SM 213a - Thromboembolic Microangiopathies Flashcards
What causes TTP?
TTP = thrombotic thrombocytopenic purpura
Caused by deficiency in ADAMTS13 due to genetic mutation or autoantibodies. Requires a trigger to cause TTP
- Without ADAMTS13, you cannot chop up large multipers of Von Wilebrand factor
- This leads to uncontrolled platelet aggregation and thrombus formation
Decreased activity of which protein could cause endotheliosis (capillaries to fill with endothelial cells)
Decreased activity of VEGF -> Endotheliosis. This can lead to TMA
VEGF stimulates angiogenesis
Genetic susceptibility + anti-VEGF drugs or pregnancy
-> Decreased VEGF activity
What is the most prominent stimulator of endothelial cell production and podocyte growth?
VEGF
VEGF receptors are highly expressed in the glomerular endothelium
May be inhibited by pregnancy or drugs
How does preeclampsia develop?
Abnormal placenta: Abnormal spiral artery remodeling
- -> Hypoxia
- -> Increased sFlt1 (a VEGF receptor decoy)
- -> sFlt1 binds VEGF, decreasing the effective VEGF concentration in the bloodstream
- -> Decreased VEGF activity
- -> Loss of ENOS -> HTN
- -> Damage to glomerular endothelium or other vascular bed -> Thrombus formation (TMA)
Which TMA is associated with mutations in complement regulatory proteins?
Atypical HUS
What is the pentad associated with TTP?
- Hemolytic andemia
- Thrombocytopenia
- Neurologic symptoms
- Kidney injury
- Fever
What is the initial event in all forms of TMA?
Damage to the vascular endothelium
- > Thrombus formation
- > Shear stress in the microvascular with thrombi (-> Shistocytes)
- > Thrombocytopenia
Glomerular microvascular is particularly susceptible to injury
What is the triad that characterizes thrombotic microangiopathies (TMAs)?
- Microangiopathic hemolytic anemia
- Thrombocytopenia
- Organ injury (Due to small clots that form in microvasculature)
