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Toronto Notes 2019 Macrocytic Anemia Hereditary Elliptocytosis
Definition/Etiology
• abnormalityinspectrininteractionwithothermembraneproteins • autosomaldominant
• 25-75%elliptocytes
• hemolysisisusuallymild
Treatment
• immunizations;splenectomyforseverehemolysis
Glucose-6-Phosphate Dehydrogenase Deficiency
Definition
• deficiencyinglucose-6-phosphatedehydrogenase(G6PD),correspondingtoalackofreduced glutathione (GSH) and leading to RBC sensitivity due to oxidative stress
Pathophysiology
• X-linkedrecessive,prevalentinindividualsofAfrican,Asian,andMediterraneandescent
Clinical Features
• frequentlypresentsasepisodichemolysisprecipitatedby: ■ oxidative stress
■ drugs (e.g. sulfonamide, antimalarials, nitrofurantoin) ■ infection
■ food (fava beans)
• inneonates:canpresentasprolonged,pathologicneonataljaundice
Investigations
• neonatal screening
• G6PDassay(maynotbeusefulifresultisnormal)
■ should not be done in acute crisis when reticulocyte count is high (reticulocytes have high G6PD levels)
• bloodfilm
■ Heinz bodies (granules in RBCs due to oxidized Hb); passage through spleen results in the
generation of bite cells
■ may have features of intravascular hemolysis (e.g. RBC fragments)
Treatment
• folicacid
• stopoffendingdrugsandavoidtriggers • transfusioninseverecases
Macrocytic Anemia
• MCV>100fL
• seeFigure2,ApproachtoAnemia,H6
Table 15. Comparison Between Megaloblastic and Non-Megaloblastic Macrocytic Anemia
IgG
Fc portion of IgG
Hematology H23
RBC Macrophage
Fc Receptor
Spherocyte
Figure 10. Spherocytosis secondary to AIHA
Glucose
􏰁O2 H2O
􏰀 2GSH GSSG
NADP+ NADPH􏰀
G6P G6P
Lactate
G6PD
6PG
6PGD Pentose Phosphate
Morphology Pathophysiology
Megaloblastic
Large, oval, nucleated RBC precursor Hypersegmented neutrophils
Failure of DNA synthesis resulting in asynchronous maturation of RBC nucleus and cytoplasm
Non-Megaloblastic
Large round RBC Normal neutrophils
Reflects membrane abnormality with abnormal cholesterol metabolism
Figure11.G6PDdeficiency
Causes of Macrocytic Anemia ABCDEF
Alcoholism (liver disease)
B12 deficiency
Compensatory reticulocytosis Drugs (cytotoxic, AZT)/Dysplasia Endocrine (hypothyroidism)
Folate deficiency/Fetus (pregnancy)
Characteristics of Megaloblastic Macrocytic Anemia
• Pancytopenia
• Hypersegmented neutrophils
• Megaloblastic bone marrow
© Kristina Neuman 2010