What is the treatment for ADAMTS13 (A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13) deficiency associated with thrombotic thrombocytopenic purpura (TTP)?

Treatment of ADAMTS13 Deficiency in Thrombotic Thrombocytopenic Purpura (TTP)

The treatment for ADAMTS13 deficiency associated with TTP requires immediate plasma exchange plus glucocorticoids, with the addition of rituximab and/or caplacizumab in severe cases. 1

Diagnostic Approach

Before initiating treatment, confirm the diagnosis with:

• ADAMTS13 activity level and anti-ADAMTS13 antibodies
• Complete blood count with peripheral smear (look for schistocytes)
• LDH, haptoglobin, reticulocyte count, bilirubin
• Coagulation studies (PT, aPTT, fibrinogen)
• PLASMIC score to assess risk of TTP

Treatment Algorithm Based on ADAMTS13 Activity

For Low ADAMTS13 Activity (<10%) - Confirmed TTP:

1. First-line treatment:

   • Immediate plasma exchange (PEX) - 1-1.5 times plasma volume daily until remission
   • High-dose glucocorticoids (methylprednisolone 1g IV daily for 3 days, then prednisone 1 mg/kg/day)

2. Additional therapies for severe/refractory cases:

   • Rituximab (anti-CD20 monoclonal antibody)
   • Caplacizumab (von Willebrand factor inhibitor) - 11mg IV bolus before first PEX, then 11mg SC daily during and 30 days after PEX 2

For Normal ADAMTS13 Activity:

• Evaluate for other thrombotic microangiopathy etiologies
• Test for antiphospholipid antibodies
• Consider complement-mediated TMA

Special Considerations

• Congenital vs. Acquired TTP:

  • Congenital TTP (ADAMTS13 mutations): Regular plasma infusions
  • Acquired TTP (autoantibodies): PEX, immunosuppression, caplacizumab

• Monitoring Response:

  • Platelet count recovery
  • Reduction in LDH levels
  • Improvement in clinical symptoms
  • ADAMTS13 activity levels

• Duration of Therapy:

  • Continue PEX until platelet count >150,000/μL for at least 2 consecutive days
  • Continue caplacizumab for 30 days after last PEX
  • Extended treatment may be needed if ADAMTS13 activity remains suppressed 1

Emerging Therapies

Recent research indicates potential benefit from:

• Recombinant ADAMTS13 replacement therapy 3
• ADAMTS13-loaded platelets for targeted delivery
• ADAMTS13-encoding mRNA therapy

Important Caveats and Pitfalls

• Delay in treatment initiation significantly increases mortality - don't wait for ADAMTS13 results before starting PEX in suspected cases
• Avoid platelet transfusions unless life-threatening bleeding (may worsen microvascular thrombosis)
• Monitor for PEX complications (catheter-related infections, thrombosis, TRALI)
• Discontinue caplacizumab if patient experiences more than 2 recurrences of TTP while on therapy 2
• Withhold caplacizumab 7 days before elective procedures to reduce bleeding risk 2

Treatment of Refractory or Relapsing TTP

For patients not responding to standard therapy:

1. Intensify immunosuppression (higher dose steroids, additional rituximab)
2. Consider twice-daily plasma exchange
3. Add caplacizumab if not already using
4. Consider eculizumab for complement-mediated TMA 1
5. Evaluate for clinical trial eligibility for novel therapies

The key to successful management is rapid diagnosis and prompt initiation of plasma exchange with appropriate immunosuppression, as this approach has reduced mortality from nearly 90% to less than 20% in patients with TTP.