Overview

Thrombotic thrombocytopenic purpura (TTP) is a type of microangiopathic haemolytic anaemia characterised by:

Thrombi form in small blood vessels:

  • This consumes platelets leading to thrombocytopenia
  • Thrombi in blood vessels lead to the shearing and rupturing of red blood cells (RBCs)
  • Thrombi deposit in different sites leading to different symptoms, particularly in the central nervous system and causing neurological signs

TTP tends to affect the central nervous system more compared to haemolytic uraemic syndrome (HUS), which affects the kidneys more.

It may be helpful to look at the chapter on Anaemia: Data Interpretation alongside reading this section to help wrap your head around when to suspect what type of anaemia.

ADAMTS-13

TTP is caused by a deficiency in ADAMTS-13, which is thought to be due to an autoimmune cause. ADAMTS-13 normally cleaves von Willebrand factor (vWF) multimers. More multimers increase platelet adhesion and activation leading to thrombi.

Patients generally have a preceding stressor before the symptoms of TTP manifest (such as infection, pregnancy, and some drugs). It may occur idiopathically.

Epidemiology

  • Incidence is 6 per 1,000,000 per year in the UK
  • Prevalence highest >30 years
  • More common in females than males

Risk Factors

  • Black ethnicity
  • Female sex
  • Obesity
  • Pregnancy or post-partum
  • Malignancy
  • HIV
  • Autoimmune disease

Example History

A 45-year-old woman of African ethnicity presents to the emergency department with a loss of consciousness and jerking reported by her partner. She has recently been feeling hot, lethargic, and has been sweaty. She recently gave birth vaginally 3 weeks ago. On examination, her temperature is 38.4ºC, respiratory rate is 19/min, heart rate 89bpm, blood pressure 140/87mmHg and oxygen saturations are 98% on room air.

Investigations:

Haemoglobin:95 g/L(115 – 165 g/L)
Platelets:130 x 109/L(150 – 450 x 109/L)
White blood cells:10.0 x 109/L(3.0 – 10.0 x 109/L)
Sodium:140 mmol/L(135 – 145 mmol/L)
Potassium:5.0 mmol/L(3.5 – 5.3 mmol/L)
Urea:8.1 mmol/L(2.0 – 7.0 mmol/L)
Creatinine:125 µmol/L(55 – 120 µmol/L)
C-reactive protein:15 mg/L<5.0 mg/L

Presentation

Features vary based on where thrombi and microemboli are:

Investigations

All patients

  • Full blood count (FBC):
    • Haemoglobin – reduced
    • Platelets – reduced
    • Reticulocytes – increased
  • Blood film:
    • Schistocytes
  • Urea and electrolytes:
  • General markers of haemolysis:
    • Bilirubin – elevated
    • Lactate dehydrogenase (LDH) – increased
    • Haptoglobins – low
  • Direct Coomb’s test:
  • ADAMTS-13 activity assay:
    • Decreased activity 

Differential Diagnoses

Haemolytic uraemic syndrome (HUS)

  • The kidneys are usually affected more than the central nervous system
  • There is usually associated bloody diarrhoea
  • More common in children
  • Stool toxins may be present

Disseminated intravascular coagulation (DIC)

  • Patients usually have a predisposing serious condition (e.g. sepsis)
  • Coagulation assays may be abnormal:
  • Decreased fibrinogen
  • Increased PT and APTT – usually normal in TTP
  • Increased fibrinogen and degradation products

Immune thrombocytopenic purpura (TTP)

  • Patients do not have central nervous system signs of AKI
  • The blood film does not show schistocytes, only thrombocytopenia

Management

Overview

TTP is a medical emergency, and treatment involves:

  • Plasma exchange
    • This is to remove antibodies against ADAMTS-13 and replace faulty ADAMTS-13
  • Corticosteroids
    • Reduces autoimmune ADAMTS-13 inhibition
  • Rituximab
    • Inhibits B-cell production of antibodies against ADAMTS-13
  • Splenectomy
    • For chronic cases or if patients do not respond to treatment

Platelet transfusions are avoided:

  • This can worsen TTP

Complications

  • CNS involvement – seizures, altered mental state, stroke
  • AKI and chronic kidney disease
  • Myocardial infarction

Prognosis

  • If untreated, the mortality rate of TTP is as high as 95%
  • With treatment, mortality is around 30%
  • Around 1/3 of survivors experience a relapse within the next 10 years

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