Thrombotic Microangiopathy Flashcards
(16 cards)
What is Thrombotic Microangiopathy (TMA)?
Small vessel disease of the kidney often associated with thrombotic events.
What are the main causes of Thrombotic Microangiopathy?
- Hemolytic Uremic Syndrome (HUS)
- HELLP Syndrome (Hemolysis Elevated Liver enzyme Low Platelet)
Rheumatological Causes (3 & 4) - Catastrophic Antiphospholipid Syndrome
- Diffuse Scleroderma
- Malignant Hypertension
What are the key features of Hemolytic Uremic Syndrome (HUS)?
Triad:
Thrombocytopenia
Microangiopathic Hemolytic Anemia (MAHA)
Renal failure
What distinguishes Typical from Atypical HUS ?
Typical HUS: Childhood, usually after dysentery; good prognosis
Atypical HUS: Any age, genetic or Sporadic ; poor prognosis with high recurrence risk after transplant
What genetic mutation is commonly associated with Atypical HUS?
Complement factor H mutation (M/C)
Complement factor B mutation (Worst Prognosis)
Complement factor I mutation
Membrane Cofactor P mutation (Best Prognosis)
What is the treatment approach for Typical HUS?
Conservative; often resolves in 5 days after dysentery
What is the treatment for Atypical HUS?
PLEX (Plasma Exchange therapy)
Eculizumab (anti C5 monoclonal antibody)
Immunosuppressants if genetic
Renal transplant (with high risk of recurrence)
Why do schistocytes form in HUS?
RBCs get damaged as they pass through narrowed vessels blocked by platelet plugs formed in small vessels of kidney
What are common blood investigation findings in HUS?
↑ LDH
negative Coombs test
↑ Indirect bilirubin
↓ Haptoglobin
Normal PT/APTT
What is the key peripheral smear finding in HUS?
Schistocytes >2%
How does pre-renal injury differ from acute tubular necrosis in labs and treatment?
Pre-renal: Normal urine output, BUN/Creatinine >20:1, fluids given
ATN: Decreased urine output, BUN/Creatinine <10:1, fluids withheld, tubular injury present
What are the main causes of Atypical HUS?
Genetic (Complement factor H, I, B mutations)
Sporadic (Drug-induced)
How is TTP (Thrombotic Thrombocytopenic Purpura) different from HUS ?
In TTP Neurological symptoms occur but in HUS renal symptoms occur
TTP may accompany with GI Symptoms and Fever
Pathogenesis in genetic Atypical HUS ?
Alternate complement pathway activation is the cause
Which is associated with Low C3 and Normal C4
If Classical pathways are activated like in case of SLE , then Low C3 and Low C4 are present
Toxins causing Typical HUS ?
Shiga toxin (Shigella dysentery)
Shiga like toxin (Enterohemorrhagic E Coli OI57:H7 M/C)
Neuraminidase toxin (Strep Pneumo)
Drugs responsible for Sporadic HUS are ?
Mitomycin
Gemcitabine
Bevacizumab
Calcineurin inhibitors (Tacrolimus, Cyclosporine)
Clopidogrel
Gemcitabine cause immune mediated HUS
