Sections

Thrombotic Thrombocytopenic Purpura (TTP)

Sections Thrombotic Thrombocytopenic Purpura (TTP)
Overview
Presentation
- History
- Physical
- Causes
- Show All
DDx
Workup
Treatment
Guidelines
Medication
Follow-up
Questions & Answers
References

Medication

Medication Summary

The therapy of choice is plasma exchange with fresh frozen plasma and immunosuppression.

The US Food and Drug Administration (FDA) has 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.^[7]

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.^[37]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.^[38]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.^[29]

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.^[23]

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.^[7]

Caplacizumab (Cablivi, caplacizumab-yhdp)

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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)

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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.

Class Summary

Plasma exchange with FFP is the therapy of choice for TTP.Fresh frozen plasma (FFP, Octaplas)

Fresh frozen plasma (FFP, Octaplas)

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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.

Class Summary

These agents are used as an adjunct to plasma exchange.

Vincristine (Oncovin, Vincasar)

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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.

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)

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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.

Follow-up

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Schofield J, Hosseinzadeh S, Burton K, Pavord S, Dutt T, Doree C, et al. Drug-induced thrombotic thrombocytopenic purpura: A systematic review and review of European and North American pharmacovigilance data. Br J Haematol. 2023 May. 201 (4):766-773. [QxMD MEDLINE Link].
Ferrari S, Mudde GC, Rieger M, Veyradier A, Kremer Hovinga JA, Scheiflinger F. IgG-subclass distribution of anti-ADAMTS13 antibodies in patients with acquired thrombotic thrombocytopenic purpura. J Thromb Haemost. 2009 Aug 11. [QxMD MEDLINE Link].
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Scully M, Cataland SR, Peyvandi F, Coppo P, Knöbl P, Kremer Hovinga JA, et al. Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura. N Engl J Med. 2019 Jan 24. 380 (4):335-346. [QxMD MEDLINE Link].
Lowes R. FDA Okays Blood Plasma Product for Clotting Disorders. Medscape Medical News. January 17, 2013. Available at http://www.medscape.com/viewarticle/777822. Accessed: February 8, 2019.
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[Guideline] Zheng XL, Vesely SK, Cataland SR, Coppo P, Geldziler B, Iorio A, et al. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020 Oct. 18 (10):2496-2502. [QxMD MEDLINE Link]. [Full Text].
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Joly BS, Roose E, Coppo P, Vanhoorelbeke K, Veyradier A. ADAMTS13 conformation is closed in non-immune acquired thrombotic thrombocytopenic purpura of unidentified pathophysiology. Haematologica. 2023 Feb 1. 108 (2):638-644. [QxMD MEDLINE Link]. [Full Text].
Cauchois R, Muller R, Lagarde M, Dignat-George F, Tellier E, Kaplanski G. Is Endothelial Activation a Critical Event in Thrombotic Thrombocytopenic Purpura?. J Clin Med. 2023 Jan 18. 12 (3):[QxMD MEDLINE Link]. [Full Text].
Sauna ZE, Okunji C, Hunt RC, et al. Characterization of conformation-sensitive antibodies to ADAMTS13, the von Willebrand cleavage protease. PLoS One. 2009 Aug 5. 4(8):e6506. [QxMD MEDLINE Link]. [Full Text].
Miller DP, Kaye JA, Shea K, Ziyadeh N, Cali C, Black C, et al. Incidence of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome. Epidemiology. 2004 Mar. 15 (2):208-15. [QxMD MEDLINE Link].
Scully M, Thomas M, Underwood M, Watson H, Langley K, Camilleri RS, et al. Thrombotic thrombocytopenic purpura and pregnancy: presentation, management, and subsequent pregnancy outcomes. Blood. 2014 Jul 10. 124(2):211-9. [QxMD MEDLINE Link].
Bouw MC, Dors N, van Ommen H, Ramakers-van Woerden NL. Thrombotic thrombocytopenic purpura in childhood. Pediatr Blood Cancer. 2009 Jun 18. 53(4):537-542. [QxMD MEDLINE Link].
Masias C, Vasu S, Cataland SR. None of the above: thrombotic microangiopathy beyond TTP and HUS. Blood. 2017 May 25. 129 (21):2857-2863. [QxMD MEDLINE Link].
Wu N, Liu J, Yang S, Kellett ET, Cataland SR, Li H, et al. Diagnostic and prognostic values of ADAMTS13 activity measured during daily plasma exchange therapy in patients with acquired thrombotic thrombocytopenic purpura. Transfusion. 2014 Jun 23. [QxMD MEDLINE Link].
Coppo P, Veyradier A. Current management and therapeutical perspectives in thrombotic thrombocytopenic purpura. Presse Med. 2012 Mar. 41(3 Pt 2):e163-76. [QxMD MEDLINE Link].
[Guideline] Scully M, Hunt BJ, Benjamin S, Liesner R, Rose P, Peyvandi F, et al. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol. 2012 Aug. 158 (3):323-35. [QxMD MEDLINE Link]. [Full Text].
Shah N, Rutherford C, Matevosyan K, Shen YM, Sarode R. Role of ADAMTS13 in the management of thrombotic microangiopathies including thrombotic thrombocytopenic purpura (TTP). Br J Haematol. 2013 Nov. 163 (4):514-9. [QxMD MEDLINE Link].
Connell NT, Cheves T, Sweeney JD. Effect of ADAMTS13 activity turnaround time on plasma utilization for suspected thrombotic thrombocytopenic purpura. Transfusion. 2015 Oct 12. [QxMD MEDLINE Link].
Duffy SM, Coyle TE. Platelet transfusions and bleeding complications associated with plasma exchange catheter placement in patients with presumed thrombotic thrombocytopenic purpura. J Clin Apher. 2013 May 30. [QxMD MEDLINE Link].
Marn Pernat A, Buturovic-Ponikvar J, Kovac J, et al. Membrane plasma exchange for the treatment of thrombotic thrombocytopenic purpura. Ther Apher Dial. 2009 Aug. 13(4):318-21. [QxMD MEDLINE Link].
Michael M, Elliott EJ, Craig JC, Ridley G, Hodson EM. Interventions for hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: a systematic review of randomized controlled trials. Am J Kidney Dis. 2009 Feb. 53(2):259-72. [QxMD MEDLINE Link].
Froissart A, Buffet M, Veyradier A, Poullin P, Provôt F, Malot S, et al. Efficacy and safety of first-line rituximab in severe, acquired thrombotic thrombocytopenic purpura with a suboptimal response to plasma exchange. Experience of the French Thrombotic Microangiopathies Reference Center. Crit Care Med. 2012 Jan. 40(1):104-11. [QxMD MEDLINE Link].
Becerra E, Scully MA, Leandro MJ, Heelas EO, Westwood JP, De La Torre I, et al. Effect of rituximab on B-cell phenotype and serum B-cell activating factor levels in patients with Thrombotic Thrombocytopenic Purpura. Clin Exp Immunol. 2014 Oct 22. [QxMD MEDLINE Link].
Coppo P, French Reference Center for Thrombotic Microangiopathies. Treatment of autoimmune thrombotic thrombocytopenic purpura in the more severe forms. Transfus Apher Sci. 2017 Feb. 56 (1):52-56. [QxMD MEDLINE Link].
Jestin M, Benhamou Y, Schelpe AS, et al. Preemptive rituximab prevents long-term relapses in immune-mediated thrombotic thrombocytopenic purpura. Blood. 2018 Sep 10. [QxMD MEDLINE Link].
Patriquin CJ, Thomas MR, Dutt T, McGuckin S, Blombery PA, Cranfield T, et al. Bortezomib in the treatment of refractory thrombotic thrombocytopenic purpura. Br J Haematol. 2016 Mar 24. [QxMD MEDLINE Link].
van den Berg J, Kremer Hovinga JA, Pfleger C, Hegemann I, Stehle G, Holbro A, et al. Daratumumab for immune thrombotic thrombocytopenic purpura. Blood Adv. 2022 Feb 8. 6 (3):993-997. [QxMD MEDLINE Link]. [Full Text].
Zhou A, Mehta RS, Smith RE. Outcomes of platelet transfusion in patients with thrombotic thrombocytopenic purpura: a retrospective case series study. Ann Hematol. 2014 Oct 7. [QxMD MEDLINE Link].
Gringauz I, Carmel-Neiderman NN, Mangel T, Portnoy O, Segal G, Goren I. Marked Improvement in Refractory TTP Directly after H. pylori Eradication Therapy. Case Rep Hematol. 2016. 2016:1568586. [QxMD MEDLINE Link]. [Full Text].
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Media Gallery

Differential diagnosis of immune thrombocytopenia (ITP), thrombotic thrombocytopenic purpura (TTP), and disseminated intravascular coagulation (DIC).

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Author

Theodore Wun, MD, FACP Professor of Medicine, Professor of Pathology and Laboratory Medicine, University of California Davis School of Medicine; Chief of Hematology/Oncology, Program Director, Veterans Affairs Northern California Health Care System; Medical Director, University of California Davis CCRC

Theodore Wun, MD, FACP is a member of the following medical societies: American Association of Blood Banks, American Society for Blood and Marrow Transplantation, American College of Physicians, American Federation for Medical Research, American Society of Hematology, SWOG

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Marcel E Conrad, MD Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, The Society of Federal Health Professionals (AMSUS), International Society of Hematology, Society for Experimental Biology and Medicine, SWOG

Disclosure: Partner received none from No financial interests for none.

Chief Editor

Srikanth Nagalla, MD, MS, FACP Chief of Benign Hematology, Miami Cancer Institute, Baptist Health South Florida; Clinical Professor of Medicine, Florida International University, Herbert Wertheim College of Medicine

Srikanth Nagalla, MD, MS, FACP is a member of the following medical societies: American Society of Hematology, Association of Specialty Professors

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Alexion; Alnylam; Kedrion; Sanofi; Dova; Apellis; Pharmacosmos<br/>Serve(d) as a speaker or a member of a speakers bureau for: Sobi; Sanofi; Rigel.

Acknowledgements

Wadie F Bahou, MD Chief, Division of Hematology, Hematology/Oncology Fellowship Director, Professor, Department of Internal Medicine, State University of New York at Stony Brook

Wadie F Bahou, MD is a member of the following medical societies: American Society of Hematology

Disclosure: Nothing to disclose.

Sections Thrombotic Thrombocytopenic Purpura (TTP)
Overview
Presentation
- History
- Physical
- Causes
- Show All
DDx
Workup
Treatment
Guidelines
Medication
Follow-up
Questions & Answers
References

Thrombotic Thrombocytopenic Purpura (TTP) Medication

Medication Summary

Monoclonal antibody

Class Summary

Caplacizumab (Cablivi, caplacizumab-yhdp)