What is the treatment for Thrombotic Thrombocytopenic Purpura (TTP)?

Treatment of Thrombotic Thrombocytopenic Purpura (TTP)

Immediate therapeutic plasma exchange (TPE) combined with corticosteroids is the first-line treatment for TTP and must be initiated urgently when TTP is suspected, as untreated TTP has a mortality rate exceeding 90%. 1, 2

Emergency Management

Start TPE immediately upon clinical suspicion of TTP—do not wait for ADAMTS13 results, as delays in treatment are fatal. 1, 3, 2

First-Line Therapy

• Daily therapeutic plasma exchange (TPE) using fresh frozen plasma (FFP) to supplement ADAMTS13, remove anti-ADAMTS13 autoantibodies, and clear unusually large von Willebrand factor multimers 1, 2
• High-dose corticosteroids administered concurrently with TPE to suppress autoantibody production 1, 4, 2
  • Typical regimen: methylprednisolone 1-2 mg/kg/day or equivalent 4
• Caplacizumab (anti-VWF A1 domain nanobody) is now recommended as first-line therapy in Japan alongside TPE and corticosteroids, as it directly inhibits platelet-VWF binding and prevents microthrombi formation 1, 2

Critical Distinction from ITP

Platelet transfusions are relatively contraindicated in TTP due to thrombosis risk—this is the opposite of immune thrombocytopenic purpura (ITP) where platelet transfusions are used for life-threatening bleeding 5

Refractory or Relapsing Disease

When patients show suboptimal response to initial TPE and corticosteroids (occurring in 15-20% of cases), escalate treatment aggressively: 4, 6

Second-Line Options

• Rituximab (anti-CD20 monoclonal antibody) is the most important second breakthrough in TTP management after TPE, with high response rates in refractory cases 1, 6, 2
  • Now routinely recommended during acute phase for suboptimal responders 6
  • Increasingly used as frontline therapy in severe presentations 6
• Twice-daily TPE instead of once-daily for more aggressive disease 6
• Cyclophosphamide plus vincristine for immunosuppression in relapsing patients 4, 6
  • In one series, all four relapsing patients achieved complete remission with cyclophosphamide plus vincristine added to TPE 4

Salvage Therapy

• Splenectomy reserved for desperate cases with refractory disease 6
• Bortezomib and N-acetylcysteine are under evaluation as emerging therapies 6

Congenital TTP (cTTP)

For patients with ADAMTS13 gene mutations rather than autoantibodies: 1, 2

• Fresh frozen plasma (FFP) infusion to supplement ADAMTS13 (not full plasma exchange, as there are no autoantibodies to remove) 1
• Recombinant human ADAMTS13 is a promising treatment currently under development 6, 2

Relapse Prevention

Monitor ADAMTS13 activity during remission—persistent severe ADAMTS13 deficiency (<10%) predicts high relapse risk (approximately 40% of patients relapse) 6, 2

• Preemptive rituximab should be considered when ADAMTS13 activity remains severely reduced despite clinical remission 6
• Relapse timing varies: can occur as early as one week or as late as months after initial remission 4

Common Pitfalls

• Never delay TPE while awaiting ADAMTS13 results—clinical suspicion alone (thrombocytopenia + microangiopathic hemolytic anemia) warrants immediate treatment 3, 2
• Do not confuse with ITP—the treatment approaches are fundamentally different, particularly regarding platelet transfusions 5
• Rule out disseminated intravascular coagulation (DIC), heparin-induced thrombocytopenia, and medication-induced effects before diagnosing postoperative TTP 3
• Recognize that 60% of idiopathic TTP patients may show non-specific positive ANA titers (≥1:40)—this does not indicate lupus-induced TTP 4