Thrombotic thrombocytopenic purpura - a disease with multiple organ manifestations. Diagnostic and therapeutic difficulties in clinical practice

Magdalena Szydełko, Joanna Szydełko, Agnieszka Szymczyk, Dominika Szymczyk, Magdalena Chomczyńska, Monika Podhorecka


Introduction: Thrombotic thrombocytopenic purpura (TTP) is a rare, heterogeneous and life-threating disease requiring prompt differential diagnosis. The most common form of that disease is idiopathic form affects usually young adults. The etiopathogenesis is most likely based on the excessive formation of platelet aggregates and microthrombosis in small vessels, capillaries due to the deficiency of a specific enzyme, ADAMTS13 (disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13).
Aim of the study: The aim of this review was to present the diagnostic difficulties of the TTP, which are mainly related to the range of multi-organ deficiency and symptoms that resemble lots of other diseases. Moreover, we discussed the current, as well as future perspectives of the treatment of thrombotic thrombocytopenic purpura.
Description of knowledge: The principal symptoms, which occur in TTP patient are caused by microangiopathic hemolytic anemia and thrombocytopenia. Moreover, that disease may also manifest by neurological, renal, cardiac abnormalities as well as abdominal disturbances, fever and flu-like symptoms. The other thrombotic microangiopathies, especially hemolytic-uremic syndrome, immune-mediated diseases, infections, stroke, myocardial infarction should be taken initially in the differential diagnosis. The current management is based on plasma exchange therapy, steroids, rituximab, but the novel methods are investigated.
Conclusions: The differential diagnosis of hematological patients presenting clinical symptoms of thrombocytopenia, anemia associated with multi-organ dysfunction, especially when we suspect an autoimmune background of a given disease is crucial to implement the appropriate therapy and save the patient's life.


thrombotic thrombocytopenic purpura; symptoms; ADAMTS13; differential diagnosis; therapy strategies

Full Text:



Tărniceriu CC, Mircea-Vicol R, Anton E, Ancuţa C, Bădulescu OV, Anton CR, et al.Thrombotic thrombocytopenic purpura: a hematological emergency. Rom J Morphol Embryol. 2014;55:1259-62.

Moschcowitz E. Hyaline thrombosis of the terminal arterioles and capillaries: hitherto undescribed disease. Proc N Y Pathol Soc 1924;24:21–4.

Rogers HJ, Allen C, Lichtin AE. Thrombotic thrombocytopenic purpura: The role of ADAMTS13. Cleve Clin J Med. 2016;83(8):597-603. doi: 10.3949/ccjm.83a.15009.

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;3(5):e237-45. doi: 10.1016/S2352-3026(16)30018-7.

Sadler JE. Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura. Blood. 2008;112(1):11-8. doi: 10.1182/blood-2008-02-078170.

Mariotte E, Veyradier A. Thrombotic thrombocytopenic purpura: from diagnosis to therapy. CurrOpin Crit Care. 2015;21(6):593-601. doi:10.1097/MCC.0000000000000255.

Saha M, McDaniel JK, Zheng XL. Thrombotic thrombocytopenic purpura: pathogenesis, diagnosis and potential novel therapeutics. J Thromb Haemost. 2017;15(10):1889-1900. doi: 10.1111/jth.13764.

Koyfman A, Brém E, Chiang VW. Thrombotic thrombocytopenic purpura. Pediatr Emerg Care. 2011;27(11):1085-8; quiz 1089-90. doi: 10.1097/PEC.0b013e318236068c.

Verbeke L, Delforge M, Dierickx D. Current insight into thrombotic thrombocytopenic purpura.Blood Coagul Fibrinolysis. 2010; 21(1):3-10. doi: 10.1097/MBC.0b013e32833335eb.

Scully M, Hunt BJ, Benjamin S, Liesner R, Rose P, PeyvandiF, et al.; British Committee for Standards in Haematology. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol. 2012;158(3):323-35. doi: 10.1111/j.1365-2141.2012.09167.x.

