Medication Summary
The therapy of choice is plasma exchange with fresh frozen plasma and immunosuppression.
In January 2019 the FDA approved caplacizumab (Cablivi) for adults with acquired thrombotic thrombocytopenic purpura (aTTP), in combination with plasma exchange and immunosuppressive therapy. It has been shown to reduce time to platelet count response and also to reduce aTTP-related death, recurrence, or major thromboembolic events. [5]
The chemotherapeutic agent vincristine has been used as an adjunct to plasma exchange in patients with refractory disease, but its routine use has not been validated. Case reports have suggested that cyclosporine may be beneficial in patients with refractory disease even though this drug has been incriminated as a potential trigger of TTP. [30] Although used in the past, aspirin and dipyridamole are no longer used in treating TTP.
The anti-CD20 monoclonal antibody rituximab has been reported to have activity in TTP that is refractory to plasma exchange. A study by Scully et al found that weekly rituximab given within 3 days of acute admission for TTP was safe and effective, with reduced stay and relapse. [31] A study by Froissart and colleagues, in 22 adult patients who had responded poorly to plasma exchange, found that treatment with rituximab resulted in shorter overall treatment duration and reduced 1-year relapses, compared with historical controls. [22]
Rituximab is typically given in a dosage of 375 mg/m2 weekly for 4 weeks. Ideally, at least 4 hours should elapse between administration of rituximab and plasma exchange. [16]
Monoclonal antibody
Class Summary
These agents have shown efficacy in the treatment of autoimmune disorders. Caplacizumab has been shown to reduce time to platelet count response and also to reduce aTTP-related death, recurrence, or major thromboembolic events. [5]
Caplacizumab (Cablivi, caplacizumab-yhdp)
Antibody fragment that targets the A1-domain of von Willebrand factor (vWF), and inhibits the interaction between vWF and platelets; thereby, reducing both vWF-mediated platelet adhesion and platelet consumption. It is indicated for aTTP in combination with plasma exchange and immunosuppressive therapy.
Rituximab (Rituxan)
Anti-CD20 chimeric monoclonal antibody initially approved for therapy of follicular lymphoma. Has been shown to have activity in several autoimmune disorders such as immune thrombocytopenia, systemic lupus erythematosus, autoimmune hemolytic anemia, and rheumatoid arthritis.
Blood Products
Class Summary
Plasma exchange with FFP is the therapy of choice for TTP.Fresh frozen plasma (FFP, Octaplas)
Fresh frozen plasma (FFP, Octaplas)
Plasma provides all plasma proteins and clotting factors to support adequate hemostasis to treat or prevent bleeding or to treat other protein deficiencies that cannot be replaced with protein specific concentrates. It is indicated for plasma exchange in patients with TTP. Octaplas is a solvent detergent treated, pooled FFP.
Chemotherapy agents
Class Summary
These agents are used as an adjunct to plasma exchange.
Vincristine (Oncovin, Vincasar)
Mechanism of action uncertain. May involve a decrease in reticuloendothelial cell function or increase in platelet production. However, neither of these mechanisms fully explains the effect in TTP and HUS.
Corticosteroids
Class Summary
These agents are used to treat idiopathic and acquired autoimmune disorders. They are also used as an adjunct to plasma exchange.
Prednisone (Sterapred)
May work by decreasing activity of reticuloendothelial system. In light of the evidence that patients with acquired TTP have an inhibitor to vWF-cleaving protease, steroids may decrease production of autoantibody.
-
Differential diagnosis of immune thrombocytopenia (ITP), thrombotic thrombocytopenic purpura (TTP), and disseminated intravascular coagulation (DIC).
