Thrombotic Thrombocytopaenic Purpura (TTP)

TTP is a thrombotic microangiopathy caused by ADAMTS13 activity <10%, leading to platelet-rich microvascular thrombi. The classic pentad (MAHA, thrombocytopaenia, neurological features, fever, renal impairment) is not always complete — MAHA +…

BSH TTP Diagnostic and Treatment Algorithm

The pathway

1 · Recognise and suspect TTP

Microangiopathic haemolytic anaemia (MAHA): schistocytes on blood film, Hb <100g/L, raised LDH, low haptoglobin, raised bilirubin
Thrombocytopaenia (<30 × 10⁹/L typical)
Neurological features: confusion, seizures, stroke
Screen: FBC, blood film, LDH, haptoglobin, bilirubin, reticulocytes, Coombs test (negative in TTP), ADAMTS13 activity

2 · Send ADAMTS13 before treatment

ADAMTS13 activity <10% confirms TTP — send before first plasma exchange
Also send ADAMTS13 inhibitor titre
Blood film for schistocytes is an emergency — call haematology same day
Do NOT delay plasma exchange awaiting ADAMTS13 result if high clinical suspicion

3 · Plasma exchange (PEX) — start urgently

1.5x plasma volume exchange daily using FFP as replacement fluid
Start within 4–8 hours of diagnosis
Continue daily until platelet count >150 × 10⁹/L for 2 consecutive days and LDH normalising
Coordinate with haematology and ITU/apheresis unit

4 · Prednisolone

Prednisolone 1mg/kg/day (max 60mg) PO from diagnosis
Continue until platelet remission, then wean
Reduces autoantibody production

5 · DO NOT transfuse platelets

Platelet transfusion is contraindicated in TTP
Can precipitate arterial thrombosis and death
Only consider if life-threatening haemorrhage AND after senior haematology authorisation

6 · Caplacizumab

Caplacizumab 10mg IV before the first plasma exchange, then 10mg SC daily after each exchange
Start alongside first PEX if anti-vWF therapy available
Indicated in refractory disease or relapse
Blocks platelet–vWF interaction; continue for 30 days after last PEX

7 · Rituximab for refractory/relapse

Rituximab 375mg/m² IV weekly × 4 doses (or low-dose rituximab 100mg per BSH 2023 protocol)
For refractory TTP (failure to respond after 5 PEX) or relapse
Depletes B cells → reduces ADAMTS13 autoantibody

8 · Monitor for response

Daily FBC, LDH, blood film
Target: platelets >150 × 10⁹/L, LDH normal, no neurological features
Watch for exacerbation within 30 days of stopping PEX — recheck ADAMTS13

Drugs

Drug	Dose	Route	Notes
Fresh Frozen Plasma (FFP)	1.5x plasma volume daily	IV (via apheresis)	Replacement fluid for plasma exchange. Provides ADAMTS13 and removes inhibitor. Coordinate with apheresis unit.
Prednisolone	1mg/kg/day (max 60mg)	PO	Start at diagnosis. Wean after platelet remission. Monitor glucose and BP.
Caplacizumab	10mg — IV first dose, then 10mg SC daily	IV/SC	10mg throughout, not 11. IV before the first plasma exchange; SC after each exchange, including that first day. Continue 30 days after the last exchange. Monitor for bleeding — anti-vWF effect.
Rituximab	375mg/m² or 100mg flat dose	IV	For refractory or relapsed TTP. Weekly × 4. Pre-medicate with paracetamol + antihistamine.
Folic acid	5mg OD	PO	Supportive — compensates for haemolytic demand on folate stores.

When to escalate

Neurological deterioration (seizures, reduced GCS) despite ongoing plasma exchange,Platelet count <10 × 10⁹/L with active haemorrhage — discuss platelet transfusion with haematology,Failure to achieve platelet remission after 5–7 plasma exchange sessions (refractory TTP),ADAMTS13 <10% on repeat testing after completion of treatment course (relapse risk),Haemodynamic instability or acute kidney injury requiring ITU-level care,Exacerbation within 30 days of stopping plasma exchange — restart PEX, consider caplacizumab

Reference: BSH Guideline for the Diagnosis and Management of TTP 2023

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