Anemia, Congen and Acquired Hemolytic, APSHO Flashcards
2 big categories for hemolytic anemia (and egs)?
Intrinsic to RBC (enzymopathies, hemoglobinopathies, membranopathies)
Extrinsic (Abs, toxins, mechanical, microangiopathic)
in addition to intrinsic and extrinsic, other way to differentiate hemolytic anemia?
Intravascular and extravascular
where does extravascular HA occur?
spleen and/or liver (RES)
what type of antibodies mediate intravascular vs extravascular hemolysis?
- Intravasc: IgM (occ IgG)
- Extra: IgGs that don’t fix complement
Do you expect LDH to be higher in intravascular or extravascular hemolysis? Do you expect haptoglobin to be lower in intravascular or extravascular hemolysis?
Intravascular for both
Lab-wise, how can you differentiate intra vs extravascular hemolysis?
In intravascular, see hemoglobinEMIA and hemoglobinURIA
4 egs of intravascular hemolysis?
Paroxysmal cold hemoglobinuria, cold agglutinin, PNH, valves
3 egs of extravascular hemolysis?
warm AIHA, hemolytic disease of the newborn, HS
symptoms/complications of hemolysis?
- Anemia
- Hydrops fetalis
- intrauterine growth retardation
- kernicterus (G6PD = #1 cause)
- blueberry muffin rash= skin extramedullary hematopoeisis
- prematurity
- neonatal hepatic failure
symptoms/complications of older kids/teens?
palor, fatigue, scleral icterus, jaundice, pulmonary htn, iron overload in transfused/non-transfused patients, GB stones, splenomegaly, low bone densiety, ednocrinopathies from Fe overload, extramedullary hematopoeisis in liver/spleen/mediastinal area, etc
General management of congen hemolytic anemia?
- Follow growth & dev
- determine baseline hgb and retics
- follow for splenomeglay
- educate fam re: gallstones, parvovirus b19 aplastic crisis
- monitor for pulmonary htn
- cholecystectomy if symptomatic gallstones
- monitor for fe overload and def
- folate supplementation/bone health
- RBC transfusion, intermittent vs. chronic..avoidance of over-transfusion in infancy; increased transfusions during preg
- splenectomy: partial or total, laparoscopic
denatured hgb…required supravital stain…evidence of oxidative damage as in G6PD def…what is this?
heinz bodies
nuclear remnants seen on ordinary Wrigh stein..eevidence of spleneoctomy and/or ineffective erythropo…what is this?
Howell-Jolly bodies
residual rna on polysomes on wright stain, seen with impaired translationi (thal, lead some enzymopathies)…what is this?
basophilic stippling
iron inclusions seen in wright stain, as in sideroblastoic anemia. what is this?
pappenheimer bodies
Give 10 causes of congenital HA
HBG-opathies -thal -SCD MEMBRANOPATHIES -HS -HE -HPP -Hereditary stomatocytosis -hereditary xerocytosis -Rh Null ENZYMOPATHIES -g6pd def -PK def -hexokinase def -aldolase def -phophofructose kinase def -pyrimidine 5' nucelotidase def
10 causes of acquired HA?
IMMUNE -warm AIHA -cold agglutinin -paroxysmal cold hemoglobinuria -transfusion rxn NON-IMMUNE HUS TTP DIC mech/heart valve Kasabach merritt paroxysmal nocturnal hemoglobinuria toxins/meds thermal burns wilson disease infection
HS defects (vertical interactions of membrane)?…spheres don’t deform as well in the spleen… 2
ankyrin, spectrin, actin
Hereditary elliptocytosis defects (horizontal interactions)? 2
band 3, glycophorins
HS inheritance?
AD
what’s the most common congen hemolytic aemia?
HS
most common mutation in HS?
ankyrin ANK1>band 3 SLC4A1>beta spectrin SPTB
recessie HS muation?
alpha spectrin
HS: will MCHC be high or low?
high (cellular dehydration)
other than spherocytes see what on HS smear?
polychromasia
3 ways to dx HS?
EMA bidning, incubated osmotic fragility, molecular dx
what makes HS patient more likely to have gallstones?
co-morbid gilbert syndrome
how does osmotic fragility test work?
incubate red cells in diff concentrations saline (0-0.9%)…with less saline concentration, cells take on water and lyse…normal cells lyse at 0.5%…HS cells lyse at HIGHER saline concentrations…degree of hemolysis detected by spectrophotometry…sens 80%
is osm frag a good test in neonates?
no…fetal cells relatively resistant to this test
EMA binding test=?
eosin-5-maleimide binding
explain EMA binding test
Eosin-based fluorescent dye binds to RBC membrane protiens, including band 3…see reduction of band 3 fluoresnce in pts with HS
sens and spec of EMA binding test?
sense 93-96%, spec 93-99%
reason for false + EMA binding?
