Normocytic anemias with predominant intravascular hemolysis Flashcards
An acquired defect in myeloid stem cells that results in the absents of glycosylphosphatiylinositol (GPI), allowing cells to be susceptible to destruction by complement…
Paroxysmal Nocturnal Hemoglobinuria (PNH)
What is on the surface of RBCs to protect against complement-mediated damage by the inhibition of C3 convertase?
Decay accelerating factor (DAF)
What is the anchoring glycolipid that secures DAF to the RBC?
GPI
What does the absence of GPI in paroxysmal nocturnal hemoglobinuria (PNH) lead to?
Absence of DAF—leave the cell susceptible to complement-mediated damage
Why is episodic intravascular hemolysis often seen during the night while sleep when patients have paroxysmal nocturnal hemoglobinuria (PNH)?
Respiratory acidosis develops with shallow breathing during sleep which activates complement—lysing RBCs, WBCs, and platelets
Intravascular hemolysis seen with paroxysmal nocturnal hemoglobinuria (PNH) can lead to what clinical findings?
Hemoglobinemia
Hemoglobinuria
Hemosiderinuria days after hemolysis
What screening test is used to test for paroxysmal nocturnal hemoglobinuria (PNH)?
Sucrose test
What confirmatory tests can be used to diagnose paroxysmal nocturnal hemoglobinuria?
Acidified serum test
Flow cytometry—detect lack of CD55 (DAF) on RBCs
What is the main cause of death seen with paroxysmal nocturnal hemoglobinuria?
Thrombosis of the hepatic, portal, or cerebral veins
What are the 2 major complications seen with paroxysmal nocturnal hemoglobinuria (PNH)?
Iron deficiency anemia—due to chronic loss of Hb in urine
Acute myeloid leukemia (AML)
G6PD deficiency allows cells to be susceptible to what?
Oxidative stress
What is the by-product of G6PD needed to regenerate reduced glutathione to prevent oxidative stress to cells?
NADPH
What are the 2 major variants seen with G6PD deficiency?
African variant
Mediterranean variant
What is seen with the African variant of G6PD deficiency?
Mild reduction in the half-life of G6PD causing mild intravascular hemolysis with oxidative stress
What is seen with the Mediterranean variant of G6PD deficiency?
Markedly reduced half-life of G6PD causing major intravascular hemolysis with oxidative stress
Oxidative stress on hemoglobin causes what to form?
Heinz bodies
What are some causes of oxidative stress seen in G6PD deficiency?
Infection
Drugs (Primaquine, sulfa drugs, dapsone)
Fava beans
What type of cells are formed when Heinz bodies are removed from RBCs by splenic macrophages?
Bite cells
Patient presents with hemoglobinuria and back pain hours after the injection of fava beans. What is the most likely underlying cause of this patient’s presentation?
G6Pd deficiency
What screening test is used to screen for G6PD deficiency?
Heinz preparation
An IgG-mediated autoimmune disease that usually involves extravascular hemolysis…
Immune hemolytic anemia (IHA)
What type of cells are formed when IgG binds RBCs and are consumed by splenic macrophages?
Spherocytes
What are the 3 associations that can be seen with immune hemolytic anemia (IHA)?
SLE (most common cause)
CLL
Certain drugs—penicillin and cephalosporins
What drug is known to cause production of autoantibodies that bind self antigens on RBCs?
a-methyldopa
