TTP – Treatment

Overview

• According to condition:
  • Management of patients with suspected primary immune TTP:
    • Treat TTP as a medical emergency.
    • Initiate:
      • Therapeutic plasma exchange (TPE)
      • Corticosteroids
    • Consider:
      • Addition of rituximab to TPE and corticosteroids
      • Addition of caplacizumab to TPE and immunosuppressive therapy
    • If TPE is unavailable or will be delayed, consider large plasma infusions (25-30 mL/ kg), if tolerated, in conjunction with pulsed methylprednisolone.
  • Management of patients with secondary TTP and ADAMTS13 activity < 10%:
    • Treat with standard therapy that is recommended for primary TTP.
    • Treat the underlying condition.
  • Management of refractory TTP:
    • In patients with refractory immune TTP or have severe ADAMTS13 deficiency despite the addition of rituximab treatment, consider another immunosuppressive therapy.
    • For some patients, an increase in the frequency of TPE (for example, increasing frequency to twice per day) may be needed.
  • Management of relapsing TTP (an episode of acute TTP beginning > 30 days after completing plasma exchange for a previous TTP episode):
    • Restart plasma exchange and corticosteroids.
    • Consider the addition of rituximab to corticosteroids and TPE, if not given already,
    • Consider administering caplacizumab.
  • Management of congenital TTP:
    • ADAMTS13 prophylaxis should be individualized according to the patient’s phenotype.
    • For an acute episode of congenital TTP, BSH recommends solvent/detergent-treated plasma infusion or an administration of ADAMTS13-containing intermediate purity factor VIII.
    • ADAMTS13, recombinant-krhn (Adzynma) is FDA approved for prophylactic or on demand enzyme replacement therapy (ERT) in adults and pediatric patients with congenital thrombotic thrombocytopenia purpura.
  • Management of patients who are pregnant:
    • If the TTP episode presents for the first time during pregnancy, initially manage the patient with plasma exchange and corticosteroids as per immune TTP in the non-pregnant state.
    • In patients with immune TTP, if the TTP is refractory to plasma exchange and corticosteroids or TTP relapses, consider additional treatments such as cyclosporine, azathioprine, and rituximab.
    • In patients with congenital TTP, administer solvent/detergent-treated plasma infusions to prevent a clinical TTP relapse.
  • Platelet transfusion should be avoided. (BSH, 1B)
• According to treatment paradigm:
  • Removal of UL-VWFM:
    • Therapeutic plasma exchange (TPE)
  • Removal of anti-ADAMTS13 autoantibodies:
    • TPE
  • Suppression of production of anti-ADAMTS13 autoantibodies:
    • Immunosuppressants:
      • Corticosteroids
      • Anti-CD20 antibodies:
        • Rituximab
        • Ofatumumab
        • Obinutuzumab
      • Bortezomib
      • Daratumumab
  • Inhibition of platelet/VWF thrombus:
    • Caplacizumab¹
  • ADAMTS13 supplementation:
    • TPE
    • FFP infusion
    • Recombinant human ADAMTS13

Expert opinion

• Liu S and Zheng XL, 2023
  • “When a patient with highly suspected or confirmed iTTP based on clinical presentation (e.g., severe thrombocytopenia, microangiopathic hemolytic anemia and organ injury) or ADAMTS13 activity less than 10 units/dL, a combination of TPE, caplacizumab, and immunosuppressive (e.g., corticosteroids, rituximab, etc.), known as the triple therapy, should be given as early as possible”.
  • “As soon as the clinical diagnosis is made, emergent TPE should be initiated, followed by early caplacizumab and b and corticosteroids”.
  • “Rituximab, an anti-CD20 monoclonal antibody, should be prescribed to patients as early as possible to halt the
    production of anti-ADAMTS13 autoantibodies”.
• Gounder P and Scully M, 2024:
  • iTTP in pregnancy:
    • Acute TTP is treated with plasma exchange
    • Corticosteroids are safe in pregnancy and can be given concurrently
    • The use of rituximab and caplacizumab, while not absolutely contraindicated in pregnancy, has potential risks:
      • Rituximab targets fetal B lymphocytes and may increase the risk of infection.
      • Caplacizumab may cross the placenta and cause an acquired von Willebrand disease, with a risk fetal or neonatal bleeding.
    • “The decision to deliver depends on maternal safety, and fetal maturity and well-being, and requires a multidisciplinary approach.”
  • Congenital TTP (cTTP) in pregnancy:
    • The use of recombinant ADAMTS13 (rADAMTS13) is associated with improved maternal and fetal outcome in cTTP.
    • Recombinant ADAMTS13 in cTTP can achieve higher ADAMTS13 activity levels and avoid regular hospital attendance for plasma therapies.

What the clinical practice guidelines say