Zakrzepowa plamica małopłytkowa – diagnostyka i leczenie

• Authors: Jolanta Korsak

Title variants

EN

Thrombotic thrombocytopenic purpura – diagnosis and treatment

• Languages of publication: PL

Abstracts

PL

Zakrzepowa plamica małopłytkowa (thrombotic thrombocytopenic purpura, TTP) początkowo charakteryzowała się pentadą objawów: małopłytkowością, niedokrwistością hemolityczną mikroangiopatyczną, zaburzeniami układu nerwowego, niewydolnością nerek i gorączką. Jednak u 35% chorych z rozpoznaniem TTP nie stwierdza się wszystkich tych dolegliwości: nie występują u nich objawy neurologiczne, zaburzenia funkcji nerek oraz gorączka. Obecnie zakrzepową plamicę małopłytkową rozpoznaje się na podstawie małopłytkowości i niedokrwistości mikroangiopatycznej. Diagnostyka obejmuje badanie morfologiczne krwi obwodowej wraz z rozmazem, badanie czynności nerek i oznaczenie aktywności LDH. Pomocne w rozpoznaniu jest oznaczenie aktywności metaloproteazy ADAMTS13 i miana przeciwciał anty-ADAMTS13. W terapii w pierwszym rzucie stosuje się plazmaferezę leczniczą – powinna ona zostać przeprowadzona nawet wtedy, gdy diagnoza jest niepewna. Plazmafereza usuwa multimery ULvWF i nabyte przeciwciała skierowane przeciw ADAMTS13. Przetoczenie osocza nie jest tak efektywne jak plazmafereza, lecz może być stosowane tymczasowo. Efekt leczenia oceniany jest na podstawie unormowania się aktywności LDH oraz ustąpienia małopłytkowości, niedokrwistości i zmian neurologicznych. Inną możliwością terapeutyczną jest podawanie glikokortykosteroidów oraz immunoglobulin. U niektórych chorych korzystne może być wykonanie splenektomii. Ostatnio stosuje się także rytuksymab – powoduje on redukcję miana inhibitora ADAMTS13 i wzrost aktywności enzymu. Po leczeniu rytuksymabem odnotowano remisje kliniczne w przypadkach, w których zawiodły inne metody terapii.

EN

Thrombotic thrombocytopenic purpura (TTP) was once diagnosed with five manifestation: thrombocytopenia, microangiopathic haemolytic anaemia, nervous system malfunctioning, renal failure and fever. Yet 35% of patients in whom TTP is diagnosed do not develop all manifestations, i.e. neurologic manifestations, renal dysfunction and fever. At present the basis for TTP diagnosis is thrombocytopenia and microangiopathic haemolytic anaemia (MAHA). The diagnosis includes blood count, blood film, renal function, LDH level. A helpful parameter in diagnosing TTP is ADAMTS13 metalloproteinase and anti-ADAMTS13 antibodies. The treatment starts with therapeutic plasmapheresis. Plasmapheresis should be undertaken even when the diagnosis is not confirmed. It removes ULvWF multimers and acquired anti-ADAMTS13. Plasma transfusion is not as effective as plasmapheresis but it can be used provisionally. The effectiveness of the treatment is assessed by lack of thrombocytopenia normal LDH level, lack of anaemia and neurological disorders. Another therapeutic option is to use glicocorticosteroids and immunoglobulins. In some patients a beneficial procedure may be splenectomy. TTP therapy has recently employed rituximab. It reduces ADAMTS13 inhibitor ratio and increases proteinase activity. Rituximab treatment is reported to have resulted in clinical remissions in the cases where other treatment modalities failed.

