TTP and HUS

Question 1

definition of TTP and HUS

Answer 1

Triad of microangiopathic haemolytic anaemia, acute renal failure and thrombocytopaenia.

There are two forms:

1. D+ (diarrhoea-associated form);
2. D- (no prodromal illness identified).

Question 2

relationship between TTP and HUS

Answer 2

Haemolytic uraemic syndrome overlaps with thrombotic thrombocytopenic purpura (TTP) which has the additional features of fever and fluctuating CNS signs.

Question 3

aetiology of TPP and HUS

Answer 3

congenital deficiency of, or acquired Ab to, the ADAMTS13 protease which normally cleaves multimers of vWF

something causes endothelial injury = platelet aggregation, release of unusually large vWF multimers and activation of plts and clotting cascade

= small vessel thrombosis and fibrin deposition in small vessels, particularly the glomerular-afferent arteriole and capillaries, which undergo fibrinoid necrosis = renal ischemia and acute renal failure

the thrombi promote intravascular haemolysis

ie there is multisystem microangiopathy

Question 4

provoking factors of TTP and HUS

Answer 4

infection

• Verotoxin-producing Escherichia coli0157 (from contaminated water, meat, dairy products) - especially in children
• Shigella,
• neuraminidase-producing infections (e.g. pneumococcal respiratory tract infection),

HIV

drugs - OCP, ciclosporin, mitomycin, 5-flurouracil

malignant hypertension

malignancy

pregnancy

SLE

scleroderma

atypical HUS caused by dysregulation/uncontrolled activation of complement

Question 5

epidemiology of TTP and HUS

Answer 5

uncommon

D+ haemolytic uraemic syndrome often affects young children, occurs more often in summer in epidemics and is the most common cause of acute renal failure in children.

TTP mainly affects adult females.

Question 6

sx of TTP and HUS

Answer 6

GI - Severe abdominal colic, watery diarrhoea that becomes bloodstained.

General: Malaise, fatigue, nausea, fever<38C (D+ form).

renal - oliguria or anuria, haematuria

Question 7

signs of TTP and HUS

Answer 7

general

• pallor from anaemia
• slight jaundice - from haemolysis
• bruising - severe thrombocytopenia
• generalised oedema
• hypertension
• retinopathy

GI - abdo tenderness

CNS signs especially in TTP - weakness, reduced vision, fits, reduced consciousness

Question 8

Ix for TTP and HUS

Answer 8

blood

urine

stool samples - light and electron microscopy, culture

renal biopsy

ADAMTS13 activity

evidence of shiga toxin producing E coli

look for abnormalities in the complement pathway - C3, C4, factors H and I, complement mutation screen

Question 9

blood results in TTP and HUS

Answer 9

FBC - normocytic anaemia, high neutrophils, v low platelets

UE - high urea, creatinine, urate K and low Na

clotting - normal Plt, APTT and fibrinogen levels - abnormality might indicate DIC

LFT - increased unconjugated BR, high LDH from haemolysis

low haptoglobin

fragments on blood film

blood cultures

ABG - low pH, low bicarb, low PaCO2, normal anion gap

Question 10

urine results in TTP and HUS

Answer 10

>1g protein/24h,

haematuria,

fractional excretion NA+ >1%

Question 11

renal biopsy results in TTP and HUS

Answer 11

Contraindicated in severe thrombocytopaenia.

D+ form: Arteriolar necrosis, glomerular capillary thrombosis.

D- form: Intimal proliferation in arterioles.

Question 12

pentad of TTP

Answer 12

microangiopathic haemolytic anaemia

low platelets

AKI

neurological sx - headache, palsies, seizure, confusion, coma

fever

Question 13

triad of HUS

Answer 13

microangiopathic haemolytic anaemia

acute renal failure - haematuria/proteinuria

thrombocytopenia