What is the primary treatment for a patient diagnosed with Thrombotic Thrombocytopenic Purpura (TTP)?

Primary Treatment for Thrombotic Thrombocytopenic Purpura (TTP)

The primary treatment for TTP is immediate therapeutic plasma exchange (TPE) combined with immunosuppressive therapy, specifically corticosteroids, with the addition of caplacizumab when available to reduce mortality and recurrence. 1, 2

Immediate Initiation of Plasma Exchange

Therapeutic plasma exchange must be started immediately upon suspicion of TTP, as untreated TTP has a mortality rate exceeding 90%. 2 The critical determinant of outcome is timely diagnosis and initiation of life-saving TPE therapy. 3

TPE Protocol Specifications

• Perform daily TPE at 1-1.5 times plasma volume using fresh frozen plasma (FFP) as replacement fluid. 4, 5
• Continue daily TPE until platelet count recovers to >150 × 10⁹/L and serum LDH normalizes, then slowly taper. 4, 5
• The median number of TPE sessions required for complete response is approximately 13-15 sessions. 5
• Complete response rates with TPE reach 85% in both primary and secondary TTP. 5

Alternative When TPE Unavailable

• If TPE is not immediately available, high-dose plasma infusion (25-30 mL/kg per day) may be used as a temporizing measure. 6
• However, be aware that fluid overload occurs frequently with plasma infusion, often necessitating subsequent switch to TPE. 6

Concurrent Immunosuppressive Therapy

Corticosteroids should be administered concurrently with TPE from the outset. 2 While some studies show no statistical advantage of TPE plus corticosteroids versus TPE alone in terms of complete response rates (82.1% vs. 76.7%), mortality rates are significantly lower with combined therapy (3% vs. 14%). 5

Corticosteroid Options

• Prednisone or high-dose methylprednisolone are the standard corticosteroid choices. 2
• The combination of corticosteroids with TPE reduces mortality compared to TPE alone. 5

Addition of Caplacizumab (CABLIVI)

Caplacizumab is FDA-approved for treatment of acquired TTP in combination with plasma exchange and immunosuppressive therapy and should be added when available. 1

Caplacizumab Dosing Protocol

• Administer 11 mg IV bolus prior to the first plasma exchange. 1
• Follow with 11 mg subcutaneous injection daily after each plasma exchange session. 1
• Continue for the duration of daily plasma exchange plus 30 days thereafter. 1
• If signs of persistent disease (suppressed ADAMTS13 activity) remain, extend treatment in 7-day intervals for maximum 28 additional days. 1

Caplacizumab Efficacy Data

• Time to platelet count response is significantly shorter with caplacizumab compared to placebo. 1
• The composite endpoint of TTP-related death, recurrence, or major thromboembolic events occurs in only 12.7% with caplacizumab versus 49.3% with placebo (p<0.0001). 1
• Recurrence of TTP during treatment period is reduced from 38.4% to 4.2% with caplacizumab. 1

Rituximab Consideration

Rituximab, an anti-CD20 antibody, is effective in newly diagnosed cases, refractory cases, and for relapse prevention. 2 While not first-line, it should be considered early in the treatment course, particularly for severe or refractory cases.

Critical Diagnostic Requirements

TTP diagnosis requires the presence of both thrombocytopenia and microangiopathic hemolytic anemia—these two criteria are mandatory. 5 Once these are identified, TPE should be initiated immediately without waiting for additional confirmatory testing. 5, 3

Common Clinical Pitfalls

• Do not delay TPE while awaiting ADAMTS13 results—treatment must begin on clinical suspicion alone. 3, 2
• Fever is a poor prognostic indicator requiring prolonged TPE treatment. 4
• Fluid overload is the most common complication when plasma infusion is used instead of TPE, occurring in approximately 30% of patients. 6
• Central venous catheter complications (infection, thrombosis) occur in TPE patients and require vigilant monitoring. 6

Treatment Algorithm Summary

1. Suspect TTP based on thrombocytopenia plus microangiopathic hemolytic anemia 5, 3
2. Immediately initiate daily TPE (1-1.5 plasma volumes with FFP) 4, 5
3. Simultaneously start corticosteroids (prednisone or methylprednisolone) 5, 2
4. Add caplacizumab 11 mg IV bolus before first TPE, then 11 mg SC daily 1
5. Continue daily TPE until platelets >150 × 10⁹/L and LDH normalizes, then taper 4, 5
6. Continue caplacizumab for 30 days after stopping daily TPE 1
7. Consider rituximab for severe, refractory, or relapsing cases 2