Thrombotisch-thrombozytopenische Purpura (TTP)
Zuletzt bearbeitet: Zuletzt revidiert:
Zuletzt revidiert von:Kristin Haavisto
Definition:
Thrombotische Mikroangiopathie mit mikroangiopathischer hämolytischer Anämie, Thrombozytopenie und disseminierten mikrovaskulären Thromben. Zugrunde liegender Pathomechanismus ist ein Mangel an ADAMTS13, einer Protease, die spezifisch für die Spaltung des Von-Willebrand-Faktors zuständig ist.
Häufigkeit:
Sehr selten, jährliche Inzidenz in Deutschland ca. 1,5/1.000.000.
Symptome:
Häufig unspezifisch. Abgeschlagenheit, Luftnot, neurologische Symptome, Ischämiezeichen, Nierenversagen, Hauteinblutungen, Petechien.
Diagnostik:
Hämolyse-Parameter (erhöhte LDH, nicht nachweisbares Haptoglobin, erhöhte Retikulozytenzahl), Schistozyten im Blutausstrich, deutlich verringerte ADAMTS13-Aktivität (< 10 %).
Therapie:
Sofortige Einleitung einer Plasmapherese, Gabe von Fresh Frozen Plasma (FFP) und Kortikosteroiden. Erweiterung der Therapie durch Hinzunahme von Rituximab und Caplacizumab.
Prognose:
Unbehandelt liegt die Letalität bei > 90 %, unter Therapie bei ca. 5–10 %.
- Sukumar S, Lämmle B, Cataland SR. Thrombotic Thrombocytopenic Purpura: Pathophysiology, Diagnosis, and Management. J Clin Med. 2021 Feb 2;10(3):536. pubmed.ncbi.nlm.nih.gov
- Tsai HM, Lian EC. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med. 1998 Nov 26;339(22):1585-94. pubmed.ncbi.nlm.nih.gov
- Furlan M, Robles R, Galbusera M, et al. von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N Engl J Med. 1998 Nov 26;339(22):1578-84. doi: 10.1056/NEJM199811263392202. PMID: 9828245. pubmed.ncbi.nlm.nih.gov
- Veyradier A, Meyer D. Thrombotic thrombocytopenic purpura and its diagnosis. J Thromb Haemost 2005; 3: 2420-7. PubMed
- Scully M, Hunt BJ, Benjamin S, 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. pmid:22624596 PubMed
- Moake JL, Rudy CK, Troll JH, et al. Unusually large plasma factor VIII:von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura. N Engl J Med. 1982 Dec 2;307(23):1432-5. pubmed.ncbi.nlm.nih.gov
- Furlan M, Robles R, Lämmle B. Partial purification and characterization of a protease from human plasma cleaving von Willebrand factor to fragments produced by in vivo proteolysis. Blood. 1996 May 15;87(10):4223-34. pubmed.ncbi.nlm.nih.gov
- Tsai HM. Physiologic cleavage of von Willebrand factor by a plasma protease is dependent on its conformation and requires calcium ion. Blood. 1996 May 15;87(10):4235-44. pubmed.ncbi.nlm.nih.gov
- Furlan M, Robles R, Galbusera M, et al. von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N Engl J Med. 1998 Nov 26;339(22):1578-84. pubmed.ncbi.nlm.nih.gov
- Miesbach W, Menne J, Bommer M, et al. Incidence of acquired thrombotic thrombocytopenic purpura in Germany: a hospital level study. Orphanet J Rare Dis. 2019 Nov 15;14(1):260. www.ncbi.nlm.nih.gov
- Sadler JE. What's new in the diagnosis and pathophysiology of thrombotic thrombocytopenic purpura. Hematology Am Soc Hematol Educ Program. 2015;2015(1):631-6. www.ncbi.nlm.nih.gov
- Martino S, Jamme M, Deligny C, et al.; French Reference Center for Thrombotic Microangiopathies. Thrombotic Thrombocytopenic Purpura in Black People: Impact of Ethnicity on Survival and Genetic Risk Factors. PLoS One. 2016 Jul 6;11(7) www.ncbi.nlm.nih.gov
