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

Plasma Exchange Treatment for Thrombotic Thrombocytopenic Purpura (TTP)

Plasma exchange (PEX) should be initiated immediately in adults with suspected TTP while awaiting ADAMTS13 test results, especially if the PLASMIC score indicates intermediate-to-high risk of TTP. 1

Diagnosis and Initial Assessment

• TTP is characterized by:

  • Microangiopathic hemolytic anemia
  • Severe thrombocytopenia
  • Organ ischemia due to microvascular platelet-rich thrombi
  • Severely deficient ADAMTS13 activity (<10%)

• Use PLASMIC score to assess probability of TTP:

  • Platelet count < 30 × 10⁹/L
  • Hemolysis markers present
  • Absence of active cancer
  • Absence of solid organ/stem cell transplant
  • MCV < 90 fL
  • INR < 1.5
  • Creatinine < 2.0 mg/dL

Treatment Algorithm

First-Line Treatment

1. Immediate plasma exchange:

   • Exchange 1-1.5 times plasma volume daily 2
   • Use fresh frozen plasma as replacement fluid
   • Continue daily until platelet count normalizes (>150 × 10⁹/L) and LDH normalizes 2
   • Then gradually taper frequency

2. Concurrent therapy:

   • High-dose corticosteroids (1-2 mg/kg/day prednisone) 1
   • Consider rituximab early in treatment course 1, 3

Treatment Monitoring

• Monitor platelet count, hemoglobin, LDH, and clinical symptoms daily
• Measure ADAMTS13 activity serially during treatment to guide management decisions 4
• Continue plasma exchange until clinical remission is achieved

Refractory or Unresponsive TTP

If no improvement or clinical deterioration occurs:

1. Intensify plasma exchange to twice daily 5
2. Add rituximab if not already started 1
3. Consider adding caplacizumab (von Willebrand factor inhibitor) 1, 3

Special Considerations

Adults vs. Children

• In adults: Start plasma exchange immediately upon suspicion of TTP
• In children: TTP is less common; acceptable to defer plasma exchange for 24-48 hours until ADAMTS13 results confirm diagnosis 1

TTP in Lupus Nephritis

• Management approach is similar but requires co-management with hematology
• Treatment includes plasma exchange, high-dose glucocorticoids, rituximab, and/or caplacizumab 1

Catastrophic Antiphospholipid Syndrome

• Can present with similar features to TTP
• Plasma exchange has been associated with improved survival in retrospective studies 1
• Consider additional anticoagulation therapy

Treatment Efficacy and Outcomes

• Plasma exchange has dramatically improved survival rates in TTP from nearly 0% to approximately 85-93% 3, 2
• Higher number of plasma exchange sessions correlates with better complete response rates 2
• Combination of plasma exchange with corticosteroids may reduce mortality compared to plasma exchange alone 2

Potential Complications and Monitoring

• Monitor for complications of plasma exchange:

  • Bleeding
  • Hypotension
  • Catheter-related infections
  • Electrolyte abnormalities
  • Transfusion reactions

• Long-term follow-up is essential to:

  • Monitor for relapses (occur in ~16% of patients) 3
  • Regular monitoring of ADAMTS13 activity during remission
  • Identify development of other autoimmune diseases

Pitfalls to Avoid

• Delaying plasma exchange while awaiting definitive diagnosis can be fatal
• Failing to consider concurrent conditions (e.g., heparin-induced thrombocytopenia) when response is suboptimal 4
• Premature discontinuation of plasma exchange before adequate clinical response
• Not monitoring ADAMTS13 activity during treatment and follow-up

Plasma exchange remains the cornerstone of TTP management and should be initiated promptly in any patient with suspected TTP, as delays in treatment can significantly increase mortality.