Peyvandi F, Palla R, Lotta LA, Mackie I, Scully MA, Machin SJ. ADAMTS-13 assays in thrombotic thrombocytopenic purpura. J Thromb Haemost. 2010;8(4):631-40. doi: 10.1111/j.1538-7836.2010.03761.x.

Yates S, Matevosyan K, Rutherford C, Shen YM, Sarode R. Bortezomib for chronic relapsing thrombotic thrombocytopenic purpura: a case report. Transfusion. 2014;54(8):2064-7. doi: 10.1111/trf.12614.

Htun KT, Davis AK. Neurological symptoms as the sole presentation of relapsed thrombotic thrombocytopenic purpura without microangiopathic haemolyticanaemia. Thromb Haemost. 2014;112(4):838-40. doi: 10.1160/TH14-04-0359.

Piton G, Navellou JC, Morati P, Patry C, Carbonnel F, Capellier G. Thrombotic thrombocytopenic purpura associated with severe acute pancreatitis in a context of decreased ADAMTS13 activity: a case report. Eur J Gastroenterol Hepatol. 2008;20(12):1226-30. doi: 10.1097/MEG.0b013e3282ffd9e6.

Abdalla H, Alfishawy M, Babigumira M, Bashir T. Malignant Hypertension and Thrombotic Thrombocytopenic Purpura: False Friends. Am J Case Rep. 2015;16:374-6. doi: 10.12659/AJCR.892787.

Zafrani L, Mariotte E, Darmon M, Canet E, Merceron S, Boutboul D, et al. Acute renal failure is prevalent in patients with thrombotic thrombocytopenic purpura associated with low plasma ADAMTS13 activity. J Thromb Haemost. 2015; 13(3):380-9. doi: 10.1111/jth.12826.

Berber I, Erkurt MA, Kuku I, Kaya E, Unlu S, Ertem K et al. Thrombotic thrombocytopenic purpura presenting with pathologic fracture: a case report. Transfus Apher Sci. 2014;51(1):73-6. doi: 10.1016/j.transci.2014.05.003.

Grall M, Azoulay E, Galicier L, Provôt F, Wynckel A, Poullin P, et al. Thrombotic thrombocytopenic purpura misdiagnosed as autoimmune cytopenia: Causes of diagnostic errors and consequence on outcome. Experience of the French thrombotic microangiopathies reference centre. Am J Hematol. 2017;92(4):381-387. doi: 10.1002/ajh.24665.

Griffin D, Al-Nouri ZL, Muthurajah D, Ross JR, Ballard RB, Terrell DR, et al. First symptoms in patients with thrombotic thrombocytopenic purpura: what are they and when do they occur? Transfusion. 2013;53(1):235-237. doi: 10.1111/j.1537-2995.2012.03934.x.

Shenkman B, Einav Y2. Thrombotic thrombocytopenic purpura and other thrombotic microangiopathic hemolytic anemias: diagnosis and classification. Autoimmun Rev. 2014; 13(4-5):584-6. doi: 10.1016/j.autrev.2014.01.004.

Unverdi S, Ceri M, Öztürk MA, Akbal E, Ensari A, Yılmaz R, et al. A patient with Crohn's disease who presented with thrombotic thrombocytopenic purpura/hemolytic uremic syndrome. Ren Fail. 2011;33(2):244-245. doi: 10.3109/0886022X.2010.541577.

George JN, Al-Nouri ZL. Diagnostic and therapeutic challenges in the thrombotic thrombocytopenic purpura and hemolytic uremic syndromes. Hematology Am Soc Hematol Educ Program. 2012; 2012:604-9. doi: 10.1182/asheducation-2012.1.604.

