🩸 Thrombotic Thrombocytopenic Purpura (TTP) is a rare, life-threatening thrombotic microangiopathy caused by deficiency of the protease ADAMTS13, which normally cleaves von Willebrand factor multimers. Without it, widespread platelet aggregation and microvascular thrombosis occur. ⚠️ Mortality can reach 90% if untreated, but survival exceeds 80–90% with urgent plasma exchange.

⭐ Key Features – The TTP Pentad

Classic Pentad (though all 5 are not always present)
1️⃣ Thrombocytopenia: bleeding, bruising, purpura, epistaxis 2️⃣ Microangiopathic Hemolytic Anaemia (MAHA): fatigue, pallor, jaundice; schistocytes on blood film 3️⃣ Renal dysfunction: proteinuria, haematuria (less severe than in HUS) 4️⃣ Neurological symptoms: headache, confusion, seizures, strokes, TIAs 5️⃣ Fever: sometimes present

🧬 Types

Familial (Upshaw–Schulman): Rare autosomal recessive ADAMTS13 deficiency → accumulation of ultralarge vWF multimers.
Acquired/Sporadic: More common; due to IgG autoantibody inhibiting ADAMTS13. Often triggered by pregnancy, autoimmune disease, infections, stem-cell transplant, or drugs.

⚠️ Causes/Triggers

Pregnancy and postpartum period
Drugs: quinine, clopidogrel, ticlopidine, ciclosporin, tacrolimus
Stem cell transplantation
Autoimmune diseases (e.g., SLE)

🩺 Clinical Features

Bleeding: petechiae, bruising, epistaxis
Neurological: confusion, headache, seizures, TIAs, strokes
Renal: haematuria, proteinuria (usually less severe than HUS)
Constitutional: fever, malaise

🔍 Investigations

FBC: Severe thrombocytopenia + normocytic anaemia
Blood film: Schistocytes (fragmented red cells)
Haemolysis markers: ↑ LDH, ↑ reticulocytes, ↑ unconjugated bilirubin, ↓ haptoglobins
U&E: Raised creatinine/urea (mild–moderate)
Coagulation: PT, APTT, fibrinogen = normal (distinguishes from DIC)
ADAMTS13 activity: Markedly reduced (<10%) in most cases; inhibitors may be detected in acquired TTP.

🔎 Differentials

HUS: Commoner in children, E. coli O157:H7, marked renal failure, normal clotting
DIC: Prolonged PT/APTT, ↓ fibrinogen (unlike TTP)
Meningococcal sepsis: Sepsis picture with coagulopathy
Other: Malignant hypertension, pre-eclampsia, HELLP, SLE, disseminated cancer

💊 Management (Specialist Centre)

🚨 Urgent plasma exchange (plasmapheresis): Removes autoantibodies and replaces ADAMTS13 (cornerstone of treatment).
Corticosteroids: Immunosuppression to reduce autoantibody formation.
Rituximab: Anti-CD20 monoclonal antibody – useful in refractory/relapsing disease.
Caplacizumab: Anti-vWF nanobody that prevents platelet aggregation (reduces early relapse risk).
Supportive care: avoid platelet transfusion unless life-threatening bleeding.

📊 Prognosis

Mortality >90% if untreated.
With urgent treatment: survival rates >80–90%.
Risk of relapse in ~30–40%; requires long-term follow-up.

📚 Teaching Commentary

💡 Exam tip: Always think of TTP when you see MAHA + thrombocytopenia with normal coagulation tests. Early recognition and immediate plasma exchange save lives. Remember: TTP is a haematological emergency – call haematology early.

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Thrombotic Thrombocytopenic purpura (TTP)