Thrombotic microangiopathy - TTP vs HUS mechanism (ADAMTS13 deficiency)
Core concept
- TMA = thrombocytopenia + microangiopathic haemolytic anaemia + organ ischaemia, from platelet-rich microthrombi in arterioles and capillaries
- Red cells fragment on turbulent flow past partly occluded vessels -> schistocytes
- inc LDH, dec haptoglobin, inc unconjugated bilirubin, DAT negative
- Exception: pneumococcal-associated HUS can be DAT positive (neuraminidase exposes the T antigen)
- PT, APTT and fibrinogen are normal - this is the discriminator from DIC
Two mechanisms
- TTP - ADAMTS13 deficiency (<10%)
- Ultra-large VWF multimers are not cleaved -> spontaneously bind platelets -> VWF-platelet thrombi
- Brain and heart worst hit; kidney relatively spared
- Immune (autoantibody, ~95% of adult cases) or congenital (Upshaw-Schulman)
- HUS - endothelial injury
- STEC-HUS: Shiga toxin binds Gb3 on glomerular endothelium -> ribosome inactivation -> cell death
- aHUS: unregulated alternative complement pathway on the endothelial surface
3 more sections, plus exam facts
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