Hemolytic Anemias Flashcards
three ways to become anemic
- lost too many red cells
- not make enough red cells
- both
reasons for red cell loss
- hemorrhage (obvious or occult)
2. hemolysis
measurements for hemolysis
*looking in serum/urine for anything inside a RBC
- unconjugated billirubin (inc)
- haptoglobin (dec) and acute phase reactant
- hemoglobinuria
- LDH (non specific)
- visible hemolysis
Peripheral blood smear in hemolysis with healthy bone marrow=
polychromasia, nRBC’s, increased reticulocytes
genetic targets: weakness in MEMBRANE proteins
BAND 3, SPECTRIN,ANKYRIN ETC
herediatry syndromes with genetic defects in membrane proteins
hered. spherocytosis, eliptocytosis, pyropoikilosis, stomatocytosis
dx. of genetic membrane defect
osmotic fragility test
genetic target: hemoglobin–>
Hemoglobinopathies–>MISSENSE MUTATIONS
HGB S, C, SC, E, OTHERS
DX OF HEMOGLOBINOPATHIES
HEMOGLOBIN ELECTROPHORESIS
DISEASE ASSOCIATED WITH HEMOGLOBINOPATHIES
hemoglobin crystals–> hemoglobin c disease
–>causes precipitation of Hgb
genetic defect in atp generating system (glycolysis)->
pyruvate kinase def–> cant make atp from glucose, no E to maintain N/K pump–>osmotic gradient lost–>cell ruptures
Pyruvate kinase deficiency results in
polychromasia
–>increased reticulocytes, nRBC’s,
dx of pyruvate kinase def.
enzyme activity test
Genetic defect involving anti-oxidant system
- g6PD deficiency
2.
one of the most common genetic defects
G6PD
inducers of G6PD
fava beans
desperone
primaquin
Bactrim
Who gets G6PD def
X linkes-MALES in malaria endemic areas
dx of G6Pd
enzyme activity test
BLISTER CELL
G6PD deficiency
oxidative damage to Hgb causes
disulfide linkages between Hgb molecules–> heinz bodies and blister cells
One of the first enzymes in glucose phosphate shunt
G6PD
How does the cell handle ROS–>
reduced by GSH
how is GSH replenished
NADPH produced by alternative to glycolysis–>pentose phosphate shunt
heinz bodies
oxidized Hgb–>that has coalesced to form aggregates via disulfide bonds
extensive oxidation of heme iron
methemoglobinemia
how is methemoglobin returned to hemoglobin
cytochrome b5 reductase (methemoglobin reductase)
co-factor required for methemoglobin reductase
NADH–>made during glycolysis
neoplastic/acquired defect in surface poteins that inhibit MAC complex
PNH–>acquired, clonal, NON MALIGNANT, mutation
dx of PNH
flow cytometry
spherocytes…
hereditary sperhocytosis
genetic basis for PNH
mutation in PIG-A gene which makes a GPI anchor for DAF–>cannot prevent random mac formation on RBC–>hemolysis
is PNH inherited
no–>it is acquired and clonal in the Bone Marrow-> that specific clone just over takes the normal blast lines
tx for PNH
- allogeneic BMT
2. ecluzimab (200K/year
PIGa is on what chromosome
X linked
how do the red cells look in PNH
normal
presentation of Malaria
travel to endemic areas, dark urine, fever, jaundice
*hemolysis
forms of malarial parasite in rbc
early merozoites
late gametocytes
more lethal malaria
falciparium (anopheles)
babesia
tick, MA, RI, NY–>hemolysis
causes peruvian warts
bartonella bacilliformis
*hemolytic anemia and splenomegaly
vector for bartonell abacilliformes
sand flies
endemic area for oroyo fever
peru, columbia ecuador
c. perferenges
normal skin floar that can cuase hemolysis (via a secreted alpha toxin) if exposed in septic abortions or trauma
*rarely a comlication of cholesytitis
can cause gas gangrene
C. perferenges
Warm AHA occurs via which isotype
IgG
Warm AHA will be positive at what temp
37 degrees
What will Warm AHA be positive for at 37 degrees
compliment and antibodies
AHA antibodies are cleared by
RES macrophages
(reticuloendothelial)
SPLEEN AND LIVER
how do RES function to remove AHA
just take a bite out of plasma membrane and remove the AHA antibody–> leave as much Hgb in tact as possible
*ratio of membrane to cell volume is reduced–>no longer biconcave disks
Outcomes of Warm hemolytic anemia
1/ clearance via phagocytosis
2/partial clearance–> microspherocytes
3/COMPLIMENT (c1 and c3B) fixation and MAC hemolysis
*macrophages can recognize compliment as well as antibodies
Clues to dx for Warm AHA
1/ hemolysis by serum testing 2/ polychromasia 3/ basophillic stipling 4/ microspherocytosis 5/ nRBC's 6/ NO blasts or myelocytes
test for Warm AHA
DAT–> add ab’s for IgG or compliment
*+ for agglutination at 37degrees
Why use IAT for Warm AHA
if red cells wit bound Ab’s are phagocytosed to quickly to detect–>the pt’s serum should still be reactive–>use exogenous RBC’s and pt.’s serum–> throw in coombs reagent–> + agglutination
COLD AHA mediated by what isotype
pentameric IgM at room temperature or below
Positive at 37 degrees for C3
define cold AHA…
*cold agglutinins
typically found only in the periphery
autoreactive at low temperature–>upon return to core body temp they are released
*all you will see at 37 is positive for compliment–> ab’s will have already dislodged
worst case scenario that COLD aha can cause
raynaud’s
hemolysis–>can fix cimpliment
C1-C3b–>MAC
clues to Dx of cold hemolytic anemia
>Raynaud's >hemolysis by serum testing >RED CELL AGGLUTINATION >polychromasia >basophillic stippling >nRBC's >no blasts or myelocytes
LAB error in cold aha
HCT will be artifactually low due to RBC agglutination
Warm AHA associated with which other conditions
Lymphoma
other malignancies
Other autoimmune conditions–>SLE and RA
*prognosis poor
COLD aha associated with which other conditions
Viral syndromes
Mycoplasma penumonia
SLE and RA
Prognosis: chronic, season
tx of warm and cold aha’s
steroids
if that dont work splenectomy
characteristic cell of TTP
shistocytes
Cause of TTP
ADAMTS13 is defective and cannot cleave VWF, VWF that is too long causes too much platelet aggregation and as the RBC’s pass thru the microthrombi they are cleaved into shistocytes and are consumed–>microangiopathic hemolytic anemia
tx of ttp
plasmaphoresis
clinical context of TTP
> female>male
–>FEVER,
RENAL FAILURE, FLUCTUATING CNS SYMPTOMS
DELAYED HEMOLYTIC TRANSFUSION EVENT–
RESPONSE TO A MINOR ANTIGEN THAT TAKES1-2 WEEKS USUALLY–>THERE ARE ABOUT 350 OF THESE MINOR ANTIGENS
JAUNDICE
EXAMPLES JKA AND JKB
