Thrombotic Thrombocytopenic Purpura (TTP)

Content of This Page

1- Introduction

2- Pathophysiology

3- Clinical Features

4- Investigations

5- Management

6- Differential Diagnosis

7- Complications

8- Prognosis

Introduction

TTP is a rare, life-threatening thrombotic microangiopathy (TMA) characterized by:

  • Thrombocytopenia

  • Microangiopathic haemolytic anaemia (MAHA)

  • Plus potential involvement of the CNS, kidneys, and fever

 

It is considered a medical emergency with high mortality if untreated.

© image from Wikimedia Commons

Pathophysiology

TTP is primarily caused by:

  • Severe deficiency of ADAMTS-13 (<10% activity), due to:

    • Autoantibodies (acquired TTP)

    • Rarely inherited (congenital Upshaw–Schulman syndrome)

-Mechanism:

  • ADAMTS-13 normally cleaves ultra-large von Willebrand factor (vWF) multimers

  • Without it, vWF accumulates → platelet aggregation in microvasculature

  • Leads to widespread platelet-rich thrombi, especially in brain and kidneys

Clinical Features

Classic Pentad (though rarely all present together):

  1. Thrombocytopenia (purpura, bruising)

  2. Microangiopathic haemolytic anaemia (MAHA)

  3. Neurological signs: confusion, seizures, stroke-like symptoms

  4. Renal impairment: mild to moderate

  5. Fever

-Signs of MAHA include:

  • Anaemia

  • Schistocytes on blood film

  • ↑ LDH, ↓ haptoglobin, ↑ indirect bilirubin

Investigations

  • FBC: ↓ Platelets, anaemia

  • Blood film: Schistocytes (fragmented RBCs)

  • Haemolysis markers: ↑ LDH, ↑ bilirubin, ↓ haptoglobin

  • Renal function: May be impaired

  • ADAMTS-13 activity: <10% diagnostic (if available)

 

  • Coombs test: Negative (distinguishes from autoimmune haemolytic anaemia)

Management

Medical emergency – start treatment urgently without waiting for ADAMTS-13 results

First-line:

  • Plasma exchange (PEX) – daily until platelet count and LDH normalize

    • Removes autoantibodies and replenishes ADAMTS-13

Adjuncts:

  • Glucocorticoids (e.g. prednisolone or methylprednisolone)

  • Rituximab (anti-CD20) in relapsing or refractory cases

  • Caplacizumab:

    • Monoclonal antibody that blocks vWF–platelet interaction

    • Shortens time to response, reduces recurrence

– Platelet transfusion is contraindicated unless life-threatening bleeding occurs.

Differential Diagnosis

  • HUS (haemolytic uraemic syndrome) – more renal, less neuro

  • DIC – ↑ PT/APTT, ↓ fibrinogen, ↑ D-dimer

  • Sepsis-related MAHA

  • Malignant hypertension

  • HELLP syndrome (pregnancy)

Complications

  • Stroke

  • Renal failure

  • Cardiac involvement

  • Relapse (seen in up to 40%)

  • Death if untreated (mortality ~90%); with treatment ~10–20%

Prognosis

  • Good with early plasma exchange

  • Long-term follow-up needed for relapse or chronic ADAMTS-13 deficiency

 

  • Monitor platelet count, LDH, and ADAMTS-13 activity

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