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

Management of Thrombotic Thrombocytopenic Purpura (TTP)

Immediately initiate therapeutic plasma exchange (TPE) combined with corticosteroids as soon as TTP is suspected—this is the cornerstone of treatment and delays increase mortality. 1, 2

Immediate Recognition and Stabilization

• High index of suspicion is critical: TTP diagnosis requires evidence of microangiopathic hemolytic anemia (schistocytes on peripheral smear) plus thrombocytopenia; waiting for the classic pentad (thrombocytopenia, hemolytic anemia, neurological symptoms, renal dysfunction, fever) delays treatment and worsens outcomes 1
• Obtain immediate hematology consultation—delay in identification is associated with increased mortality 1
• Stabilize any critical organ dysfunction before initiating definitive therapy 1
• Do NOT wait for ADAMTS13 results to start treatment—send ADAMTS13 activity level and inhibitor titer immediately, but begin TPE based on clinical suspicion 1

Essential Diagnostic Workup

Obtain these tests immediately while preparing for TPE:

• Peripheral blood smear to confirm schistocytes (mandatory for diagnosis) 1
• ADAMTS13 activity level and inhibitor titer 1
• LDH, haptoglobin, reticulocyte count, bilirubin, urinalysis 1
• Prothrombin time, activated partial thromboplastin time, fibrinogen (to rule out DIC) 1
• Blood group, antibody screen, direct antiglobulin test 1
• Serum creatinine 1
• Consider CT or MRI brain if neurological symptoms present 1
• Drug exposure history (chemotherapy, sirolimus, tacrolimus, oxymorphone, antibiotics, quinine) 1

First-Line Treatment Protocol

Therapeutic Plasma Exchange (TPE)

Begin daily TPE immediately—this is the definitive treatment for acute TTP: 1, 2

• Perform 1-1.5 plasma volumes daily using fresh frozen plasma (FFP) as replacement fluid 3, 4
• Continue daily TPE until platelet count recovers to >150 × 10⁹/L AND LDH normalizes 3, 4
• Once platelet count responds, taper TPE slowly rather than abrupt cessation 1
• The median number of TPE sessions is approximately 13-15 in patients who achieve complete response 3
• TPE achieves complete response in 60-85% of patients with primary TTP 3, 4

Corticosteroids

Administer concurrently with TPE:

• Methylprednisolone 1 g IV daily for 3 days, with the first dose given immediately after the first TPE session 1
• Alternative: Prednisone 1-2 mg/kg/day (oral or IV equivalent) 1
• After initial high-dose therapy, taper steroids over 2-3 weeks if no exacerbation occurs within 3-5 days after stopping TPE 1

Caplacizumab (FDA-Approved Adjunctive Therapy)

For severe or refractory cases, add caplacizumab to TPE and immunosuppression: 2

• FDA-indicated for acquired TTP in combination with plasma exchange and immunosuppressive therapy 2
• Dosing: 11 mg IV bolus before first TPE, then 11 mg subcutaneous daily after each TPE session 2
• Continue for 30 days after stopping daily TPE 2
• If signs of persistent disease (suppressed ADAMTS13 activity) remain, extend treatment in 7-day intervals for maximum 28 days 2
• Caplacizumab reduces TTP recurrence from 38% to 13% and composite endpoint (death/recurrence/thromboembolism) from 49% to 13% 2
• Time to platelet response is significantly shorter with caplacizumab versus placebo 2

Second-Line and Adjunctive Therapies

Rituximab

• Consider rituximab early, especially in severe presentations or inadequate response to TPE 1
• Targets ADAMTS13 autoantibodies in acquired TTP 5
• Complete the full course of rituximab if initiated 1

Refractory TTP Management

If no improvement or worsening despite standard therapy:

• Increase TPE frequency to twice-daily 1, 5
• Add additional immunosuppressive agents: cyclosporine, cyclophosphamide, vincristine, or bortezomib 1, 5
• Consider salvage splenectomy only in truly refractory cases 5

Critical Management Pitfalls to Avoid

Platelet Transfusion

• DO NOT transfuse platelets unless life-threatening hemorrhage (CNS bleeding) occurs—platelet transfusion may worsen microvascular thrombosis 1
• If absolutely necessary for life-threatening bleeding, give 2-3 fold larger-than-usual dose and only with concurrent TPE 1

Fluid Overload

• High-dose plasma infusion (25-30 mL/kg/day) can be used if TPE unavailable, but carries significant risk of fluid overload requiring subsequent switch to TPE 6
• Eight of 19 patients (42%) required switch from plasma infusion to TPE due to fluid overload in one study 6

Central Venous Access Complications

• Central venous catheter required for TPE carries risks of infection and thrombosis 4
• Discuss with blood bank team before any transfusions that a patient with possible TTP is hospitalized 1

Monitoring During Treatment

• Monitor platelet count and LDH daily until normalization 1
• Continue monitoring weekly during steroid taper 1
• Watch for signs of relapse: 13-38% of patients relapse after initial response 2, 4
• Monitor ADAMTS13 activity levels—persistent suppression indicates need for extended caplacizumab therapy 1, 2

Special Considerations

Secondary TTP

• TPE achieves similar response rates in secondary TTP (87%) versus primary TTP (85%), though complete response may be lower (29% vs 74%) 3, 4
• Address underlying cause (malignancy, drugs, autoimmune disease) while treating TTP 1

Prognostic Factors

• Presence of fever is a poor prognostic indicator requiring prolonged TPE treatment 4
• Higher number of TPE sessions correlates with complete response 3
• Mortality without treatment approaches 90%; with appropriate TPE therapy, mortality decreases to 10-20% 3, 5