What are the next steps in managing a patient with a positive multimer test result indicative of Thrombotic Thrombocytopenic Purpura (TTP)?

Management of Thrombotic Thrombocytopenic Purpura (TTP) Following Positive Multimer Test

For patients with a positive multimer test indicating Thrombotic Thrombocytopenic Purpura (TTP), immediate initiation of plasma exchange (PEX) therapy in combination with immunosuppressive therapy and caplacizumab is the recommended first-line management approach. 1

Immediate Management Steps

1. Urgent Hematology Consultation

   • Contact hematology immediately as delay in identification and treatment is associated with increased mortality 2
   • Stabilize the patient and address any critical organ dysfunction

2. Initiate Triple Therapy

   • Plasma Exchange (PEX)

     • Begin PEX as soon as possible according to existing guidelines 2
     • Continue daily PEX until clinical improvement and normalization of platelet count

   • Caplacizumab (CABLIVI)

     • Administer 11 mg IV bolus at least 15 minutes prior to first plasma exchange 1
     • Follow with 11 mg subcutaneous injection after completion of first plasma exchange 1
     • Continue with 11 mg subcutaneous daily during PEX period and for 30 days after last PEX 1

   • Immunosuppressive Therapy

     • Administer methylprednisolone 1g IV daily for 3 days, with first dose after first PEX 2
     • Consider rituximab for refractory cases 2

Diagnostic Confirmation and Monitoring

1. Essential Laboratory Tests

   • Complete blood count with peripheral blood smear (look for schistocytes)
   • ADAMTS13 activity level (confirm before starting treatment if possible, but don't delay therapy)
   • Serum creatinine, LDH, haptoglobin
   • Coagulation profile
   • Blood type and Rh(D) typing

2. Additional Diagnostic Workup

   • Rule out secondary causes:
     • HIV and HCV testing
     • Evaluation for infections (CMV, EBV, parvovirus)
     • Drug history (check for medications associated with TTP)
     • Pregnancy test in women of childbearing age
     • Consider CT/MRI of brain if neurological symptoms present 2

3. Monitoring During Treatment

   • Daily platelet count and hemoglobin
   • LDH levels to monitor hemolysis
   • ADAMTS13 activity levels to guide treatment duration
   • Consider in vitro bleeding time test (Platelet-Stat) to monitor response to plasma exchange 3

Extended Treatment Considerations

1. Treatment Duration

   • If signs of persistent underlying disease (suppressed ADAMTS13 activity <10%) remain after initial treatment course:
     • Extend caplacizumab treatment in 7-day intervals (maximum 28 days) 1
     • Continue PEX until clinical and laboratory parameters normalize

2. Monitoring for Relapse

   • Monitor platelet count closely after discontinuation of therapy
   • Be vigilant for recurrent thrombocytopenia which may indicate relapse
   • In clinical trials, 13% of patients treated with caplacizumab experienced relapse compared to 38% in the placebo group 1

Special Considerations

1. Bleeding Risk

   • Caplacizumab increases bleeding risk; avoid concomitant use of antiplatelet agents or anticoagulants 1
   • Withhold caplacizumab 7 days prior to elective surgery or invasive procedures 1
   • Monitor for signs of bleeding (epistaxis, gingival bleeding, petechiae)

2. Treatment Failure

   • If no response to initial therapy within 4-7 days, consider:
     • Intensifying immunosuppression (e.g., adding cyclophosphamide)
     • Increasing frequency of plasma exchange
     • Adding rituximab if not already started

3. Discontinuation Criteria

   • Discontinue caplacizumab if the patient experiences more than 2 recurrences of TTP while on therapy 1

Clinical Pearls and Pitfalls

• Don't delay treatment: Mortality in untreated TTP approaches 90%; early intervention is critical
• Monitor ADAMTS13 levels: Persistent severe deficiency (<10%) at the end of treatment indicates ongoing immunological disease and risk of relapse 1
• Watch for complications: Neurological symptoms, renal impairment, and cardiac involvement require close monitoring
• Avoid platelet transfusions: Unless life-threatening bleeding is present, as they may worsen microvascular thrombosis

The HERCULES trial demonstrated that caplacizumab in combination with PEX and immunosuppression significantly reduced TTP-related death, recurrence of TTP, and treatment-emergent major thromboembolic events compared to placebo (12.7% vs 49.3%) 1, making this combination the standard of care for managing TTP.