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Pediatric Hematology: Congenital and Acquired Hemolytic Anemias


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Do RBCs contain more AST or ALT?
AST (2-3:1)
How high does bilirubin have to be to see sceral icterus
Clinical picture of congenital spherocytosis
hemolytic anemia, (early) gallstones, splenomegaly, jaundice
Inheritance pattern of congenital spherocytosis
2/3 autosomal dominant
1/3 spontaneous mutation
how do you calculate MCHC
What scenerios make interpretation of osmotic fragility test difficult?
s/p transfusion (not patient's own cells)
high reticulocyte count
young age - less than 6-12 months
What is the difference between the African and the Asian variants of hereditary elliptocytosis?
African has mild hemolysis, Asian is more severe hemolysis.
Name two X-linked inheritence RBC enzyme disorders
G6PD Deficiency
Phosphoglycerate kinase (PGK) deficiency
What morphological finding is associated with pyruvate kinase deficiency?
Pathophysiology of pyruvate kinase deficiency?
decreased synthesis of ATP -> high 2,3DPG levels -> greater O2 release at low hemoglobin concentrations
How does the type of hemolysis differ between pyruvate kinase deficiency and G6PD deficiency?
Pyruvate kinase: extravasular
G6PD: intravascular
What can initiate a hemolytic reaction in a patient with G6PD?
sulfa drugs
antimalarial drugs
When should you test for G6PD?
After the resolution of a acute event.
What morphologic finding is associated with pyrimidine 5'-nucleotidase deficiency?
basophilic stippling
What is basophilic stippling?
precipitated (condensed) ribosomal protein (RNA)
When is basophilic stippling seen?
lead poisoning
severe bacterial infection
drug exposure
anemias with impaired hemoglobin synthesis
megaloblastic anemia
refractory anemia.
What is a Heinz body?
a cellular inclusion in a RBC that consists of damaged (unstable/denatured) aggregated hemoglobin,
associated with some forms of hemolytic anemia
What infection are patients with congenital hemolytic anemia at greater risk for?
Parvo B19 infection
Interventions for patients with congenital hemolytic anemia
Folate supplementation
RBC transfusions
What are the two types of inherited hemolytic disorders
RBC membrane disorder
RBC enzyme disorder
What is the mode of inheritance for RBC membrane disorders? for enzyme disorders?
membrane: AD
enzyme: AR
What are the results of osmotic fragility tests in RBC membrane disorders? in RBC enzyme disorders?
membrane: abnormal
enzyme: normal
what are the results of autohemolysis test with RBC membrane disorder? with RBC enzyme disorder?
membrane: corrects with glucose
enzyme: no correction
What is the response to splenectomy in RBC membrane disease? in RBC enzyme disease?
membrane: complete response
enzyme: parital response
What are the three types of hemolytic anemia caused by erythrocyte autoantibodies?
Warm Reactive IgG antibodies
Cold Reactive IgG antibodies (Paroxysmal Cold Hemoglobinuria)
Cold agglutinin disease
What type of antibody mediates:
- Warm AIHA
- Cold agglutinin disease
Warm: IgG +/- complement
PCH: IgG + complement
Cold: IgM + complement
What are warm and cold antibodies?
Warm antibodies are immunoglobulins that bind to erythrocyte membrane antigens at 37 degrees, they rarely fix complement. They are ususally IgG.
Cold antibodies optimally bind to erythrocyte membrane antigens at 4 degrees, they usually fix complement and they are usually IgM.
What is the Donath-Landsteiner antibody?
An IgG autoantibody that is responsible for hemolysis seen in paroxysmal cold hemoglobinuria. Unlike most IgG it binds antigen at 4 degrees and it can fix complement.
What does DAT stand for?
Direct Antiglobulin test
What can DAT detect?
IgG or C3 bound to the RBC surface (using monoclonal antibodies against IgG or C3)
Why test for C3 and not IgM?
IgM isotypes typically efficiently bind complement
IgM antibodies tend to spontaneously dissociate from the RBC membrane and therefore might not be reliable
Is the hemolysis associated with AIHA intravascular or extravascular?
Warm: ususally extravascular (IgG does not fix complement, instead it coats the RBC which is then destroyed in the spleen)
Cold: usually intravascular (b/c the IgM fixes complement)
What is the antigen specificity for:
warm AIHA
warm: Rh and others (anti-U, anti-Kell, anti-Jka, Anti Fya)
PCH: P antigen
Cold: I,i
What is the treatment for warm AIHA?
What is the treatment for Paroxysmal Cold Hemoglobinuria (PCH)?
avoid cold
What is the treatment for cold AIHA?
avoid cold
What are the lab findings in AIHA?
elevated LDH
elevated indirect bilirubin
low haptoglobin
Do you see dark urine in warm or cold autoimmune hemolytic anemia?
Cold b/c it is an intravascular hemolysis
What are the most common CNSHA (Congenital non-spherocytic hemolytic anemias)
G6PD deficiency
Pyruvate kinase deficiency
What varient of G6PD deficiency is found in the mediteranean population? african?
mediterranean: B- (more severe)
African: A-
pathophysiology of PNH (paroxysmal Nocturnal hemoglobinuria)
defect in the formation of RBC surface protein anchor: GP1. Therefore surface proteins: CD 55, CD 59 are not able to be sufficiently anchored. B/c of this there is increased complement mediated cell death. -> anemia
How do you test for PNH?
Flow cytometry: absent or reduced CD 55 and CD 59 (b/c they cannot anchor to the RBC surface)
When do you see Heinz bodies? What else would be abnormal on electropheresis?
In the presense of unstable denatured hemoglobins. You would see other hemoglobins beside Hgb A.
what causes the oxygen dissociation curve to shift to the left (decreased tissue delivery)
fetal hemoglobin (binds less 2,3DPG)
alkalosis (increased pH)
low temp
what is triose phosphate isomerase characterized by
AD inheritance
hemolytic anemia
neonatal hyperbilirubinemia
progressive neurologic dysfunction
increased susceptibility to infection
Match the disorders with the associated pathways

triose phosphate isomerase deficiency
pyruvate kinase deficicency
G6PD deficiency

glycolytic pathway
hexose monophosphate shunt
Embden Myerhof pathway
triose phosphate isomerase deficiency - Embden Myerhof pathway

pyruvate kinase deficiency - glycolytic pathwasy

G6PD deficiency - hexose monophosphate shunt
in what conditions are Heinz bodies seen
unstable hemoglobin (including HgB Koln, Zurich, Gamma)
G6PD deficiency
Hemoglobin H
what are pappenheimer bodies
degenerating cellular remnants which contian iron and are most likely related to accelerated red cell division or impaired hemoglobin synthesis
when are pappenheimer bodies seen
severe anemia
s/p splenectomy
what MCHC would be very suggestive of spherocytosis
MCHC > 36%
what is the most common ABO set-up for hemolytic disease of the newborn
O mom
A baby
why is plasmapheresis helpful in the treatment of TTP
TTP is due to absence of vWF cleaving protease - either congenital or acquired (inhibitor)
plasmapheresis removes the inhibitor and replaces the missing protease (in FFP)

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