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

Treatment of Thrombotic Thrombocytopenic Purpura (TTP)

Plasma exchange therapy combined with corticosteroids is the first-line treatment for acquired TTP and should be initiated immediately upon diagnosis to reduce mortality. 1, 2

Diagnosis of TTP

TTP is characterized by:

• Microangiopathic hemolytic anemia (MAHA)
• Severe thrombocytopenia
• Reduced ADAMTS13 activity (<10%)
• Organ dysfunction (neurological symptoms, renal impairment)

Key diagnostic criteria:

• Laboratory findings: thrombocytopenia, schistocytes on blood smear, elevated LDH, decreased haptoglobin
• ADAMTS13 activity <10% confirms the diagnosis
• Anti-ADAMTS13 autoantibodies indicate acquired TTP
• ADAMTS13 gene mutations indicate congenital TTP

Treatment Algorithm for TTP

First-Line Treatment

1. Plasma Exchange (PEX)

   • Initiate immediately upon clinical suspicion, don't wait for ADAMTS13 results
   • Exchange 1-1.5 plasma volumes daily using fresh frozen plasma (FFP)
   • Continue daily until platelet count normalizes (>150,000/μL) and LDH normalizes for at least 2 consecutive days 1, 3

2. Corticosteroids

   • Administer concurrently with plasma exchange
   • Prednisone 1-2 mg/kg/day or methylprednisolone 125-1000 mg/day 2, 3
   • Continue until clinical remission, then taper

Second-Line Treatment (for refractory or relapsed cases)

1. Rituximab

   • 375 mg/m² weekly for 4 weeks
   • Consider as early intervention in severe cases or those with high anti-ADAMTS13 titers 1, 2, 4

2. Caplacizumab

   • Anti-VWF nanobody that blocks platelet-VWF interaction
   • Reduces time to platelet count normalization and risk of early recurrence
   • Increases bleeding risk (17% higher than placebo) 4, 5
   • Continue until ADAMTS13 activity normalizes

Third-Line Options (for refractory cases)

• Increased plasma exchange frequency (twice daily)
• Cyclophosphamide
• Vincristine
• Cyclosporine
• Bortezomib
• N-acetylcysteine
• Splenectomy (rarely used now) 2, 5

Special Considerations

Congenital TTP

• FFP infusion (10-15 mL/kg) every 2-3 weeks
• No need for plasma exchange or immunosuppression 1

Monitoring and Follow-up

• Monitor platelet count, hemoglobin, LDH, and organ function daily during acute phase
• Regular ADAMTS13 activity monitoring during remission
• Preemptive rituximab when ADAMTS13 activity falls below 20% reduces relapse risk by 91% 4

Pregnancy-Associated TTP

• Higher risk of relapse during pregnancy
• Requires close monitoring of ADAMTS13 activity
• May need prophylactic plasma exchange or FFP infusions 5

Prognosis

• Untreated TTP has >90% mortality
• With prompt treatment, survival rates exceed 90%
• Approximately 16% of patients experience at least one relapse 4
• Long-term neurological and cardiovascular sequelae may occur despite treatment

Pitfalls and Caveats

• Delayed diagnosis and treatment significantly increase mortality
• Don't wait for ADAMTS13 results to initiate plasma exchange if clinical suspicion is high
• Platelet transfusions are contraindicated unless life-threatening bleeding occurs, as they may worsen microvascular thrombosis
• Distinguish from other thrombotic microangiopathies (HUS, DIC, HELLP syndrome)
• Regular ADAMTS13 monitoring after remission is crucial to prevent relapses

TTP is a medical emergency requiring immediate intervention with plasma exchange and immunosuppression to prevent mortality. The addition of rituximab and caplacizumab has significantly improved outcomes in recent years.