Kosugi N, Tsurutani Y, Isonishi A, Hori Y, Matumoto M,Fujimura Y. Influenza A infection triggers thromboticthrombocytopenic purpura by producing the anti-ADAMTS13 IgG inhibitor. Intern Med 2010;49:689-93.doi: 10.2169/internalmedicine.49.2957.

Grigioni M, Caprari P, Tarzia A, D'Avenio G.Prosthetic heart valves' mechanical loading of red blood cells in patients with hereditary membrane defects. J Biomech. 2005;38(8):1557-1565.doi: 10.1016/j.jbiomech.2004.11.020.

Alhosaini H, Jensen BC, Chang PP, Sheridan BC, Katz JN.A novel link between G6PD deficiency and hemolysis in patients with continuous-flow left ventricular assist devices.J Heart Lung Transplant. 2014;33(1):116-117. doi: 10.1016/j.healun.2013.10.028.

Boattini M, Procaccianti G. Stroke due to typical thrombotic thrombocytopenic purpura treated successfully with intravenous thrombolysis and therapeutic plasma exchange.BMJ Case Rep. 2013;2013. pii: bcr2012008426. doi: 10.1136/bcr-2012-008426.

Baron Y, Bargemann T, Harten P, Gutschmidt HJ. Thrombocytopenic thrombotic purpura: severe clinic with no CT, minor MRI, but a SPECT correlate. Eur J Radiol. 1999; 31(1):56-62.doi: 10.1016/S0720-048X(98)00088-6.

Lasek-Bal A, Kosarz-Lanczek K, Kazibutowska Z. Acute neurological symptoms of Moschcowitz disease - case report. Neurol Neurochir Pol. 2014;48(4):296-298. doi: 10.1016/j.pjnns.2014.07.002.

Fiorani L, Vianelli N, Gugliotta L, Vignatelli L, Corbelli C, D'Alessandro R. Brain MRI and SPET in thrombotic thrombocytopenic purpura. Ital J Neurol Sci. 1995; 16(3):149-151. doi: 10.1007/BF02282981

Qasim ZA, Partridge RA. Thrombotic thrombocytopenic purpura presenting as bilateral flank pain and hematuria: a case report. J Emerg Med. 2001;21(1):15-20. doi: 10.1016/S0736-4679(01)00327-4.

Torok N, Niazi M, Al Ahwel Y, Taleb M, Taji J, Assaly R. Thrombotic thrombocytopenic purpura associated with anti-glomerular basement membrane disease. Nephrol Dial Transplant. 2010;25(10):3446-3449. doi: 10.1093/ndt/gfq437.

Hawkins BM, Abu-Fadel M, Vesely SK, George JN.Clinical cardiac involvement in thrombotic thrombocytopenic purpura: a systematic review. Transfusion. 2008;48(2):382-392. doi: 10.1111/j.1537-2995.2007.01534.x.

Atreya AR, Arora S, Sivalingam SK, Giugliano GR. ST segment elevation myocardial infarction as a presenting feature of thrombotic thrombocytopenic purpura. J Cardiovasc Dis Res. 2012;3(2):167-169. doi: 10.4103/0975-3583.95377.

Tasaki T, Yamada S, Nabeshima A, Noguchi H, Nawata A, Hisaoka M, et al. An autopsy case of myocardial infarction due to idiopathic thrombotic thrombocytopenic purpura. Diagn Pathol. 2015;10:52. doi: 10.1186/s13000-015-0285-1.

Wajima T, Johnson EH. Sudden cardiac death from thrombotic thrombocytopenic purpura. Clin Appl Thromb Hemost. 2000;6(2):108-110. doi: 10.1177/ 107602960000600212.

Wahla AS, Ruiz J, Noureddine N, Upadhya B, Sane DC, Owen J. Myocardial infarction in thrombotic thrombocytopenic purpura: a single-centerexperience and literature review. Eur J Haematol. 2008;81:311–6.doi:10.1111/j.1600-0609.2008.01112.x.