CDA type II, South Asian Ovalocytosis, hereditary pyropoikilocytosis
benefits of full splenectomy vs. partial splenectomy in HS?
full: resolution of anemia, no risk of aplstic crisis/gallstones/hyper-hemolysis
partial: signficant imporvment in anemia, maintian some splenic function
cons of full splenectomy vs. partial in hS?
full: infections (encapsulated organissms, babesiosis, malaria); thrombosis (10%, due to decreased filtering capacity)
partial: splenic regrowth in 5-10%, compensated hemolysis so continued risk of aplastic crisis, gallstones, etc
splenectomy recommended for severe HS=?…no splenectomy rec’ed for mild HS=? in between = moderate
Severe: Hgb <60-80, requires transfusions…mild: Hgb>110, no sx
Hereditary elliptocytosis: most common mutation?
abnormal spectrin heterodimer: SPTA, SPTB
HE inheritance?
AD
symptoms in most HE pts?
usually asymptomatic
tx in HE?
usually no need…splenectomy helps if severe
2 subtypes of HE?
southeast asian ovalocytosis, alpha LELY
hereditary pyropoikilocytosis: most common abnormaltiy?
spectrin
HPP: inheritance?
AR…commonly HE SPTA1 mutation in trans to alpha LELY SPTA1
clinical findings in HPP? 3
blood smear: bizarre rbc shapes as in thermal burn
molecular testing of spectrin
MCV 55-74 (L)
HPP: prog?
severe hemolysis in early childhood, then HE later in life
2 types of stomatocytosis
hydrocytosis= overhydrated= low MCHC, xerocytosis= dehydrated= high MCHC
hydrocytosis: gene?
RHAG
xerocytosis in term osm fragility?
DECREASED (opp of HS, which is increased)
Mutations in xerocytosis?
PIEZO1, KCCN4
xerocytosis inheritance?
AD
xerocytosis ddx?
acute ehtanol intox, liver disease, rh null disease, tangier disease
complications of xerocytosis?
fe overload, marked increased risk of thrombosis of splenectomy!!!!! don’t do it!
hgb o2 dissoc curve: x-axis? y-axis?
x= pO2 (mmHg); y= % O2 sat
what pushes hgb o2 dissoc curve to left?
high pH, low temp, decreased 2,3 DPG
what pushes hgb o2 dissoc curve to right?
low pH, high temp, increaed 2,3 DPG
unstable hgbs inheritnace?
AD
clinical findings in unstable hgb?
blood smear: heinz bodies
hb electrophoreiss
urine: pigmenturia
sx: extravascular hemolysis, ineffective erythropoeisis
4 subtypes of unstable hgb?
Hb Köhn= most frequent, high O2 affin
Hb Zurich, normal O2 affin, increased affin for CO
Hb Poole: unstable gamma chain variant
Hb Indianapolis: too unstable to find in blood
g6pd def: caused by?
decreased NADPH; inability ot maintain reduced glutathione
g6pd inheritance?
x-linked…but girls can still have if lyonization
smear findings in G6PD?
heinz bodies, blister cells
WHY should you wait until crisis over until testing for G6PD def?
retics have 5x higher g6pd…wait 1-2 months after
classes of g6pd?
1-4 (roman numerals)
1: <10% normal, chornic
2: <10% normal, episodic severe, mediterranean
3: 10-60%…G6PD A-= 15% of African Americans
4: >60%…so symptoms
give 10 oxidative triggers in G6pd
dapsone methylene blue fava beans henna rasburicase napthalene glyburide nitrofurantoin primaquine TNT=trinitrotoluene
PK def: associated with increased or decreased 2,3 DPG?
increased
PK def–> what within the RBC
less ATP–> loss of membrane stability, hemolysis
PK def inheritance?
AR
PK def gene?
PKLR
dx PK def how?
enzyme activity AND sequencing of PKLR
in pk def: if undergo splenomegaly, what happens?
reticulocytosis!!! retics may increased from 10-15–> 30-70%
other than g6pd def and pk def, give two other enzympatothies
glucose phophsate isomerase def
pyriidine 5’ nucleotidase def
normal heme group is Fe what?
2+= ferrous….when gets oxidized–> 3+ = ferric–> more oxygen affinity–> decreased O2 delivery
drug that can –> methemoglobinemia?
lidocaine
AD blue baby with brown blood..dx?
Hb M variant; methemoglobinemia
what type of methemoglobinemia is AR?
NADH MetHb reductase def
tx for methemoglobinemia?
remove inciting agent
give O2
methylene blue to increased reduction of met hgb..can’t give if g6pd def though
at what level of methb does pt become cyanotic?
