What is the management of Thrombotic Thrombocytopenic Purpura (TTP)?

Management of Thrombotic Thrombocytopenic Purpura (TTP)

The first-line treatment for acquired TTP is immediate therapeutic plasma exchange (TPE) in combination with immunosuppressive therapy, with consideration of caplacizumab in patients with severe disease. 1

Clinical Presentation and Diagnosis

TTP is characterized by:

• Microangiopathic hemolytic anemia
• Severe thrombocytopenia
• Organ ischemia due to microvascular platelet-rich thrombi
• Neurological symptoms (in many cases)
• Renal dysfunction

Diagnostic workup should include:

• Complete blood count with peripheral smear (look for schistocytes)
• ADAMTS13 activity level and inhibitor titer
• LDH, haptoglobin, reticulocyte count, bilirubin
• Prothrombin time, activated partial thromboplastin time, and fibrinogen
• Blood group and antibody screen, direct antiglobulin test
• Urinalysis
• Consider brain imaging (CT/MRI) and cardiac evaluation (ECG, echocardiogram)

Management Algorithm

Immediate Management

1. Hematology consultation - Should be called immediately as delay in identification is associated with increased mortality 2
2. Initiate daily therapeutic plasma exchange (TPE) - The cornerstone of treatment that has transformed the historically fatal prognosis to current survival rates >80% 3
3. Immunosuppressive therapy - Start corticosteroids (methylprednisolone 1g IV daily for 3 days) 1

Based on Disease Severity

For Grade 4 TTP (Life-threatening consequences):

• Daily TPE with further exchanges dependent on clinical progress
• Methylprednisolone 1g IV daily for 3 days, with first dose after first TPE
• Consider caplacizumab if ADAMTS13 activity level is normal with inhibitor or elevated anti-ADAMTS13 IgG 1, 4
• Consider rituximab for patients with suboptimal response to initial therapy 3

For Refractory Disease:

• Intensify to twice-daily TPE 1, 3
• Add rituximab - Now routinely recommended during acute phase for suboptimal responders 3
• Consider additional immunosuppressive agents such as cyclophosphamide, vincristine, or cyclosporine A 1, 5
• Consider splenectomy in desperate cases 3, 5

Monitoring Response

• Monitor platelet count, hemoglobin, LDH, and clinical symptoms daily
• Perform serial ADAMTS13 measurements during TPE to guide treatment decisions in complicated cases 2
• For patients with initial platelet count response, discontinue TPE if no exacerbation within 3-5 days 1

Maintenance and Relapse Prevention

• Taper steroids over 2-3 weeks after TPE discontinuation 1
• Complete course of rituximab if initiated 1
• Discontinue caplacizumab if initiated 1, 4
• Consider maintenance rituximab for relapse prevention in patients with severe acquired ADAMTS13 deficiency 3

Emerging Therapies

Several promising therapies are in development:

• Recombinant ADAMTS13 - Enzyme replacement therapy that may provide better outcomes than plasma therapy 6
• N-acetylcysteine - Currently under evaluation in clinical trials 5

Important Considerations

1. High index of suspicion is critical for early diagnosis and treatment initiation
2. Relapses occur in up to 40% of patients despite initial successful treatment 3
3. Mortality risk is highest within the first days of management 3
4. Long-term follow-up is crucial to identify other autoimmune diseases, control relapses, and evaluate psychophysical sequelae 5
5. Serial ADAMTS13 measurements during treatment can guide management decisions in complicated cases 2

Caplacizumab Specifics

Caplacizumab has been shown to significantly reduce:

• Time to platelet count response
• TTP-related deaths (0% vs 4.1% with placebo)
• TTP recurrence during treatment (4.2% vs 38.4% with placebo)
• Overall recurrence rate in the study period (13% vs 38% with placebo) 4

The recommended dosing is:

• 11mg IV bolus prior to first plasma exchange
• 11mg SC daily after completion of each plasma exchange
• Continue for duration of daily TPE and for 30 days thereafter 4

By implementing this comprehensive approach to TTP management, mortality has been reduced from nearly 90% to less than 20%, with further improvements expected as newer therapies become available.