Treatment protocol for New Onset Immune Thrombotic Thrombocytopenic Purpura (iTTP)
If a diagnosis of iTTP is suspected, then after sending the confirmatory testing (ADAMTS-13 activity and antibody or inhibitor titer), the USTMA strongly recommends immediate initiation of PLASMA EXCHANGE (PEX). PEX should be initiated while awaiting the result of ADAMTS-13 activity. A pending ADAMTS13 activity should not delay the initiation of PEX if iTTP is suspected.
Plasma infusion (Fresh Frozen Plasma) at 25-30 mL/kg can be used as a temporizing measure if there is going to be an unavoidable delay in treatment. However, PEX initiation remains the preferred initial treatment.
The first step in management is the immediate initiation of PLASMA EXCHANGE (PEX), which serves to remove the autoantibody and supplement ADAMTS13 activity. The PEX process can be either performed by centrifugation with continuous or intermittent flow or by membrane based depending on the preferred method of each institution. Fresh frozen plasma (FFP) should be the initial replacement fluid during PEX.
PEX is initiated at 1.0 X plasma volume (PV) (40 mL/kg) daily or 1.5 X plasma volume (PV) (60 mL/kg) daily until 2 days after platelet count normalization (> 150 x 10^9) (1,2,3)
Exposure to allogenic (donor) plasma may cause serious complications such as hemolytic transfusion reactions, severe anaphylactic reaction or transfusion-related acute lung injury and may increase the risk of transfusion-transmitted disease.
Solvent/Detergent plasma such as Octaplas has similar properties as standard FFP but might decrease the risk of allergic reactions and inactivate viruses with lipid envelopes.
Use initially to achieve relatively rapid immunosuppression:
Prednisone 1 mg/kg/day if able to take PO (max dose 100 mg daily) and tapered in 30 days period.
Methylprednisolone intravenously (1 mg/Kg/day) for 3 days if unable to take PO(4)
CAPLACIZUMAB: is an antibody that targets A1 domain of von Willebrand factor and interacts with platelet glycoprotein 1b which blocks platelet-von Willebrand factor interaction and prevents the formation of microvascular thrombosis.
The USTMA suggests considering the use of Caplacizumab in the early phase of the acute event in non-bleeding patients with high clinical suspicion of iTTP (even before the results of ADAMTS-13 activity become available) or in patients with evidence of severe ADAMTS-13 deficiency and presence of inhibitor.(5-6)
RITUXIMAB: Consistent with the ISTH guidelines, the USTMA suggests considering upfront (newly diagnosed) Rituximab 375 mg/m2 weekly for 4 weeks. It is removed from the circulation by PEX therefore administration of Rituximab should be given immediately after PEX and try to avoid PEX for at least 12 hours after administration.(7)
1. Winters JL Plasma exchange: concepts, mechanisms, and an overview of the American Society for Apheresis guidelines Hematology Am Soc Hematol Educ Program (2012) 2012 (1): 7–12.
2. Sayani FA, Abrams CS. How I treat refractory thrombotic thrombocytopenic purpura. Blood. 2015 Jun 18; 125(25): 3860–3867.
3. Scully M, Goodship T. How I treat thrombotic thrombocytopenic purpura and atypical haemolytic uraemic syndrome. Br J Haematol. 2014 Mar; 164(6): 759–766.
4. Balduini CL, Gugliotta L, Luppi M, Laurenti L, Klersy C, Pieresca C, Quintini G, Iuliano F, Re R, Spedini P, Vianelli N, Zaccaria A, Pogliani EM, Musso R, Bobbio Pallavicini E, Quarta G, Galieni P, Fragasso A, Casella G, Noris P, Ascari E, Italian TTP Study Group. High versus standard dose methylprednisolone in the acute phase of idiopathic thrombotic thrombocytopenic purpura: a randomized study. Ann Hematol. 2010 Jun; 89(6):591-6
5. Peyvandi F, Scully M, Kremer Hovinga JA, et al. Caplacizumab for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2016; 374:511-522
6. Scully M, Cataland SR, Peyvandi F, et al. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019; 380:335-346
7. McDonald V, Manns K, Mackie IJ, Machin SJ, Scully MA.Rituximab pharmacokinetics during the management of acute idiopathic thrombotic thrombocytopenic purpura. J Thromb Haemost. 2010 Jun; 8(6):1201-8.