Muszytowski M, Szachta A, Seifert J. Sudden cardiac death in thrombotic thrombocytopenic purpura. Kardiol Pol. 2012;70(11):1168-1169.

Wang J, Cai X, Cheng X, Song P, Jiang S, Gong J.Acute myocardial infarction caused by tumor-associated thrombotic thrombocytopenic purpura: case report. Med Princ Pract. 2014;23(3):289-291. doi: 10.1159/000354096.

Piton G, Navellou JC, Morati P, Patry C, Carbonnel F, Capellier G. Thrombotic thrombocytopenic purpura associated with severe acute pancreatitis in a context of decreased ADAMTS13 activity: a case report. Eur J Gastroenterol Hepatol. 2008;20(12):1226-1230. doi: 10.1097/MEG.0b013e3282ffd9e6.

Abeysundara PK, Athukorala I, Dalpatadu KPC, Balendran K, Dilrukshi MDSA, Fernando G. Rare Presentation of Refractory Thrombotic Thrombocytopenic Purpura: Jejunal Stricture. Int J Hematol Oncol Stem Cell Res. 2017;11(4):293-295. PMID:29340125.

Zini G, d'Onofrio G, Briggs C, Erber W, Jou JM, Lee SH, et al. ICSH recommendations for identification, diagnostic value, and quantitation of schistocytes. Int J Lab Hematol. 2012;34(2):107-116. doi: 10.1111/j.1751-553X.2011.01380.x.

Idowu M, Reddy P. Atypical thrombotic thrombocytopenic purpura in a middle-aged woman who presented with a recurrent stroke. Am J Hematol. 2013;88(3):237-239. doi: 10.1002/ajh.23249.

Ibernon M, Moreso F, Carreras L, Carrera M, Serrano T, Rama I, et al. Thrombotic thrombocytopenic purpura with severe large artery branch involvement. Nephrol Dial Transplant. 2005; 20(2):467-468. doi:10.1093/ndt/gfh596.

Barrows BD, Teruya J. Use of the ADAMTS13 activity assay improved the accuracy and efficiency of the diagnosis and treatment of suspected acquired thrombotic thrombocytopenic purpura. Arch Pathol Lab Med. 2014;138(4):546-549. doi: 10.5858/arpa.2013-0170-OA.

Shah N, Sarode R. Thrombotic thrombocytopenic purpura-what is new? J Clin Apher. 2013;28(1):30-35. doi: 10.1002/jca.21264.

Rieger M, Mannucci PM, Kremer Hovinga JA, Herzog A, Gerstenbauer G, Konetschny C, et al. ADAMTS13 autoantibodies in patients with thrombotic microangiopathies and other immunomediated diseases. Blood. 2005;106(4):1262-1267.doi: 10.1182/blood-2004-11-4490.

Yang S, Jin M, Lin S, Cataland S, Wu H. ADAMTS13 activity and antigen during therapy and follow-up of patients with idiopathic thrombotic thrombocytopenic purpura: correlation with clinical outcome. Haematologica. 2011;96(10):1521-1527. doi: 10.3324/haematol.2011.042945.

Sadler JE, Moake JL, Miyata T, George JN. Recent advances in thrombotic thrombocytopenic purpura. Hematology Am Soc Hematol Educ Program. 2004:407-23. doi: 10.1182/asheducation-2004.1.407.

Zhou A, Mehta RS, Smith RE. Outcomes of platelet transfusion in patients with thrombotic thrombocytopenic purpura: a retrospective case series study. Ann Hematol. 2015; 94(3):467-72. doi: 10.1007/s00277-014-2223-9.

Tanhehco YC, Arepally G, Metjian A. Novel therapeutic approaches for thrombotic thrombocytopenic purpura. Curr Opin Hematol. 2017; 24(6):521-8. doi: 10.1097/MOH.0000000000000375.

