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
- 2-3mg/dl
- 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
- MCH/MCV
- 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?
- Ecchinocyte
- 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?
-
infections
sulfa drugs
naphthalene
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
alcoholism
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
splenectomy - 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
- PCH
- 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
PCH
Cold 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?
-
steroids
splenectomy - What is the treatment for Paroxysmal Cold Hemoglobinuria (PCH)?
-
avoid cold
steroids - What is the treatment for cold AIHA?
-
avoid cold
plasmapheresis. - What are the lab findings in AIHA?
-
anemia
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)
methemoglobin
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
cardiomyopathy -
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
thalassemia
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)