What is the diagnosis and treatment for Thrombotic Thrombocytopenic Purpura (TTP)?

From the Guidelines

Thrombotic thrombocytopenic purpura (TTP) is a rare but life-threatening blood disorder requiring immediate treatment with plasma exchange (PEX) and corticosteroids, as delay in identification is associated with increased mortality/morbidity 1. The standard first-line therapy for TTP includes:

• Plasma exchange (PEX) at 1-1.5 plasma volumes daily until platelet count normalizes and hemolysis resolves, typically for at least 2-3 days after platelet recovery
• Corticosteroids, such as methylprednisolone 1g/day IV for 3 days, then prednisone 1mg/kg/day
• Caplacizumab (10mg IV loading dose followed by 10mg subcutaneous daily) may be added to prevent relapses
• Rituximab (375mg/m² weekly for 4 weeks) is often added for acquired TTP to prevent relapses Patients should be monitored with daily CBC, LDH, and ADAMTS13 activity levels. Supportive care includes:
• Avoiding platelet transfusions unless life-threatening bleeding occurs, as they can worsen microvascular thrombosis
• Stabilizing any critical organ dysfunction The first step in the management of TTP is a high index of suspicion for the diagnosis and timely recognition, with immediate hematology consult, as delay in identification is associated with increased mortality/morbidity 1. TTP results from severe deficiency of ADAMTS13, an enzyme that cleaves von Willebrand factor, leading to platelet aggregation and microvascular thrombosis. Without treatment, mortality exceeds 90%, but with prompt therapy, survival rates exceed 80-90% 1.

From the FDA Drug Label

The efficacy of CABLIVI for the treatment of adult patients with acquired thrombotic thrombocytopenic purpura (aTTP) in combination with plasma exchange and immunosuppressive therapy was established in a pivotal multicenter, randomized, double-blind, placebo-controlled trial (HERCULES) Patients received a single 11 mg CABLIVI bolus intravenous injection or placebo prior to the first plasma exchange on study, followed by a daily subcutaneous injection of 11 mg CABLIVI or placebo after completion of plasma exchange, for the duration of the daily plasma exchange period and for 30 days thereafter

The diagnosis of Thrombotic Thrombocytopenic Purpura (TTP) is not directly stated in the provided text, but the treatment for acquired TTP is:

• Caplacizumab (CABLIVI) in combination with
• Plasma exchange and
• Immunosuppressive therapy The recommended dosage is an initial 11 mg intravenous bolus injection followed by 11 mg daily subcutaneous injections for the duration of plasma exchange and for 30 days thereafter 2.

From the Research

Diagnosis of Thrombotic Thrombocytopenic Purpura (TTP)

• TTP is characterized by thrombocytopenia, hemolytic anemia, fever, renal dysfunction, and neuropsychiatric symptoms 3, 4, 5
• Reduced activity of a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) below 10% is a diagnostic criterion for TTP 4, 5
• TTP can be classified as immune-mediated TTP (iTTP) if the patient is positive for anti-ADAMTS13 autoantibodies, and as congenital TTP (cTTP) if ADAMTS13 gene abnormalities are detected 4

Treatment of Thrombotic Thrombocytopenic Purpura (TTP)

• Therapeutic plasma exchange (TPE) and immunosuppressive therapy are the mainstays of treatment for TTP 3
• Corticosteroids have been used for immunosuppressive therapy, and current drug therapies include rituximab and caplacizumab 3, 4, 6, 7
• Caplacizumab, an anti-von Willebrand factor (VWF) nanobody, inhibits the binding of platelets to VWF and prevents microthrombi formation 3, 4, 6, 7
• Recombinant human ADAMTS13 is a promising treatment for cTTP 3
• Fresh frozen plasma (FFP) transfusion is performed in patients with cTTP to supplement ADAMTS13, and plasma exchange therapy using FFP is conducted in patients with iTTP to supplement ADAMTS13 and to remove anti-ADAMTS13 autoantibodies and unusually large VWF multimers 4
• Immunomodulatory therapies, including corticosteroids, rituximab, and other agents, should be considered to eliminate autoantibodies for a sustained remission 5

Special Considerations

• In cases where patients have anaphylaxis to fresh-frozen plasma, caplacizumab may be used safely and effectively without concomitant plasma exchange 7
• ICI-related acquired TTP requires awareness, and low ADAMTS13 activity can be used to diagnose TTP and support the need for plasma exchange 6
• Treatment for ICI-related acquired TTP includes combinations of rituximab and caplacizumab, corticosteroids, and plasma exchange 6