Keywords

EN

ADAMTS13; haemolytic uremic syndrome; plasmapheresis; plazmafereza; thrombotic thrombocytopenia purpura; zakrzepowa plamica małopłytkowa; zespół hemolityczno-mocznicowy

Discipline

• MEDICINE: MEDICINE

• Publisher: Medical Communications
• Journal: Pediatria i Medycyna Rodzinna
• Year: 2013
• Volume: 9
• Issue: 4
• Pages: 323-330

Contributors

author

Jolanta Korsak

• Zakład Transfuzjologii Klinicznej, Wojskowy Instytut Medyczny, Warszawa. Kierownik Zakładu: dr hab. n. med. Jolanta Korsak, prof. nadzw. WIM

References

• 1. Moake J.: Thrombotic thrombocytopenia purpura (TTP) and other thrombotic microangiopathies. Best Pract. Res. Clin. Haematol. 2009; 22: 567–576.
• 2. Hoffman R., Benz E.J., Shattil S.J. i wsp. (red.): Haematology: Basic Principles and Practice. Elsevier, Philadelphia 2013: 1925–1939.
• 3. Miller D.P., Kaye J.A., Shea K. i wsp.: Incidence of thrombotic thrombocytopenic purpura/haemolytic uremic syndrome. Epidemiology 2004; 15: 208–215.
• 4. Terrell D.R., Williams L.A., Vesely S.K. i wsp.: The incidence of thrombotic thrombocytopenic purpura-haemolytic uremic syndrome: all patients, idiopathic patients, and patients with severe ADAMTS-13 deficiency. J. Thromb. Haemost. 2005; 3: 1432–1436.
• 5. Fujikawa K., Suzuki H., McMullen B., Chung D.: Purification of human von Willebrand factor-cleaving protease and its identification as a new member of the metalloproteinase family. Blood 2001; 98: 1662–1666.
• 6. Levy G.G., Nichols W.C., Lian E.C. i wsp.: Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature 2001; 413: 488–494.
• 7. Zheng X.L., Sadler J.E.: Pathogenesis of thrombotic microangiopathies. Annu. Rev. Pathol. 2008; 3: 249–277.
• 8. Peyvandi F., Ferrari S., Lavoretano S. i wsp.: Von Willebrand factor cleaving protease (ADAMTS-13) and ADAMTS-13 neutralizing autoantibodies in 100 patients with thrombotic thrombocytopenic purpura. Br. J. Haematol. 2004; 127: 433–439.
• 9. George J.N., Li X., McMinn J.R. i wsp.: Thrombotic thrombocytopenic purpura-haemolytic uremic syndrome following allogeneic HPC transplantation: a diagnostic dilemma. Transfusion 2004; 44: 294–304.
• 10. Fontana S., Gerritsen H.E., Kremer Hovinga J. i wsp.: Microangiopathic haemolytic anaemia in metastasizing malignant tumours is not associated with a severe deficiency of the von Willebrand factor-cleaving protease. Br. J. Haematol. 2001; 113: 100–102.
• 11. Galbusera M., Noris M., Remuzzi G.: Thrombotic thrombocytopenic purpura – then and now. Semin. Thromb. Hemost. 2006; 32: 81–89.
• 12. Kwaan H.C., Gordon L.I.: Thrombotic microangiopathy in the cancer patient. Acta Hematol. 2001; 106: 52–56.
• 13. Werner T.L., Agarwal N., Carney H.M., Rodgers G.M.: Management of cancer-associated thrombotic microangiopathy: what is the right approach? Am. J. Hematol. 2007; 82: 295–298.
• 14. Zakarija A., Kwaan H.C., Moake J.L. i wsp.: Ticlopidine- and clopidogrel-associated thrombotic thrombocytopenic purpura (TTP): review of clinical, laboratory, epidemiological, and pharmacovigilance findings (1989–2008). Kidney Int. Suppl. 2009; 112: 20–24.
• 15. Scully M., Hunt B.J., Benjamin S. i wsp.: Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br. J. Haematol. 2012; 158: 323–335.
• 16. Scully M., Yarranton H., Liesner R. i wsp.: Regional UK TTP registry: correlation with laboratory ADAMTS 13 analysis and clinical features. Br. J. Haematol. 2008; 142: 819–826.
