Thrombotisch-thrombozytopenische Purpura im Kindesalter

Zusammenfassung

Die thrombotisch-thrombozytopenische Purpura (TTP) ist eine mikroangiopathische Erkrankung, die durch einen Mangel der von-Willebrand-Faktor-spaltenden Protease (VWF-CP) ADAMTS13 verursacht wird. Unterschieden werden eine familiäre und eine erworbene Form der TTP. Der familiären TTP liegen Mutationen im ADAMTS13-Gen zugrunde. Die erworbene TTP wird durch Autoantikörper gegen die von-Willebrand-Faktor-spaltende Protease ausgelöst. Im Kindesalter tritt die familiäre Form häufiger als die erworbene auf. Dabei manifestiert sich die TTP oft in nur oligosymptomatischen Verläufen. Hierdurch kann die Erkrankung leicht mit einer immunthrombozytopenischen Purpura (ITP) oder einem Evans-Syndrom verwechselt werden. Eine prompte Diagnosestellung des VWF-CP-Mangels ist wichtig, da den abortiven Episoden der TTP schwere lebensbedrohliche Schübe mit dem Vollbild der Symptome folgen können. Weitere Anstrengungen sind notwendig, um für die Patienten mit einem VWF-CP-Mangel eine risikoadaptierte Therapie zu etablieren.

Summary

Thrombotic thrombocytopenic purpura (TTP) is a microangiopathic disease due to deficiency of the specific VWF cleaving protease (VWF-CP) ADAMTS13. The acquired form is caused by autoantibodies against VWF-CP, whereas mutations of the ADAMTS13 gene are responsible for inherited TTP. In childhood both forms exist with predominance of inherited TTP. The phaenotype of TTP in childhood can be rather variable. Besides the classical clinical picture, abortive forms may occur that can delay the identification of patients at risk. The patients are frequently assumed to suffer from idiopathic thrombocytopenia (ITP) or Evans syndrome. Further efforts are necessary to accelerate correct diagnosis and to establish a risk-adapted prophylactic therapy.

Schlüsselwörter

TTP - Kinder - Evans-Syndrom - ADAMTS13

Keywords

TTP - children - Evans syndrome - ADAMTS13

• Literatur

• 1 Amorosi EL, Ultmann JE. Thrombotic thrombocytopenic purpura: Report of 16 cases and review of the literature. Medicine 1966; 45: 139-59.
• 2 Asada Y, Sumiyoshi A, Hayashi T. et al. Immunohistochemistry of vascular lesion in thrombotic thrombocytopenic purpura, with special reference to factor VIII related antigen. Thromb Res 1985; 53: 836-44.
• 3 Barbot J, Costa E, Guerra M. et al. Ten years of prophylaktic treatment with fresh-frozen plasma in a child with chronic relapsing thrombotic thrombocytopenic purpura as a result of congenital deficiency of von Willebrand factor-cleaving protease. Br J Haematol 2001; 113: 649-51.
• 4 Bell WR, Braine HG, Ness PM. et al. Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: clinical experience in 108 patients. New Engl J Med 1991; 325: 398-403.
• 5 Dacie JV, Mollison PL, Richardson N. et al. Atypical congenital haemolytic anaemia. Quart J Med 1953; 22: 79-98.
• 6 Fujikawa K, Suzuki H, McMullen B. et al. Purification of human von Willebrand factor-cleaving protease and its identification as a new member of the metalloproteinase family. Blood 2001; 98: 1662-6.
• 7 Furlan M, Lämmle B. Aetiology and pathogenesis of thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome: the role of von Willebrand factor-cleaving protease. Best Pract Res Clin Haematol 2001; 14: 437-54.
• 8 Furlan M, Robles R, Galbusera M. et al. Von Willebrand-factor cleaving protease in thrombotic thrombocytopenic purpura and the haemolytic uraemic syndrome. New Engl J Med 1998; 339: 1578-84.
• 9 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; 87: 4223-34.
• 10 Furlan M, Robles R, Morselli B. et al. Recovery and half-life of von Willebrand factor-cleaving protease after plasma therapy in patients with thrombotic thrombocytopenic purpura. Thromb Haemost 1999; 81: 8-13.
• 11 Gerritsen HE, Robles R, Lammle B. et al. Partial amino acid sequence of purified von Willebrand factor-cleaving protease. Blood 2001; 98: 1654-61.
• 12 Kentouche K, Budde U, Furlan M. et al. Remission of thrombotic thrombocytopenic purpura in a patient with compound heterozygous deficiency of von Willebrand factor-cleaving protease by infusion of solvent/detergent plasma. Acta Paediatr 2002; 91: 1056-9.
• 13 Levy GG, Nichols WC, Lian EC. et al. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature 2001; 413: 488-94.
• 14 Mannucci PM, Canciani MT, Forza I. et al. Changes in health and disease of the metalloprotease that cleaves von Willebrand factor. Blood 2001; 98: 2730-5.
• 15 Moake JL. Thrombotic microangiopathies. New Engl J Med 2002; 347: 589-600.
• 16 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; 307: 1432-5.
• 17 Moschcowitz E. Hyaline thrombosis of the terminal arterioles and capillaries: a hitherto undescribed disease. Proc N Y Pathol Soc 1924; 24: 21-4.
• 18 Savasan S, Taub JW, Buck S. et al. