Diagnostic Considerations

To make an accurate diagnosis, the clinician must recognize the similarity between thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS). In addition to HUS, the differential diagnosis also includes immune thrombocytopenic purpura (ITP) and disseminated intravascular coagulation (DIC), two entities with very different modes of therapy (see the image below).

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

Additional diagnoses that should be considered in patients presenting with an acute thrombotic microangiopathy (TMA), especially in those in whom levels of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity are nondeficient (> 10%) include the following^[20]:

Drug-induced TMA
Cancer-associated TMA
Hematopoietic transplant–associated TMA

Differential Diagnoses

Workup

Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood. 2017 May 25. 129 (21):2836-2846. [QxMD MEDLINE Link].
Stanley M, Killeen RB, Michalski JM. Thrombotic Thrombocytopenic Purpura. 2023 Jan. [QxMD MEDLINE Link]. [Full Text].
Tsai HM. Thrombotic thrombocytopenic purpura and the atypical hemolytic uremic syndrome: an update. Hematol Oncol Clin North Am. 2013 Jun. 27(3):565-84. [QxMD MEDLINE Link].
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].
Mariotte E, Azoulay E, Galicier L, Rondeau E, Zouiti F, Boisseau P, et al. Epidemiology and pathophysiology of adulthood-onset thrombotic microangiopathy with severe ADAMTS13 deficiency (thrombotic thrombocytopenic purpura): a cross-sectional analysis of the French national registry for thrombotic microangiopathy. Lancet Haematol. 2016 May. 3 (5):e237-45. [QxMD MEDLINE Link].
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.
Sukumar S, Lämmle B, Cataland SR. Thrombotic Thrombocytopenic Purpura: Pathophysiology, Diagnosis, and Management. J Clin Med. 2021 Feb 2. 10 (3):[QxMD MEDLINE Link]. [Full Text].
Vesely SK, George JN, Lammle B, et al. ADAMTS13 activity in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: relation to presenting features and clinical outcomes in a prospective cohort of 142 patients. Blood. 2003 Jul 1. 102(1):60-8. [QxMD MEDLINE Link].
[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].
Markham-Lee Z, Morgan NV, Emsley J. Inherited ADAMTS13 mutations associated with Thrombotic Thrombocytopenic Purpura: a short review and update. Platelets. 2023 Dec. 34 (1):2138306. [QxMD MEDLINE Link].
Lammle B. A third form of thrombotic thrombocytopenic purpura?. Haematologica. 2023 Feb 1. 108 (2):299-300. [QxMD MEDLINE Link]. [Full Text].
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].
Jhaveri KD, Scheuer A, Cohen J, Gordon B. Treatment of refractory thrombotic thrombocytopenic purpura using multimodality therapy including splenectomy and cyclosporine. Transfus Apher Sci. 2009 Aug. 41(1):19-22. [QxMD MEDLINE Link].
Scully M, McDonald V, Cavenagh J, et al. A phase 2 study of the safety and efficacy of rituximab with plasma exchange in acute acquired thrombotic thrombocytopenic purpura. Blood. 2011 Aug 18. 118(7):1746-53. [QxMD MEDLINE Link].
Akwaa F, Antun A, Cataland SR. How I treat immune-mediated thrombotic thrombocytopenic purpura after hospital discharge. Blood. 2022 Aug 4. 140 (5):438-444. [QxMD MEDLINE Link].
Comparon C, Galicier L, Rebibou JM, Coppo P, Benhamou Y. Preemptive cyclosporin A in immune-mediated thrombotic thrombocytopenic purpura. Eur J Haematol. 2023 Feb. 110 (2):157-160. [QxMD MEDLINE Link]. [Full Text].
Beranger N, Benghezal S, Joly BS, Capdenat S, Delton A, Stepanian A, et al. Diagnosis and follow-up of thrombotic thrombocytopenic purpura with an automated chemiluminescent ADAMTS13 activity immunoassay. Res Pract Thromb Haemost. 2021 Jan. 5 (1):81-93. [QxMD MEDLINE Link]. [Full Text].
Staley EM, Cao W, Pham HP, Kim CH, Kocher NK, Zheng L, et al. Clinical factors and biomarkers predicting outcome in patients with immune-mediated thrombotic thrombocytopenic purpura. Haematologica. 2018 Aug 31. [QxMD MEDLINE Link]. [Full Text].
Shumak KH, Rock GA, Nair RC. Late relapses in patients successfully treated for thrombotic thrombocytopenic purpura. Canadian Apheresis Group. Ann Intern Med. 1995 Apr 15. 122(8):569-72. [QxMD MEDLINE Link].
Roriz M, Landais M, Desprez J, et al; French Thrombotic Microangiopathies Reference Center. Risk Factors for Autoimmune Diseases Development After Thrombotic Thrombocytopenic Purpura. Medicine (Baltimore). 2015 Oct. 94 (42):e1598. [QxMD MEDLINE Link]. [Full Text].
Sikka P, Chopra S, Aggarwal N, Suri V, Chandrasekaran A. Thrombotic thrombocytopenic purpura in the first trimester of pregnancy. Asian J Transfus Sci. 2013 Jan. 7(1):79-80. [QxMD MEDLINE Link]. [Full Text].

Media Gallery

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

of 1

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.