Normocytic Anemia - Intravascular Hemolysis Flashcards
What molecules protect RBCs from complement?
- DAF - Decay accelerating factor
- MIRL
Both anchored to RBC via GpI
What causes Paroxysmal nocturnal hemoglobinuria?
Acquired defect in myeloid stem cells
- GpI is not produced - meaning DAF and MIRL are not able to attach
- Renders cells vulnerable to complement
Why does PNH occur at night?
- Mild respiratory acidosis develops with shallow breathing during sleep and activates complement
What cells are lysed in PNH?
RBCs WBCs and platelets are lysed
What tests are used to diagnose PNH?
- Sucrose test (as screening)
- Confirmatory test is acidified serum test or flow cytometry to detect lack of CD55 (DAF)
What do patients with PNH die from?
- Thrombosis (in hepatic, portal or cerebral veins)
- Destroyed platelets release cytoplasmic contents into circulation inducing thrombosis
What is a complication of PNH?
- Iron deficiency anemia (losing hemoglobin/iron in urine)
- AML (10% of patients)
How is G6PD deficiency inherited?
X-linked recessive
What are G6PD deficienct patients RBCs vulnerable to?
Oxidative stress
What happens to G6P in G6DP deficiency?
Reduced half-life
What is the difference between the African and Meditereanean variant of G6PD deficiency?
- Med - Markedly reduced half-life (cells die are killed more quickly)
- African - Mildly reduced
How long is the half-life of G6PD in normal people
same as RBCs
What (drugs) can cause oxidative stress?
- Primaquine
- Sulfa drugs
- Dapsone
- Fava beans
Also infections
What does oxidative stress result in?
Heinz bodies
What are Heinz bodies removed by?
Splenic macrophages - resulting in Bite cells
What kind of hemolysis is G6PD deficiency predominantley?
Intravascular
What does G6PD deficiency present with?
- Hemoglobinuria + back pain (hours after exposure to oxidative stress)
- Trigger for oxidative stress needed
How is G6PD deficiency screened?
Heinz preparation
- Enzyme studies confirm deficiency (can only do after acute hemolytic episode)
What is immune hemolytic anemia?
Antibody-mediated (IgG or IgM) destruction of RBCs
IgG-mediated immune hemolytic anemia usually involves what kind of hemolysis?
Extravascular hemolysis
IgG-mediated immune hemolytic anemia has what type of cells?
Spherocytes
- Due to membrane of antibody-coated RBCs being consumed by splenic macrophages
What other conditions are associated with IgG-mediated immune hemolytic anemia?
SLE CLL
- Also certain drugs (e.g penicillin or methodopa)
How can IgG-mediated immune hemolytic anemia be treated?
- Cessation of the offending drug
- Steroids
- IVIG - eats these instead of RBCs
- Splenectomy
What kind of hemolysis is involved in IgM-mediated immune hemolytic anemia?
Intravascular
What temperatures are associated with IgM and then IgG mediated immune hemolytic anemias?
- Cold in IgM - cold agglutination
- Warm in IgG
What does the direct coombs test confirm?
Presence of antibody-coated RBCs
- Anti-IgG added to the patients RBCs
- Agglutination occurs if RBCs are already coated with IgG antibody
- Most important test for IHA
What does nthe indirect coombs test confirm?
Anti-IgG antibodis in serum
- Agglutination occurs if serum antibodies are present
Microangiopathic hemolytic anemia has what type of cells?
Schistocytes
What are the different kinds of microangiopathic hemolytic anemias?
- TTP (platelet thrombi - do not have ADAMS13)
What can cause schistocytes?
- Microthrombi (e.g TTP-HUS, DIC, HELLP)
- Prosthetic heart valves
- Aortic stenosis
What can Malaria cause?
A normocytic hemolytic anemia
- Cyclical fever
- Mostly intravascualr but spleen also destroys some infected cells -> splenomegaly
What organism causes Malaria?
Plasmodium falciparum - daily fever
Plasmodium vivax and ovale - fever every other day
What mosquito carries plasmodium?
Anopheles mosquito (female)
What anemias may cause a low corrected reticulocyte count?
- Microcytic and macrocytic
- Renal failure
- Damage to bone marrow precursor cells
What does parvovirus B19 infection result in?
- Infects progenitor red cells
- Temporarily halts erythropoeisis
- Leads to significant anemia in the setting of preexisting marrow stress
- Treatment is supportive
What is aplastic anemia?
- Damage to hematopoietic stem cell
- Results in pancytopenia w low reticulocyte count
What can cause aplastic anemia?
- Drugs/chemicals
- Viral infections
- Autoimmune damage
What would biopsy show in aplastic anemia?
Empty bone marrow - surrounded by fat
How may aplastic anemia be treated?
- Cessation of causitive drug
- Transfusions
- Marrow stimulating factors (EPO, GM-CSF, G-CSF)
- Immunosuppression
- BMT (bone marrow transplant) (last resort)
What is myelophthisic process?
- Pathologic process that replaces bone marrow
- Hematopoiesis is impaired resulting in pancytopenia
