Normocytic Anemia - Predominalty Intravascular Hemolysis Flashcards
Explain the problem with paroxysmal nocturnal hemoglobinuria? Everything, cause, effect.
RBCs are always around complement system so they must be protected by it. RBCs have DAF and MIRL molecules on their surfaces to inactivate complement if it comes close. These two molecules are held on to the surface by a linking molcule called GPI. The problem with this disease is you have an acquired mutation in the myeloid cell resulting in no GPI, which means no DAF or MIRL. When we sleep, we have a mild respiratory acidosis because we breath more shallow which builds CO2 up. So during the night RBCs, WBCs, and Platelets get lysed. Remember, acidosis activates complement.
What 3 lab values do we see with PNH?
Hemoglobin in the blood, hemoglobin in the urine, and hemosiderin in the urine
What test is used to screen for the test and what two tests confirm it?
Sucrose test screens it
Acidity the serum and check for lack of CD55 or DAF confirms
What are two complications in these folks and why? What is the most common cause of death in these folks?
Iron deficiency anemia because of the loss of hemoglobin in the urine. AML because if there is one mutation there can be another one.
Cause of death is thrombosis in the portal vein, cerebral vascular and hepatic vein because platelets are being lysed as well.
What is the problem with G6PD deficiency? Cause, effect, everything?
X linked recessive disorder resulting in the reduction of the half life of G6PD. RBCs are always in environments of oxidative stress, for example H2O2. RBCs have glutathione that can reduce H2O2, but becomes oxidized at the same time. Needs to be regenerated by NADPH constantly. NADPH is produced by G6PD. So, the problem is, no G6PD, no NADPH and you are not regenerating glutathione. Leads to oxidative injury and intravascular hemolysis.
What are the two variants of G6PD deficiency?
African variant where there is a mild reduction in half life so mild hemolysis
Mediterranean variant where there is a more severe reduction in half life and more marked hemolysis
What are 3 causes of oxidative stress, what does the oxidative stress do to hemoglobin in the RBC, what do macrophages do to it?
Infections, drugs, and favs beans
Precipitates the HbG into a Heinz body.
Macrophages take bites out of the RBC to get the precipitate leading to bite cells.
2 clinical signs of G6PG deficiency?
Hemoglobin and back pain
How do we screen for the disease and when is it best to do?
Heinz preparation but do it after the acute hemolytic flare up
Explain simply, not the whole deal, what immune hemolytic anemia is?
Antibody mediated destruction of RBCs, either IgG or IgM
What’s going on if it is IgG?
IgG binds the RBCs in the warm central part of body, heads to the spleen and is eaten up by splenic macros and cause spherocytosis.
Causes extravascular hemolysis
Immune hemolytic anemia is associated with what 3 conditions and which one is most common?
Lupus (most common), CLL, and certain drugs like penicillin and cepahlorsporin.
What two ways does the drug cause immune hemolytic anemia?
The drug may bind to the RBC and then the antibiotic.
Or the drug produces autoantibodies, like methyldopa, and then those goes after the RBC.
4 ways to treat IgG immune hemolytic anemia?
Stop drug, steroids, IVIG, and take out the spleen if it gets bad
How does IgM hemolytic anemia work?
Fixes complement on the RBC in the colder areas of the body, extremities, and the splenic macrophages identify C3b and start eating them making spherocytosis.
