Red Book - HUS/TTP

Question 1

What is HUS

Answer 1

Triad of

MAHA - microangioapathic hemolytic anaemia

Thrombocytopenia

Renal 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 screen

Stool MC&S

Urinalysis

Renal imaging

Question 5

Manage HUS

Answer 5

ABCDE etc

100% oxygen
Fluid therapy and electrolyte management (GI losses and renal impairment)
CVS support/BP control

Early renal and haem input

Cause - cipro for ecoli and shigella

PLEx
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 function

Atypical poorer

25% die and 50% progress to ESRF

Question 7

How is HUS different to TTP

Answer 7

Specturm of same disease process
TTP is a pentad, malignant with 90% mort if not treated

Thrombocytopenia
MAHA
Renal impairment

PLUS

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 injury

Made in endothelium as large multimers —> inactivated by cleavage by ADAMTS13

TTP - no ADAMT13 —> no cleavage. Lots of plts activation

Fibrin deposits and thromus propogation —> distal ischaemia

Red 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 ADATMS13

2) high dose methylpred

3) rituximab - monoclonal antibody to CD20 found on b cells.
used in refractory disease

4) low dose Aspirin once plts >50

5) supportive - red cell transfusion and folate supp during haemolysis
Plt transfusions are CI’d - worsend thrombosis
Unless major haemorrhage
Thromboprophylaxis once plts>?50