Renal - HUS/TTP

Question 1

What is HUS

Answer 1

Triad ofMAHA - microangioapathic hemolytic anaemiaThrombocytopeniaRenal failure

Question 2

Cuases of HUS

Answer 2

Typical (epidemic) and atypical.Typical - bloody diarrhoeal prodrome with verotoxin producing enterococci - E.coli157 or shigella

Atypical - rare and poorer prognosis	Strep pneumoniae	CMV/HIV	Malignancy	Pregnancy	Drugs - quinine, ciclosporing	Bone marrow/solid organ trasnplant

Question 3

Pathophysiology of HUS

Answer 3

Ingestion of toxin —> bloody diarrhoea due to haemorrhagic colitis
AKI develops due to direct injury of renal vascular endothelium (due to toxin)
Excessive plt aggregation, microvascular thrombi —> AKI
Hypertension and fluid overload common
Atypical - dysregulated complement system - factors H and I deficiency

Question 4

Ix for HUS

Answer 4

Bloods FBC Blood film - reticulocytes, haemolysis, thrombocytopenia Direct Coombs (immune and non immune differentiation) LDH (raised in haemolysis) Hapto U&E, LFT (split bili) Clotting including fibronogen and D dimer HIV and hepatitis Renal screenStool MC&SUrinalysisRenal imaging

Question 5

Manage HUS

Answer 5

ABCDE etc100% oxygenFluid therapy and electrolyte management (GI losses and renal impairment)CVS support/BP controlEarly renal and haem inputCause - cipro for ecoli and shigellaPLEx Recommended in atypical HUS OFten used in typical as cant distinguish to TTP In typical, steroids IvIG and PLex, antiplatelets are NOT beneficial

Question 6

Prognosis of HUS

Answer 6

Mort 3-5%70-85% recover renal functionAtypical poorer25% die and 50% progress to ESRF

Question 7

How is HUS different to TTP

Answer 7

Specturm of same disease processTTP is a pentad, malignant with 90% mort if not treatedThrombocytopeniaMAHARenal impairmentPLUS

Fluctuating neurology (cerebral endotheliam damage)Fever

Clotting normal - DIC is late and ominous

Question 8

Pathology of TTP

Answer 8

Deficient ADAMTS-13 (vWF cleaving protease).May be genetic (lack of enzyme) or acquired (antibody)VWF is large glycoprotein in plasma, binds factor VII and activates and binds platelets in endothelial injuryMade in endothelium as large multimers —> inactivated by cleavage by ADAMTS13TTP - no ADAMT13 —> no cleavage. Lots of plts activationFibrin deposits and thromus propogation —> distal ischaemiaRed cells shread as they pass the fibrin mesh (MAHA)

Question 9

Management of TTP

Answer 9

1) PLex with octaplas (FFP deficient in vWF) Daily for at least 2 days after plts recover >150 Removes antiboides and replaces plasma with plasma containing ADATMS132) high dose methylpred3) rituximab - monoclonal antibody to CD20 found on b cells. used in refractory disease4) low dose Aspirin once plts >505) supportive - red cell transfusion and folate supp during haemolysis Plt transfusions are CI’d - worsend thrombosis Unless major haemorrhage Thromboprophylaxis once plts>?50