Fogo, Ch. 11 - Thrombotic MIcroangiopathies

Question 1

Distinguish clinically between TTP and HUS.

Answer 1

TTP: Affects adults. Fever, bleeding, anemia, AKI, and neurologic impairment.

HUS: Affects children. Anemia, AKI, and thrombocytopenia.

Question 2

What are some mild findings in thrombotic microangiopathies?

Answer 2

Fibrin platelet thrombi in glomeruli and/or arterioles (more common in children)

Mesangiolysis and mesangial “unraveling”

Question 3

What are some severe findings in thrombotic microangiopathy?

Answer 3

Segmental cortical and arterial necrosis, RBC fragments.

Question 4

What are the LM findings that correlate to ischemic change?

Answer 4

GBM corrugation

Tuft retraction & collapse

Question 5

What are the IF/EM findings in TMAs?

Answer 5

Non-specific immunofluorescence (IgM/C3, fibrin/fibrinogen)

Swollen endothelium, fibrin tactoids, mesangiolysis, and GBM breakdown.

Question 6

What is the etiology of diarrhea-associated (D+) HUS?

Answer 6

Shiga-like or verotoxin from shigella or O157:H7 attaches to kidney Gb3 (via beta-subunit) and inactivates the 60S ribosomal subunit (via alpha-subunit)

Question 7

What is the etiology of non-diarrhea associated (D-) atypical HUS? How is it treated?

Answer 7

Probably related to defects in factor H, I, or membrane cofactor protein resulting in unregulated complement activation.

Treat with plasmapheresis, transplant, eculizumab.

Question 8

What are some familial and iatrogenic causes of TMA?

Answer 8

Familial: Deficiency of ADAMTS13 (results in long abnormal vWF multimers)

Drugs: Cyclosporine, mitomycin, anti-VEGF

Question 9

How can TTP be distinguished from HUS?

Answer 9

ADAMSTS13 is not severely reduced in (at least D+) HUS.

Question 10

Recall some prognostic factors in TMAs.

Answer 10

Children tend to do better.

Adults may suffer lasting renal injury (worse with segmental or cortical necrosis or PAI-1 abnormality).