- Tarr PI, Gordon CA, Chandler WL. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet 2005; 365: 1073-86. PubMed
- Jokiranta TS. HUS and atypical HUS. Blood. 2017 May 25;129(21):2847-2856. pubmed.ncbi.nlm.nih.gov
- Blombery P, Scully M. Management of thrombotic thrombocytopenic purpura: current perspectives. J Blood Med 2014 Feb 5; 5: 15-23. pmid:24523598 PubMed
- Lemiale V, Valade S, Mariotte E. Unresponsive Thrombotic Thrombocytopenic Purpura (TTP): Challenges and Solutions. Ther Clin Risk Manag. 2021 Jun 3;17:577-587. www.ncbi.nlm.nih.gov
- Lämmle B, Kremer Hovinga JA, Alberio L. Thrombotic thrombocytopenic purpura. J Thromb Haemost. 2005 Aug;3(8):1663-75. pubmed.ncbi.nlm.nih.gov
- Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020 Oct;18(10):2496-2502. pubmed.ncbi.nlm.nih.gov
- Matsumoto M, Fujimura Y, Wada H, et al.; For TTP group of Blood Coagulation Abnormalities Research Team, Research on Rare and Intractable Disease supported by Health, Labour, and Welfare Sciences Research Grants. Diagnostic and treatment guidelines for thrombotic thrombocytopenic purpura (TTP) 2017 in Japan. Int J Hematol. 2017 Jul;106(1):3-15. pubmed.ncbi.nlm.nih.gov
- Hie M, Gay J, Galicier L, et al. Preemptive rituximab infusions after remission efficiently prevent relapses in acquired thrombotic thrombocytopenic purpura. Blood. 2014 Jul 10;124(2):204-10. pubmed.ncbi.nlm.nih.gov
- Page EE, Kremer Hovinga JA, Terrell DR, Vesely SK, George JN. Thrombotic thrombocytopenic purpura: diagnostic criteria, clinical features, and long-term outcomes from 1995 through 2015. Blood Adv. 2017 Apr 6;1(10):590-600. pubmed.ncbi.nlm.nih.gov
- Scully, M., Cohen, H., Cavenagh, J. et al. Remission in acute refractory and relapsing thrombotic thrombocytopenic purpura following rituximab is associated with a reduction in IgG antibodies to ADAMTS-13. Haematol 2007 Feb; 136(3): 451-61. pmid:17233847 PubMed
- Coppo P, Bubenheim M, Azoulay E, et al. A regimen with caplacizumab, immunosuppression, and plasma exchange prevents unfavorable outcomes in immune-mediated TTP. Blood. 2021 Feb 11;137(6):733-742. pubmed.ncbi.nlm.nih.gov
- Scully M, Cataland SR, Peyvandi F, et al. Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura. N Engl J Med. 2019 Jan 24;380(4):335-346 pubmed.ncbi.nlm.nih.gov
- Roose E, Joly BS. Current and Future Perspectives on ADAMTS13 and Thrombotic Thrombocytopenic Purpura. Hamostaseologie. 2020 Aug;40(3):322-336. pubmed.ncbi.nlm.nih.gov
- Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood 2017 May 25; 129(21): 2836-2846. pmid:28416507 PubMed
- Saha M, McDaniel JK, Zheng XL. Thrombotic thrombocytopenic purpura: pathogenesis, diagnosis and potential novel therapeutics. J Thromb Haemost. 2017 Oct;15(10):1889-1900. www.ncbi.nlm.nih.gov
- Kremer Hovinga JA, Vesely SK, Terrell DR, et al. Survival and relapse in patients with thrombotic thrombocytopenic purpura. Blood. 2010 Feb 25;115(8):1500-11; quiz 1662. doi: 10.1182/blood-2009-09-243790. Epub 2009 Dec 23. PMID: 20032506. pubmed.ncbi.nlm.nih.gov
- Kristin Haavisto, Dr. med., Fachärztin für Innere Medizin und Hämato-/Onkologie, Münster
Frühere Autor*innen
- Die ursprüngliche Version dieses Artikels basiert auf einem entsprechenden Artikel im norwegischen hausärztlichen Online-Handbuch Norsk Elektronisk Legehåndbok(NEL, https://legehandboka.no/).