• 17. Tuncer H.H., Oster R.A., Huang S.T., Marques M.B.: Predictors of response and relapse in a cohort of adults with thrombotic thrombocytopenic purpura-haemolytic uremic syndrome: a single-institution experience. Transfusion 2007; 47: 107–114.
• 18. Cataland S.R., Wu H.M.: Atypical hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: clinically differentiating the thrombotic microangiopathies. Eur. J. Intern. Med. 2013; 24: 486–491.
• 19. Coppo P., Wolf M., Veyradier A. i wsp.: Prognostic value of inhibitory anti-ADAMTS13 antibodies in adult-acquired thrombotic thrombocytopenic purpura. Br. J. Haematol. 2006; 132: 66–74.
• 20. Ferrari S., Scheiflinger F., Rieger M. i wsp.: Prognostic value of anti-ADAMTS 13 antibody features (Ig isotype, titer, and inhibitory effect) in a cohort of 35 adult French patients undergoing a first episode of thrombotic microangiopathy with undetectable ADAMTS 13 activity. Blood 2007; 109: 2815–2822.
• 21. Loof A.H., van Vliet H.H., Kappers-Klunne M.C.: Low activity of von Willebrand factor-cleaving protease is not restricted to patients suffering from thrombotic thrombocytopenic purpura. Br. J. Haematol. 2001; 112: 1087–1088.
• 22. Moore J.C., Hayward C.P., Warkentin T.E., Kelton J.G.: Decreased von Willebrand factor protease activity associated with thrombocytopenic disorders. Blood 2001; 98: 1842–1846.
• 23. Bianchi V., Robles R., Alberio L. i wsp.: Von Willebrand factor- cleaving protease (ADAMTS13) in thrombocytopenic disorders: a severely deficient activity is specific for thrombotic thrombocytopenic purpura. Blood 2002; 100: 710–713.
• 24. Coppo P., Schwarzinger M., Buffet M. i wsp.: Predictive features of severe acquired ADAMTS13 deficiency in idiopathic thrombotic microangiopathies: the French TMA reference center experience. PLoS One 2010; 5: e10208.
• 25. Kremer Hovinga J.A., Vesely S.K., Terrell D.R. i wsp.: Survival and relapse in patients with thrombotic thrombocytopenic purpura. Blood 2010; 115: 1500–1511.
• 26. Scully M., Gattens M., Khair K., Liesner R.: The use of intermediate purity factor VIII concentrate BPL 8Y as prophylaxis and treatment in congenital thrombotic thrombocytopenic purpura. Br. J. Heamatol. 2006; 135: 101–104.
• 27. Loirat C., Veyradier A., Girma J.P. i wsp.: Thrombotic thrombocytopenic purpura associated with von Willebrand factorcleaving protease (ADAMTS13) deficiency in children. Semin. Thromb. Hemost. 2006; 32: 90–97.
• 28. Fujimura Y., Matsumoto M., Isonishi A. i wsp.: Natural history of Upshaw–Schulman syndrome based on ADAMTS13 gene analysis in Japan. J. Thromb. Haemost. 2011; 9 (suppl. 1): 283–301.
• 29. Karpman D., Sartz L., Johnson S. i wsp.: Pathophysiology of typical hemolytic uremic syndrome. Semin. Thromb. Hemost. 2010; 36: 575–585.
• 30. Kerr H., Richards A.: Complement-mediated injury and protection of endothelium: lessons from atypical haemolytic uraemic syndrome. Immunobiology 2012; 217: 195–203.
• 31. Serrano A., Xicoy B., Grifols J.R., Ribera J.M.: [Thrombotic thrombocytopenic purpura during treatment with interpheron]. Med. Clin. (Barc.) 2007; 128: 276–277.
• 32. Zheng X.L., Kaufman R.M., Goodnough L.T., Sadler J.E.: Effect of plasma exchange on plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonidiopathic thrombotic thrombocytopenic purpura. Blood 2004; 103: 4043–4049.
• 33. Zuber J., Fakhouri F., Roumenina L.T. i wsp.; French Study Group for a HCG: Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies. Nat. Rev. Nephrol. 2012; 8: 643–657.
• 34. Froissart A., Buffet M., Veyradier A. i wsp.: 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: 104–111.

• Document Type: article