What is the treatment for Thrombotic thrombocytopenic purpura (TTP)?

Treatment of Thrombotic Thrombocytopenic Purpura (TTP)

Immediate plasma exchange combined with immunosuppressive therapy is the cornerstone of TTP treatment and must be initiated urgently, as delays significantly increase mortality. 1, 2

Critical Distinction: TTP vs ITP

The provided evidence primarily addresses Immune Thrombocytopenic Purpura (ITP), which is a completely different disease from Thrombotic Thrombocytopenic Purpura (TTP). 3 These are distinct entities requiring fundamentally different management approaches. TTP is a life-threatening thrombotic microangiopathy requiring emergency intervention, while ITP is an autoimmune disorder with different pathophysiology and treatment.

Immediate Management of TTP

First-Line Treatment

Plasma exchange (therapeutic plasma exchange/TPE) must be initiated immediately upon suspicion of TTP, ideally within 24 hours of ICU admission, as this is independently associated with reduced mortality (HR 0.449). 2

• TPE should be performed daily at 50-80 mL/kg per day using fresh frozen plasma until platelet count normalization and resolution of hemolysis 4
• Patients receiving TPE before day 2 in the ICU have significantly lower mortality (HR 0.284) compared to delayed treatment 2
• Corticosteroids (prednisone 0.75 mg/kg twice daily) should be initiated concurrently with plasma exchange 4

Adjunctive Immunosuppression

Rituximab should be administered early in the treatment course, as it is independently associated with dramatically reduced mortality (HR 0.229). 2

• Early rituximab therapy provides superior outcomes compared to delayed or no rituximab use 2
• This represents a significant advancement in TTP management and should be considered first-line adjunctive therapy 2

Novel Targeted Therapy

Caplacizumab is FDA-approved for treatment of acquired TTP in combination with plasma exchange and immunosuppressive therapy. 1

• Dosing: 11 mg IV bolus before first plasma exchange, followed by 11 mg subcutaneous daily after each plasma exchange session, continuing for 30 days after the last plasma exchange 1
• Efficacy: Caplacizumab significantly reduces time to platelet count response and decreases TTP-related death, recurrence, and major thromboembolic events (12.7% vs 49.3%, p<0.0001) 1
• Treatment may be extended in 7-day intervals for up to 28 additional days if ADAMTS13 activity remains suppressed 1
• Caplacizumab works by inhibiting the interaction between ultra-large von Willebrand factor multimers and platelets 5, 6

Diagnostic Confirmation

Severe ADAMTS-13 deficiency (<10 IU/dL) with or without detectable inhibitory autoantibodies confirms TTP diagnosis. 6, 7

• Essential testing includes: complete blood count, peripheral blood smear (looking for schistocytes), lactate dehydrogenase (elevated), haptoglobin (decreased), ADAMTS13 activity level, complete metabolic panel, coagulation studies (typically normal in TTP), and troponin 6, 7
• Do not delay treatment while awaiting ADAMTS-13 results if clinical suspicion is high 7
• The classic pentad (fever, neurologic abnormalities, thrombocytopenia, microangiopathic hemolytic anemia, renal injury) is present in <7% of cases 7

ICU Management Considerations

All TTP patients require ICU-level monitoring due to high risk of severe organ failure and need for intensive supportive care. 5, 4

• Neurologic complications: Occur in 42-58% of cases and may require mechanical ventilation for severe seizures or altered mental status 4
• Cardiac involvement: Associated with higher mortality and requires continuous monitoring 5
• Renal failure: Occurs in approximately 42% of cases but is typically less severe than in hemolytic uremic syndrome 5, 4
• Mechanical ventilation requirement is independently associated with increased mortality (HR 4.103) 2

Prognostic Factors

Older age, sepsis diagnosis, and need for mechanical ventilation are independently associated with higher mortality. 2

• Hospital mortality in the pre-caplacizumab era was 7.6%, but has declined with improved treatments 2
• Immediate TPE and early rituximab are the most modifiable factors associated with improved survival 2
• Delayed TPE is associated with significantly higher costs in addition to worse outcomes 2

Treatment Response Monitoring

• Platelet counts typically exceed 100 G/L after 3-8 cycles of plasma exchange in patients without preexisting hematological abnormalities 4
• Neurological symptoms should resolve with appropriate treatment 4
• Lactate dehydrogenase levels should decline significantly as hemolysis improves 4

Relapse Management

• Relapses occur in some patients between 2 weeks and 5 months after initial episode 4
• Relapsed TTP responds promptly to reinitiation of plasma exchange therapy 4
• The proportion of patients with recurrence in the overall study period was significantly lower with caplacizumab (13% vs 38%, p<0.001) 1

Critical Pitfalls to Avoid

• Do not confuse TTP with ITP - they require completely different treatments; ITP treatments (corticosteroids alone, IVIg, splenectomy) are inadequate for TTP 3
• Do not delay plasma exchange - every hour counts, and delayed treatment significantly increases mortality and healthcare costs 2
• Do not wait for ADAMTS-13 results - initiate treatment based on clinical suspicion 7
• Do not overlook cardiac involvement - this is associated with higher mortality and requires specific monitoring 5