Thrombotic microangiopathies Flashcards
What are thrombotic microangiopathies?
A group of diseases characterized by widespread microvascular thrombosis.
How do patients present clinically?
- microangiopathic hemolytic anemia
- Thrombocytopenia
- renal failure
What are the possible causes of Thrombotic microangiopathies?
- HUS (primarily in children
2. TTP (primarily in adults)
What is the etiology of Thrombotic microangiopathies?
Typically there are fibrin thrombi in the microvasculature with Glomeruli being affected if enough vessels are affected it can lead to cortical renal stenosis.
What is the fundamental pathogenesis of thrombotic microangiopathies?
Loss of thromboresistance by endothelial cells. (loss of NO and prostacyclin to keep blood flowing freely and liquid) As a result platelets are activated and they aggregate and adhere to vessel walls.
Where would you expect to see HUS?
In a child post infection from SHIGA toxin from diarrheal E. coli H7:0157
What is the cause of TTP?
von Willebrand factor multimers from ADAMTS 13 deficiency
Where does fibrin deposit if there is endothelial damage in the thrombotic microangiopathies?
- Lumen
- Subintima
- Media
In severe cases where there is involvement of larger blood vessels what occurs?
Concentric thickening resembling an onion skin appearance on biopsy
What chemical agents/therapeutic agents can also cause endothelial damage?
- Radiation
- Chem with Cisplatin
- Gemcitabine or bleomycin
- Cyclosporin
Why shouldn’t Calcineurin inhibitors such as Tacrolimus be used for immunosuppression in kidney transplant?
Because they are nephrotoxic
What is the major difference between TMA and DIC?
In PT and PTT are normal in TMA but prolonged in DIC
What subset of patients does HUS primarily affect?
Small children under 5
What is the pathogenesis of thrombosis in HUS?
Endothelial cells bind shiga toxin resulting in endothelial damage with increased production of endothelin and decreased production of NO
How do cell die in HUS?
Internalization of Shiga-toxin
