Makindo Medical Notes

🩸 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

🧬 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.