- caused by abx (cephalosporins, PCNs, quinolones), methyldopa or levodopa, or NSAIDs
pathology of autoimmune hemolytic anemia
RBC tagged for destruction
spherocytes formation
what anemia can have complements tag RBC for destruction by Kupffer cells
autoimmune hemolytic anemia
how does IgM play a role in autoimmune hemolytic anemia
facilitates MAC-induced direct intravascular hemolysis
what type of hemolytic anemia can be triggered from warm or cold temperatures
autoimmune hemolytic anemia
difference between direct and indirect Coombs test
direct = RBC - reagent mixed with pt RBC
indirect = serum - pt serum is mixed with RBCs; reagent is added
marked microspherocytosis can be seen in ?
autoimmune hemolytic anemia
immunosuppression, comorbidities, and transfusions can be treatments for..
autoimmune hemolytic anemia
severe = splenectomy or transfusion
cause of hemolytic disease of newborns
maternal IgG to antigens on surface of fetal RBC
- fetal-maternal hemorrhage
- hydrops fetalis
positive direct Coombs test can be seen on who during hemolytic disease of the newborn
newborn
indirect = maternal
what is the preventive care for hemolytic disease of newborn
RhoGAM - prevents immune response to Rh+ blood in Rh- mother
an acquired genetic defect that leads to RBC lysis by complement
paroxysmal nocturnal hemoglobinuria
Free Hb from NH results in…
depleted NO
esophageal spasms, ED, renal damage, thrombosis
PNH is common during ?
first thing in AM and drop in blood pH overnight - improves throughout the day
episodic hemoglobinuria*
the diagnostic gold standard for PNH is…
flow cytometry
TX for severe or aplastic anemia from PNH
allogeneic hematopoetic stem cell transplant
TX for severe hemolysis or thrombosis from PNH
eculizumab
what supportive medication may reduce hemolysis for PNH
corticosteroids
acute anemia due to blood loss is commonly caused by
direct RBC loss
- posthemorrhagic anemia
- external - trauma, postpartum hemorrhage
- internal - GI bleed, ruptured ectopic pregnancy, ruptured spleen, subarachnoid hemorrhage
chronic anemia due to blood loss is commonly caused by
depletion of iron stores = iron deficiency anemia
process of anemia due to blood loss
- hypovolemia - risk of organ hypoperfusion, CBC does not show anemia*
- anemia - compensatory mechanisms = hypovolemia resolves = CBC now shows anemia
- recovery - marrow replaces lost RBC with new, transient reticulocytosis
compensatory mechanisms during anemia due to blood loss
vasoconstriction
fluid retention
shift of fluid from extravascular to intravascular
IV fluids