10-15%
DAT= direct coombs…how does this work?
take pt blood sample; add anti-human IgG= coombs reagent–> agglutinate if there were ALREADY antibodies prsent on the pt’s cells that the coombs reagent is responding to as secondary abs
3 subtypes of immune mediated hemolysis?
- autoimmune HA
- paroxysmal cold hemoglobinuria
- cold agglutinin disease
AIHA: ab type?
IgG +/-C3
PCH: Ab type?
IgG= Donath Landsteiner Ab…DAT often neg becuase sample needs to go to lab warm! and lab has to check for it!
Cold agglutinin disease Ab type?
IgM= DAT C3+
temp for AIHA?
37C
antigen in AIHA?
common or panractive…will have direct adn indirect coombs + because reacts to lots of things
AIHA: intra or extravasc?
extra
causes of AIHA?
idiopathic rhuem immunodef evans infections malig
tx for AIHA?
transfusions long course of steorids=1st ritux=2nd splenectomy' immunosupp
AIHA prog?
often recurs
pCH temp?
Ab binds at 4C, fixes C3 as warms to 37C
antigen in PCH?
P
PCH: intra or extravasc?
intra
cause of PCH?
viral infection
PCH tx? 2
Blood/IVF warmer
supportive
cold agglutinin disease: temp?
4C
Antigen in cold agglutinin disease?
I/i
cold agglutinin diseaes site of clearance?
intravasc
causes of cold agglutinin disease? (2)
mycoplasma, EBV
tx of cold agglutinin disease?
blood/IVF warmer
supportive
plasmapheresis if severe (because IgM!!)
prog in PCH?
self-limited
prog in cold agglutinin diseaes?
self-limited
hemolytic diseae of newborn: egs?
Rh incompat
ABO incopat
minor incompat
tx hemolytic disease of newborn how?
exchange transfusion, phototherpya, RBC transfusions
Rh hemolytic disease: lab findigns? 3
baby’s DAT positive
mom’s indirect coombs will be positive because she’ll have ab to paternal antigen
infant smear: nRBCs, polychromasia
ABO incompatib: typically IgM or IgG?
IgM, but only IgG can cross placenta
Can ABO incompat happen in first preg?
yes
what is ABO incomp usually not severe?
ABO antigens not expressed in early fetal RBCs
see what on baby’s smear if ABO incompat?
polychromasia
nRBCs
spherocytes
MAHA= miroangiopathic HA: see hwat on smear?
schistocytes
MAHA: 5 egs?
DIC TTP HUS Kasabach-Merrit burns BMT (allo>auto) cyclosproine tacro
marcoangiopathic HA: see what on smear?
shcistocytes
macroangiopathic hemolysis (larger vessels): causes?
- congen heart disease, esp after surgery wtih rough suture line or reisdual high pressure gradient jet
- march hemolysis
TTP: caused by?
def or Abs to ADAMTS13
lack of ADAMTS13 –>?
ultralarge VWF multimers–> fibrin dep, plt trapping, microangipathiy
name of congen ADAMTS13?
Upshaw-Schulman syndrome
causes of secondary ADAMTS13? 4
rheum, preg, infections, idiopathic
TTP pentad?
MAHA, thrombocytopenia, renal dysfunction, neuro changes, fever
how to dx TTP?
-intravasc hemolysis, low plts, normal PT/PTT/ibrinogen, schistocytes on smear..low ADAMTS13 activity and positive abs but slow turnaround
tx for TTP?
urgent plasmapheresis for acuired TTP with steroids and/or other immunosupp (ritux); caplacizumab for adults…dont’ wait for ADAMTS13 results!
HUS or TTP more common?
HUS
HUS traid?
MAHA< low plts, renal dysfucntion
pathophys of classic HUS?
shiga toxin from e coli O157:H7 infection..get bloody diarrhea
pathophys of ATYPICAL HUS?
sporadic = due to infections…or familial = mutations in complememtn control proteins…may not have bloody diarrhea
HUS: ADAMTS13 result?
normal
classic HUS tx?
supportive care
atypical HUS tx?
supportive care, plasma therpay, eculizumab (blcoks C5–> C5a, C5b), renal or liver transplant
Paroxysmal noctrunal hemobloginuria: tx?
eculizumab
drug induced HA eg?
pencillin–> haptenization
toxin associated hemolysis eg?
clostridium sepsis, brown recluse spider bite, wilson’s disease, burns
dx wilsons how?
serum copper, ceruloplasmin levels
Rh null phenotype hemolysis pathophs?
absenet or markeldy low Rh expression (unlike Rh- which refer to D antigen ONLY), due to mutations in RHAG gene
findings in Rh null phenotype?
mild-mod hemolytic anemia
increased osm frag
elevated HbF
smear: stomatocytes
management issue in Rh null phenotype?
may form ab to Rh antigens when transfused RBCs
