Thrombotic Thrombocytopenic Purpura

Question 1

Definition

Answer 1

HUS overlaps with TTP (thrombotic thrombocytopenia purpura), which has 2
additional features to make a pentad:
o Fever
o Fluctuating CNS/neurological signs

HUS is characterised by a triad of:
o Microangiopathic haemolytic anaemia (MAHA)
o Thrombocytopenia
o Acute renal failure

Question 2

Association with HUS

Answer 2

• Many consider TTP and HUS as a spectrum of disease
• All with TTP have HUS, along with the additional features
• Even though HUS and TTP are similar, they have DIFFERENT aetiologies that lead to MAHA

Question 3

Aetiology

Answer 3

• In TTP, there is deficiency of a protease (ADAMTS-13) that normally cleaves vWf –
which causes build-up of the large multimers of vWf → platelet aggregation and
fibrin deposition → thrombocytopenia and microthrombi

Question 4

Causes (drugs)

Answer 4

• COCP
• Ciclosporin
• Mitomycin
• Quinine
• 5-fluorouracil
• Some chemotherapy/targeted cancer drugs eg monoclonal antibodies, TKIs

Question 5

Causes (other)

Answer 5

• Malignant hypertension
• Malignancy
• Bone marrow transplant – both
• Pregnancy / post-partum – both
• SLE
• Scleroderma
• Genetic predisposition for atypical HUS – FHx of HUS
• Antiplatelets eg clopidogrel, toclopidine – TTP
• Autoimmune damage against ADAMTS-13 – TTP

Question 6

Risk factors

Answer 6

HIV

Obesity

Question 7

Epidemiology

Answer 7

UNCOMMON

TTP mainly affects ADULT FEMALES (20-59 years) + is more common in BLACK people

Question 8

Presenting symptoms (GI)

Answer 8

o Severe abdominal colic
o Watery diarrhoea, esp bloody (prodrome for STEC HUS) – diagnosis occurs 5-10
days post onset

• TTP may have a non-specific prodrome
o TTP: N&V, diarrhoea, abdominal pain – microthrombi in bowel

Question 9

Presenting symptoms (general)

Answer 9

o Malaise
o Fatigue
o Nausea
o Fever < 38 degrees (D+ or TTP)

Question 10

Presenting symptoms (renal)

Answer 10

o Oliguria or anuria

o Haematuria

Question 11

Signs on physical examination (for both HUS and TTP)

Answer 11

• General
o Pallor
o Slight jaundice (due to haemolysis)
o Bleeding: bruising/purpura/ecchymoses, menorrhagia
o Generalised oedema
o Hypertension
o Retinopathy

• GI
o Abdominal tenderness

Question 12

Signs on physical examination (just TTP)

Answer 12

CNS Signs – TTP only
o Mild: headache, confusion
o Coma
o Focal abnormalities
o Weakness
o Reduced vision
o Fits / seizures
o Reduced consciousness

Question 13

Investigations (bloods)

Answer 13

FBC
o Normocytic anaemia (low Hb) – haemolysis
o High neutrophils
o Very low platelets – thrombocytopenia 
o High reticulocytes in TTP!!

Question 14

Investigations (U&Es)

Answer 14

o High urea
o High creatinine
o High K+
o Low Na+
o Electrolyte abnormalities may be due to diarrhoea (in HUS) and AKI

Question 15

Investigations (LFTs)

Answer 15

o High unconjugated bilirubin
o High LDH from haemolysis
o Evaluate hepatic involvement in STEC HUS (may have raised ALT/AST)

Question 16

Investigations (other)

Answer 16

• Haptoglobin – decreased during haemolysis
• LDH – high during haemolysis (released from RBC)

• ABG
o Low pH (due to bicarbonate loss)
o Low bicarbonate
o Low PaCO2
o Normal anion gap

• Blood Film
o Schistocytes / fragments
o High reticulocytes and spherocytes

• Direct Coombs’ test – to exclude AIHA

• Urinalysis/dipstick
o 1+ g protein/24 hrs – mild proteinuria
o Haematuria

• Blood cultures – presence of STEC
• Stool culture – presence of STEC (may be -ve if not done early in diarrhoeal illness); MC&S
• PCR – to detect Shiga toxin 1/2

• Proteins involved in complement regulation – abnormal levels of complement (eg low
C3/C4) in familial and atypical HUS

• ADAMTS-13 level – deficiency in TTP!!!!
• Serum amylase, lipase and glucose – ev