Treatment of TTP Exacerbation
Immediately initiate therapeutic plasma exchange (TPE) upon suspicion of TTP exacerbation, without waiting for ADAMTS13 results, as delay increases mortality. 1
Immediate Emergency Management
First-Line Treatment Protocol
- Start TPE at 1-1.5 times plasma volume daily using fresh frozen plasma as replacement fluid 1
- Administer the first TPE session as soon as possible—this is the single most critical intervention for survival 1, 2
- Continue TPE daily until platelet count exceeds 150,000/mm³ and LDH normalizes, then taper slowly 1
Concurrent Corticosteroid Therapy
- Administer methylprednisolone 1g IV daily for 3 days starting immediately after the first TPE session 1
- Follow with prednisone 1-2 mg/kg/day 1
- Continue corticosteroids throughout the TPE period to suppress autoantibody production 3
Caplacizumab (CABLIVI) Administration
- Add caplacizumab 11 mg IV bolus at least 15 minutes prior to the first plasma exchange 4
- Follow with 11 mg subcutaneous injection daily after each plasma exchange session 4
- Continue 11 mg subcutaneous daily for 30 days after the last plasma exchange 4
- If signs of persistent disease (suppressed ADAMTS13 activity) remain, extend treatment for up to 28 additional days 4
- Caplacizumab significantly reduces TTP recurrence during treatment (4.2% vs 38.4% with placebo) and TTP-related mortality 4
Management of Refractory or Severe Cases
When to Escalate Therapy
- Add rituximab 375 mg/m² weekly for 3-4 weeks if the patient fails to respond adequately to initial TPE and corticosteroids 1, 5
- Consider twice-daily TPE in patients with severe neurological symptoms or life-threatening manifestations 5
- Vincristine or cyclophosphamide may be added as salvage therapy in desperate cases 5, 6
Critical Pitfalls to Avoid
- Never delay TPE while waiting for ADAMTS13 results—clinical suspicion alone warrants immediate treatment 1
- Avoid platelet transfusions unless life-threatening bleeding is present, as they may worsen thrombosis 1
- Avoid antiplatelet agents and anticoagulants during caplacizumab therapy due to increased bleeding risk 4
- Do not use anti-D immunoglobulin in TTP exacerbations, as it is only indicated for immune thrombocytopenia (ITP), not TTP 3
Special Considerations for Plasma Allergies
- If the patient has a history of anaphylactic reactions to plasma, substitute with Octaplas (solvent/detergent-treated pooled plasma) 7
- Alternatively, use albumin with slowly increasing amounts of standard plasma to mitigate allergic risks 7
Monitoring During Treatment
- Monitor platelet count and LDH daily to assess response 1
- Check ADAMTS13 activity levels at the end of treatment—if <10%, the patient remains at high risk for relapse and may require extended caplacizumab therapy 4
- Provide folic acid 1 mg daily supplementation 1
- Transfuse red blood cells conservatively, targeting hemoglobin 7-8 g/dL in stable patients 1
Duration and Discontinuation
- Continue daily TPE until platelet count normalizes (>150,000/mm³) and LDH normalizes 1
- Taper TPE slowly rather than stopping abruptly to prevent early relapse 1
- Discontinue caplacizumab if the patient experiences more than 2 recurrences of TTP while on therapy 4
- Withhold caplacizumab 7 days prior to any elective surgery or invasive procedures due to bleeding risk 4
Key Outcome Data
The combination of TPE, corticosteroids, and caplacizumab achieves complete remission in approximately 89% of patients, with significantly reduced recurrence rates compared to TPE and corticosteroids alone 4, 2. Time to platelet recovery is shortened with caplacizumab, and the composite endpoint of TTP-related death, recurrence, or major thromboembolic events is reduced from 49.3% to 12.7% 4.