Thrombotic Microangiopathies Flashcards
What are the 3 shared features of all thrombotic microangiopathies (TMAs)?
- microangiopathic hemolytic anemia
- thrombocytopenia
- organ injury due to microthrombi
Define “renal restricted” thrombotic microangiopathy
when the only organ that is affected by microthrombi is the kidney
What is the first event in all forms of TMA?
Damage to the vascular endothelium is the initial event in all forms of TMA.
Why does hemolytic anemia occur in TMA?
Fragmented red blood cells (hemolytic anemia) occurs due to shear stress in microvasculature with thrombi.
Why does thrombocytopenia occur in TMA?
Thrombocytopenia occurs due to platelet consumption in thrombi.
Why is the glomerulus so susceptible to injury in TMAs? (4)
- fenestration
- high capillary pressure
- exposure to toxins and complement activation of high blood flow
- GBM is very pro thrombotic, and can be exposed when the endothelium dies
What are the 3 factors that can protect the glomerular microvascular bed in TMAs?
- VEGF
- complement regulatory proteins
- ADMTS13 - a VWF protease that limits platelet aggregation
What is ADAMTS13?
a VWF protease that breaks down VWF multimers to prevent platelet aggregation and therefore, thrombi. it is very low in some forms of TMA
What are the 3 main classes of TMA?
- thrombotic thrombocytopenic purpura
- hemolytic uremic syndrome
- “other”
What are the 2 main subtypes of hemolytic uremic syndrome, which is a TMA
- typical/diarrheal (D+HUS)
2. atypical complement mediated
What causes typical HUS?
shiga toxins, which cause diarrhea in E Coli infections as well as HUS
What causes atypical HUS?
abnormalities in complement regulation, without shiga toxin
What are the 2 main types of “other” TMAs?
anti-VEGF
endothelial damage due to other causes
Preeclampsia and HEELP syndrome are examples of what kind of TMA?
anti VEGF associated
Drugs such as bevaciumab, sutent and sorafenib can cause what kind of TMA?
anti-VEGF associated TMA
transplant rejection, HIV, cancer, drugs, connective tissue disease, malignant hypertension, antiphospholipid syndrome can all cause what kind of TMA?
endothelial damage associated TMA
What is the presentation of thrombotic thrombocytopenic purpura? (5)
hemolytic anemia, thrombocytopenia, neurologic symptoms, kidney injury, fever
hemolytic anemia, thrombocytopenia, neurologic symptoms, kidney injury, fever
This is a typical presentation for what disease?
thrombotic thrombocytopenia purpura
What causes TTP?
-absence of ADAMTS13 activity (due to genetic mutation in ADAMTS13 gene OR autoantibodies to ADAMTS13) leads to large multimers of von Willebrand Factor (VWF) that increase platelet aggregation and thrombus formation
How is TTP treated?
plasmapheresis and exchange (remove the antibody and/or give back the enzyme)
What strain of E coli causes HUS?
O157
Who is most commonly affected by D+HUS?
children, due to E Coli infection
What pathophysiology is responsible for D+HUS?
Gb3 receptor on glomerular endothelial cells causes platelet thrombi when shiga toxin binds
When is D+HUS treated with drugs?
with severe neurological involvement