Cataland SR, Wu HM. Acquired thrombotic thrombocytopenic purpura: new therapeutic options and their optimal use. J Thromb Haemost. 2015; 13 Suppl 1:S223-9. doi: 10.1111/jth.12934.

Sarode R, Bandarenko N, Brecher ME, Kiss JE, Marques MB, Szczepiorkowski ZM, et al. Thrombotic thrombocytopenic purpura: 2012 American Society for Apheresis (ASFA) consensus conference on classification, diagnosis, management, and future research. J Clin Apher. 2014; 29(3):148-67. doi: 10.1002/jca.21302.

Korkmaz S, Keklik M, Sivgin S, Yildirim R, Tombak A, Kaya ME, et al. Therapeutic plasma exchange in patients with thrombotic thrombocytopenic purpura: a retrospective multicenter study. Transfus Apher Sci. 2013; 48(3):353-8. doi:10.1016/j.transci.2013.04.016.

Smycz M, Mielczarek-Palacz A, Kondera-Anasz Z, Sikora J, Machaj I, Gęsikowska K. Zastosowanie plazmaferezy w terapii oraz w preparatyce krwi. Ann. Acad. Med. Siles. 2012, 66(1):67–72.

George JN. Clinical practice. Thrombotic thrombocytopenic purpura. N Engl J Med 2006; 354:1927–1935. doi: 10.1056/NEJMcp053024.

Balduini CL, Gugliotta L, Luppi M, Laurenti L, Klersy C, Pieresca C, et al. High versus standard dose methylprednisolone in the acute phase of idiopathic thrombotic thrombocytopenic purpura: a randomized study. Ann Hematol. 2010; 89(6):591-596. doi: 10.1007/s00277-009-0877-5.

Bell WR, Braine HG, Ness PM, Kickler TS. Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Clinical experience in 108 patients. N Engl J Med. 199; 325(6):398-403. doi: 10.1056/NEJM199108083250605.

Westwood JP, Webster H, McGuckin S, McDonald V, Machin SJ, Scully M. Rituximab for thrombotic thrombocytopenic purpura: benefit of early administration during acute episodes and use of prophylaxis to prevent relapse. J Thromb Haemost. 2013; 11(3):481-490. doi: 10.1111/jth.12114.

Wieland I, Kentouche K, Jentzsch M, Lothschütz D, Graf N, Sykora KW. Long-term remission of recurrent thrombotic thrombocytopenic purpura (TTP) after Rituximab in children and young adults. Pediatr Blood Cancer. 2015; 62(5):823-829. doi: 10.1002/pbc.25398.

Kirui N, Sokwala A. A case of refractory thrombotic thrombocytopenic purpura treated with plasmapheresis and rituximab. S Afr Med J. 2016; 106(7):689-691. doi: 10.7196/SAMJ.2016.v106i7.9856.

Hie M, Gay J, Galicier L, Provôt F, Presne C, Poullin P, et al. Preemptive rituximab infusions after remission efficiently prevent relapses in acquired thrombotic thrombocytopenic purpura: Experience of the French thrombotic microangiopathies reference center. Blood 2014; 124(2):204–210. doi: 10.1182/blood-2014-01-550244.

Goyal J, Adamski J, Lima JL, Marques MB. Relapses of thrombotic thrombocytopenic purpura after treatment with rituximab. J Clin Apher. 2013; 28(6):390-394. doi: 10.1002/jca.21289.

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; 40(1):104-111. doi: 10.1097/CCM.0b013e31822e9d66.

Pequeño-Luévano M, Villarreal-Martínez L, Jaime-Pérez JC, Gómez-de-León A, Cantú-Rodríguez OG, González-Llano O, et al. Low-dose rituximab for the treatment of acute thrombotic thrombocytopenic purpura: report of four cases. Hematology. 2013; 18(4):233-236. doi: 10.1179/1607845412Y.0000000073.

Vazquez-Mellado A, Pequeño-Luévano M, Cantu-Rodriguez OG, Villarreal-Martínez L, Jaime-Pérez JC, Gomez-De-Leon A, et al. More about low-dose rituximab and plasma exchange as front-line therapy for patients with thrombotic thrombocytopenic purpura. Hematology. 2016; 21(5):311-316. doi: 10.1080/10245332.2015.1133008.

Benhamou Y, Paintaud G, Azoulay E, Poullin P, Galicier L, Desvignes C, et al. Efficacy of a rituximab regimen based on B cell depletion in thrombotic thrombocytopenic purpura with suboptimal response to standard treatment: Results of a phase II, multicenter noncomparative study. Am J Hematol. 2016; 91(12):1246-1251. doi: 10.1002/ajh.24559.

Abu-Hishmeh M, Sattar A, Zarlasht F, Ramadan M, Abdel-Rahman A, Hinson S, et al. Systemic Lupus Erythematosus Presenting as Refractory Thrombotic Thrombocytopenic Purpura: A Diagnostic and Management Challenge. A Case Report and Concise Review of the Literature. Am J Case Rep. 2016;17:782-787.doi: 10.12659/AJCR.898955.



  • There are currently no refbacks.

Copyright (c) 2018 © The Author(s)

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Journal of Education, Health and Sport formerly Journal of Health Sciences

Declaration on the original version.

Editors indicates that the main version of the magazine is to issue a "electronic".

The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019.

1223 Journal of Education, Health and Sport eISSN 2391-8306 7

ISSN 2391-8306 formerly ISSN: 1429-9623 / 2300-665X

Archives 2011 - 2014

PBN 2011 - 2014

POL-index 2011 - 2014

BASE 2011 - 2014

Indexed in Bases, Bazy indeksacyjne: ERIH Plus, Worldcat, PBN/POL-Index, ICI Journals Master List, Directory of Open Access Journals (DOAJ), ZBD, Ulrich's periodicals, Google Scholar, Polska Bibliografia Lekarska

US NLM = 101679844

101679844 - NLM Catalog Result - NCBI

Find a library that holds this journal:

Journal Language(s): English 

PBN Poland



Redaction, Publisher and Editorial Office

Instytut Kultury Fizycznej Uniwersytet Kazimierza Wielkiego w Bydgoszczy, Institute of Physical Education Kazimierz Wielki University in Bydgoszcz, Poland 85-091 Bydgoszcz ul. Sportowa 2 Copyright by Instytut Kultury Fizycznej UKW w Bydgoszczy  Open Access ISSN 2391-8306 formerly ISSN: 1429-9623 / 2300-665X

The journal has been approved for inclusion in ERIH PLUS.

The ERIH PLUS listing of the journal is available at

SIC Science citation index (calculated on the basis of TCI and Page Rank) 0

Russian Impact factor 0.16

Indexed in Index Copernicus Journals Master List.,p24782242,3.html

ICV 2018 = 95.95 ICV 2017 = 91.30 ICV 2016 = 84.69 ICV 2015 = 93.34 ICV 2014 = 89.51 Standardized Value: 8.27 ICV 2013: 7.32 ICV 2012: 6.41 ICV 20115.48

The InfoBase Index IBI Factor for the year 2015 is 3.56 in InfoBase


Universal Impact Factor 1.78 for year 2012. (

Indexed in Polish Scholarly Bibliography (PBN) (PBN Polska Bibliografia Naukowa) (

is a portal of the Polish Ministry of Science and Higher Education, collecting information on publications of Polish scientists and on Polish and foreign scholarly journals. Polish Scholarly Bibliograhpy is a part of POL-on - System of Information on Higher Education. It is operated by the Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw.

Indexed in Russian Sciences Index Российский индекс научного цитирования (РИНЦ)

Indexed in Arianta Polish scientific and professional electronic journals Aneta Drabek i Arkadiusz Pulikowski