Renal - HUS/ITP

Question 1

What is haemolytic uraemic syndrome (HUS)?

Answer 1

Triad of:1. MAHA2. Thrombocytopenia3. Renal failure/AKI

Question 2

What are the causes of HUS?

Answer 2

1. Infective/epidemic:- bacterial: shiga toxin producing E.coli or Shigella2. Atypical HUS:- Infection: Strep. pneumonia, CMV, HIV- Bone marrow transplant- Drugs: Quinine, ciclosporin- Malignancy- Pregnancy

Question 3

What is the pathophysiology of HUS?

Answer 3

Typical/epidemic HUS:- Toxin ingestion causes bloody diarrhoea from haemorrhage colitis.- AKI is due to direct injury from the toxin to the renal vascular endothelium, leading to platelet aggregation and microvascular thrombi.

Question 4

What investigations would you perform in HUS?

Answer 4

1. Blood tests:- FBC, blood film, haptoglobin, LDH - looking for evidence of thrombocytopenia and haemolytic- direct Coombs test - to exclude immune mediated causes- U&Es - for evidence of AKI- clotting and fibrinogen - to assess for development of DIC.- LFTs including split bilirubin- Stool MC&S- Urinalysis- Renal imaging to exclude obstructive causes- If unable to differentiate between TTP, send ADAMTS 13

Question 5

How would you manage a patient with HUS?

Answer 5

Resuscitate using an ABCDE approach, correcting abnormalities as they are found.Specific management includes:- supportive care:- correction of electrolyte abnormalities- RRT if required- BP support- early renal and haematology input - ?PEx if unsure if aHUS- If infective cause e.g. E.coli treat with ABx - ciprofloxacin- remove any other underlying cause

Question 6

What is the prognosis of HUS?

Answer 6

Epidemic HUS:- low mortality and good renal recovery if treated earlyAtypical HUS:- higher mortality ~25% with ESRF rates of ~50%

Question 7

How does HUS differ clinically from TTP?

Answer 7

Presentation:- TTP there is often significant neurological involvement with presentation ranging from confusion to seizures, coma and cerebrovascular events.- TTP often has fever in its presentationPentad:1. MAHA2. Thrombocytopenia3. AKI4. Neurological impairment5. Fever

Investigations:- Cerebral imaging may show venous or arterial infarcts- Often a more profound thrombocytopenia, anaemia and thrombosis risk- low ADAMTS 13 levelsTreatment:- Early PEx is essential- May require mAb therapy e.g. RituximabPrognosis:- TTP has much higher mortality

Question 8

What is the pathology of TTP?

Answer 8

Deficiency of ADAMTS 13 which is a matrix metalloproteinase which usually cleaves endothelial released vWF inactivating it.Deficiency of ADAMTS 13 leaves large multimer glycoprotein vWF uncleaved, which then causes mechanical haemolysis of red cells and platelet activation leading to: MAHA, low platelets and thrombogenesis.

Question 9

How is TTP managed?

Answer 9

Resuscitate patient in an ABCDE approach correcting abnormalities as they are found.- administed 100% oxygen- support blood pressure - initial fluid resuscitation and vasopressors.Specific treatment includes:- central access/ 2x large bore access and establishment of PEx- request FFP or octaplas for PEx- avoid use of platelets for correction of thrombocytopenia- can give FFP/octaplas whilst awaiting PEx- High dose methyl-prednisolone- Rituximab if refractory to PEx- low dose aspirin and thromboprophylaxis can be given once platelets > 50