Thrombotic Thrombocytopenic Purpura

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy from severe ADAMTS13 deficiency (activity below 10%), leading to ultra large von Willebrand factor multimers and platelet-rich microthrombi.

• Immune TTP (iTTP, acquired): anti-ADAMTS13 autoantibodies; incidence 3 per million; women, Black patients; associated with HIV, SLE, pregnancy, drugs.

• Congenital TTP (Upshaw-Schulman): ADAMTS13 mutations, pregnancy and infection triggers.

• Mortality 90% untreated, under 10% with treatment.

• Relapse in 30 to 40% of iTTP.

• Severe thrombocytopenia with bleeding (petechiae, purpura), fever, microangiopathic haemolytic anaemia, neurological symptoms (headache, confusion, seizures, stroke), renal dysfunction (usually mild), cardiac involvement (troponin elevation, arrhythmia, sudden death).

• Abdominal pain, ischaemia.

• The classic pentad is rarely complete.

• Platelets usually under 30 x 10^9/L, schistocytes, raised LDH, bilirubin, reticulocytes, low haptoglobin, negative DAT, normal coagulation, creatinine.

• PLASMIC score (high probability 6 to 7): platelets under 30, haemolysis, no active cancer, no transplant, MCV under 90, INR under 1.5, creatinine under 2.0.

• ADAMTS13 activity (under 10%) and inhibitor/IgG before plasma exchange; troponin, ECG, brain imaging, HIV, ANA, pregnancy test.

• Distinguish from STEC and complement HUS, DIC, HELLP, malignant hypertension.

Begin within hours on clinical suspicion (high PLASMIC score), before ADAMTS13 returns.

• Daily therapeutic plasma exchange (1 to 1.5 plasma volumes using fresh frozen plasma or cryosupernatant) until platelets above 150 x 10^9/L for 2 consecutive days; if exchange is delayed, infuse plasma 30 mL/kg/day.

• Prednisolone 1 mg/kg/day (or methylprednisolone 1 g IV daily for 3 days) for the first weeks then taper.

• Rituximab 375 mg/m2 weekly for 4 doses (start early; reduces relapse).

• Caplacizumab 10 mg IV loading before first exchange then 10 mg SC daily during exchange and for 30 days after (or until ADAMTS13 above 20%), reducing time to platelet recovery, exacerbation and refractoriness; monitor bleeding.

• Avoid platelet transfusion unless life threatening haemorrhage.

• Refractory: bortezomib 1.3 mg/m2, ciclosporin, mycophenolate, splenectomy, N-acetylcysteine.

• Congenital TTP: prophylactic plasma infusion 10 to 15 mL/kg every 2 to 3 weeks or recombinant ADAMTS13 (40 IU/kg every 2 weeks).

• Folic acid 5 mg daily, thromboprophylaxis with LMWH when platelets above 50, aspirin 75 mg.

• Remission monitoring: ADAMTS13 monthly initially then every 3 months; pre-emptive rituximab when activity falls below 20%.

• Pregnancy counselling and contraception choice.