Synopsis
Recognise thrombotic microangiopathy before the classic pentad, send ADAMTS13 correctly, start plasma exchange, corticosteroid and caplacizumab urgently, and prevent relapse through immune surveillance.
- TTP is a thrombotic microangiopathy caused by severe ADAMTS13 deficiency, usually from an acquired autoantibody and rarely from biallelic inherited variants.
- Without ADAMTS13 cleavage, ultra-large von Willebrand factor multimers capture platelets in small vessels, causing organ ischaemia, thrombocytopenia and red-cell fragmentation.
- Most patients do not present with the historic pentad; thrombocytopenia and microangiopathic haemolytic anaemia without another clear cause should trigger immediate action.
- Schistocytes, raised LDH, low haptoglobin, indirect bilirubin and reticulocytosis support haemolysis, while routine coagulation is often normal unlike DIC.
- Neurological fluctuation, headache, confusion, seizure, focal deficit, myocardial injury and abdominal pain can occur despite only modest creatinine elevation.
- A pre-treatment ADAMTS13 activity below 10% strongly confirms TTP; inhibitor or antibody studies distinguish acquired immune disease from congenital deficiency.
- Use a validated clinical score such as PLASMIC to estimate severe ADAMTS13 deficiency while awaiting the assay, but never let scoring delay the TTP centre.
- Daily plasma exchange replaces ADAMTS13 and removes antibody, corticosteroid suppresses autoimmunity, and caplacizumab rapidly blocks von Willebrand factor–platelet interaction.
- Rituximab is commonly added early in immune TTP to suppress antibody production and reduce relapse; hepatitis B screening and infection planning are required.
- After clinical remission, serial ADAMTS13 activity can identify biochemical relapse before thrombocytopenia and guide pre-emptive specialist treatment.
Key red flags
Thrombocytopenia, fragments and haemolysis with normal routine coagulation requires immediate TTP service contact and treatment.
Investigation priorities
Confirm platelet consumption and red-cell fragmentation.
Management branches
Thrombocytopenia and microangiopathic haemolysis occur without a clear alternative cause.
- Call the regional TTP team, assess brain, heart, kidneys, abdomen and bleeding and calculate a validated probability score without delaying transfer.
- Send pre-plasma ADAMTS13, inhibitor and TMA samples according to the reference laboratory instructions while preserving treatment urgency.
- Start daily plasma exchange, corticosteroid and caplacizumab under the specialist pathway and avoid prophylactic platelet transfusion.
Key medicines
CaplacizumabGive the licensed 10 mg intravenous dose before plasma exchange then 10 mg subcutaneously after each exchange and daily after exchange for the protocol-defined period, extended if immune activity persists.Mucocutaneous and major bleeding, procedures and concomitant antithrombotics require review; continuing after exchange depends on ADAMTS13 and specialist assessment.
RituximabThe TTP centre uses an intravenous induction regimen scheduled around plasma exchange, commonly 375 mg/m² weekly for four doses, with premedication and infection screening.Screen hepatitis B, immunoglobulins and vaccine needs; infusion reaction, infection, late neutropenia and impaired vaccine response require follow-up.