Thrombotic thrombocytopenic purpura (TTP)

Question 1

Define Thrombotic thrombocytopenic purpura (TTP)

Answer 1

Pentad of MAHA, acute renal failure/AKI, thrombocytopenia, fever and fluctuating CNS signs

Question 2

Aetiology of Thrombotic thrombocytopenic purpura (TTP)

Answer 2

Aetiological factor causes endothelial injury that results in platelet aggregation, release of unusually large vWF multimers and activation of platelets and the clotting cascade.
Results in small vessel thrombosis (particularly the glomerular-afferent arteriole and capillaries) → fibrinoid necrosis → renal ischaemia → acute renal failure
Thrombi → intravascular haemolysis

May be due to lack of ADAMTS-13 (vWF-cleaving enzyme)

Infection: E. coli 0157 (contaminated water, meat, dairy) | shigella | neuraminidase-producing infections e.g. pneumococcal respiratory tract infection | HIV
Drugs: OCP | Ciclosporin |mitomycin | 5-fluorouracil
Others: Malignant hypertension | malignancy | pregnancy | SLE | scleroderma

Question 3

Risk Factors for Thrombotic thrombocytopenic purpura (TTP)

Answer 3

Black ethnicity 
Female
Obesity 
Pregnancy 
Cancer therapies
HIV, bone marrow transplant, antiplatelet agents, quinine

Question 4

Epidemiology of Thrombotic thrombocytopenic purpura (TTP)

Answer 4

Higher in women and black people

Very rare

Question 5

Symptoms of Thrombotic thrombocytopenic purpura (TTP)

Answer 5

Anaemia: Lethargy, SOB
Jaundice
Easy bruising
Fever
GI: severe abdominal colic, water diarrhoea (blood stained), abdominal tenderness
Renal: oliguria/anuria, Haematuria, swelling
Eyes: retinopathy
CNS: weakness, reduced vision, seizures, reduced consciousness

Question 6

Signs of Thrombotic thrombocytopenic purpura (TTP)

Answer 6

Pallor
Jaundice
Bruising
Abdominal tenderness
Oedema
Fever
Hypertension 
CNS: weakness, reduced vision, seizures, reduced consciousness

Question 7

Investigations Thrombotic thrombocytopenic purpura (TTP)

Answer 7

FBC: normocytic anaemia | raised neutrophils | haptoglobin reduced | thrombocytopenia
Blood film: Schistocytes | Raised reticulocytes | spherocytes

Urinalysis: proteinuria >1g, haematuria, fractional excretion
Stool sample: detect SHEC

U+Es: raised urea, creatinine, urate, K+
Clotting: normal Plt, APTT, fibrinogen
LFTs: unconjugated bilirubin, LDH raised
LDH: increased, haptoglobin reduced
DAT/Coomb’s test: NEGATIVE (rule out AIHA)

Renal biopsy: D+ - arteriolar necrosis, glomerular capillary thrombosis, intimal proliferation. D- intimal proliferation in arterioles