5.6 and 5.7 Intravascular hemolysis and underproduction Flashcards
What are the two components on RBCs that inhibit complement activation?
MIRL
DAF (CD55)
What is the function of DAF?
Accelerates the decay of C3 convertase
What is the anchoring protein found on RBCs that allow for DAF and MIRL to stick?
GpI
What is the cause of PNH?
Acquired defect in myeloid stem cells, that deletes the GpI anchor on RBCs, allowing RBCs to be destroyed by complement
What accounts for the paroxysmal part of PNH?
Shallow breathing at night causes a mild respiratory acidosis, leading to the activation of complement
What type of hemolysis occurs with PNH? What, then, are the common s/sx?
Intravascular:
- Hemoglobinemia
- Hemoglobinuria
- Hemosiderinuria
What is the screening test for PNH, and how does it work?
Introduce sucrose into the serum, which activates complement
What is the confirmatory test for PNH?
Acidified serum test or flow cytometry for a lack of CD55
What is the main cause of death in patients with PNH? How does this occur?
Thrombosis (e.g. of hepatic, portal, or cerebral veins)
-Destroyed platelets release cytoplasmic contents into circulation, inducing thrombosis
What causes the Fe deficiency anemia that occurs with PNH?
Loss of Fe in urine
What is the cancer that occurs with PNH?
AML due to mutation in myeloid stem cell
What is the inheritance pattern with G6PD deficiency?
XLR
What is the molecule that reduces the H2O2 and other free radicals in RBCs?
Glutathione
What is the pathophysiology behind G6PD deficiency?
Reduced half life of G6PD prevent the reduction of NADP to NADPH, meaning that glutathione cannot be reduced to prevent RBCs from being damaged from oxidative stress
What are the two variants of G6PD deficiency?
- African = mildly reduced half life of G6PD
- Mediterranean = markedly reduced half life of G6PD
What is the thinking behind the preponderance of G6PD deficiency?
Protective effect against falciparum malaria
What are the causes of oxidative stress that classically precipitate G6PD episodes?
- Fava beans
- Sulfa drugs
- Primaquine
- Dapsone
What is the classic PBS finding in G6PD deficiency? Why?
Bite cells from removal of Heinz bodies
What type of hemolysis occurs with G6PD deficiency?
Intravascular
What happens to Hb when it is exposed to oxidative stress?
Precipitates as a Heinz body
What are the classic s/sx of G6PD deficiency?
Hemoglobinuria and back pain hours after exposure to an oxidative stress
What is the screening and confirmatory test for G6PD deficiency?
- Screen = Heinz prep
- Confirmatory = enzyme studies
What are the antibody classes that cause immune hemolytic anemia?
IgG or IgM
IgG mediated immune hemolytic anemia usually results in intra or extravascular hemolysis? Why?
Extravascular, since
Why should you never perform an enzyme test for immune hemolytic anemia during an acute attack?
Cells that lack the enzyme will be destroyed, and thus will result in a false negative test
IgG binds to RBCs centrally or peripherally in immune hemolytic anemia? IgM?
IgG = centrally IgM = peripherally
What happen to RBCs with immune hemolytic anemia? Why?
Spherocytosis due to a slow loss of membrane
What are the two major diseases in which warm agglutinins occurs?
SLE
CLL
How does PCN lead to immune hemolytic anemia?
Drug attaches to RBC membrane, allowing for IgG to attach to and destroy RBCs
How does methyldopa lead to immune hemolytic anemia?
Drug induces immune antibodies itself
What is the treatment for immune hemolytic anemia? (4)
- Cessation of drug
- Steroid
- IVIG
- Splenectomy
Cold agglutinins (IgM mediated immune hemolytic anemia) is associated with what infectious diseases?
- Mycoplasma pneumoniae
- EBV
What is the diagnostic test for immune hemolytic anemia?
Coombs test
What is the direct coombs test?
Patient’s RBCs added to anti-IgG antibody. Will agglutinate if RBCs are already coated with IgG
What is the indirect coombs test?
Take normal RBCs and add to patient’s serum.
Anti-IgG is then added to test for the presence of ab-RBC complexes
What are the thrombi composed of with TTP?
Platelets
What is the enzyme that is deficient in TTP? What does this cause?
ADAMTS13- prevents vWF polymer from being broken down into monomers, resulting in
What are the thrombi composed of in DIC?
Platelet and fibrin
What is the characteristic PBS finding of microangiopathic anemia?
Schistocytes
What are the heart pathologies that may lead to schistocyte formation?
- Prosthetic heart valves
- Aortic stenosis
What is the characteristic PBS findings of plasmodium falciparum?
Banana
What is the characteristic PBS finding of babesiosis?
Maltese cross
What is the vector for malaria?
Anopheles mosquito
What causes the s/sx of malaria?
Intravascular hemolysis of RBC that occurs as a part of plasmodium life cycle
What is the species of plasmodium that causes daily fevers?
Falciparum
What is the species of plasmodium that causes fevers every other day? What is the treatment?
Vivax and ovale
Praziquantel
What is the diagnostic finding of anemia 2/2 underproduction?
Low corrected reticulocyte count
What are the three major etiologies of anemia 2/2 underproduction?
- Macro or microcytic causes
- Renal failure
- Bone marrow precursor cell damage
What is the treatment for underproduction anemia 2/2 parvovirus B19 infection?
Supportive
What is the cause of aplastic anemia?
Damage to HSC, resulting in a pancytopenia
What is the CD marker for hematopoietic cells?
CD34
What antipsychotic drug classically causes agranulocytosis?
Clozapine
What are the common etiologies of aplastic anemia?
Drugs
Viruses
Autoimmune damage
What is the classic bone marrow aspirate finding of aplastic anemia?
dry tap–fat in bone
What is the treatment for aplastic anemia, besides obviously d/c drugs that cause it? (4)
- Transfusions
- Marrow stimulating factors
- Immunosuppression
- BMT
What is a myelophthisic process?
Pathologic process that replaces bone marrow. This impairs hematopoiesis, and resulting in a pancytopenia
