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

Treatment of Thrombotic Thrombocytopenic Purpura (TTP)

Daily therapeutic plasma exchange (TPE) is the cornerstone of TTP treatment and should be initiated immediately upon diagnosis to reduce mortality from 90% to approximately 10-15%.

Diagnosis and Initial Assessment

• TTP is characterized by:
  • Thrombocytopenia
  • Microangiopathic hemolytic anemia
  • Often accompanied by fever, neurological abnormalities, and renal dysfunction
  • Deficiency of ADAMTS13 enzyme (acquired or congenital)

First-Line Treatment

Immediate Intervention

• Therapeutic Plasma Exchange (TPE):
  • Exchange 1-1.5 times the patient's plasma volume
  • Use fresh frozen plasma (FFP) as replacement fluid
  • Perform daily until normalization of serum LDH and platelet count recovery to >150×10⁹/L 1
  • Continue until clinical improvement, then slowly taper

Adjunctive Therapy

• Corticosteroids:
  • High-dose corticosteroids (e.g., methylprednisolone 1g/day or prednisone 1-2 mg/kg/day)
  • Studies show significant improvement in mortality when combined with TPE compared to TPE alone 1

Treatment Algorithm for TTP

1. Immediate TPE initiation upon suspicion of TTP (don't wait for ADAMTS13 results)
2. Daily TPE sessions until:
   • Platelet count >150×10⁹/L
   • LDH normalizes
   • Clinical symptoms resolve
3. Taper TPE gradually once remission achieved:
   • Every other day for 1 week
   • Twice weekly for 2 weeks
   • Once weekly for 2 weeks
4. Monitor closely for exacerbations during tapering

Management of Refractory TTP

For patients not responding to initial TPE and corticosteroids:

1. Intensify TPE:

   • Increase frequency to twice daily
   • Increase volume of exchange

2. Add Rituximab:

   • 375 mg/m² weekly for 4 weeks
   • Particularly effective for acquired TTP with anti-ADAMTS13 antibodies 2

3. Consider additional immunosuppression:

   • Cyclophosphamide
   • Cyclosporine A
   • Mycophenolate mofetil

4. Newer therapies:

   • Caplacizumab (anti-vWF nanobody) for refractory cases 2

Special Considerations

• Central line infections: Actively seek and treat infections, particularly Staphylococcus aureus, as they can trigger TTP relapse 3
• Platelet transfusions: Generally avoided unless life-threatening bleeding (may worsen microvascular thrombosis)
• Red blood cell transfusions: Provide as needed for symptomatic anemia

Monitoring During Treatment

• Daily complete blood counts
• LDH levels
• Renal function
• Neurological status
• Signs of bleeding or thrombosis

Prognosis and Long-term Management

• Complete response rates of approximately 85% with appropriate TPE 1
• Higher mortality in secondary TTP compared to primary TTP
• Monitor for relapse, which occurs in approximately 20-30% of patients
• Long-term follow-up with regular ADAMTS13 activity monitoring

Pitfalls to Avoid

• Delaying TPE initiation while waiting for confirmatory tests
• Premature discontinuation of TPE
• Failure to recognize and treat underlying causes in secondary TTP
• Overlooking central line infections that can trigger relapse
• Inappropriate platelet transfusions that may worsen microvascular thrombosis

TPE remains the mainstay of TTP treatment with excellent remission and survival rates when initiated promptly 4. The addition of corticosteroids to TPE significantly improves outcomes compared to TPE alone 1.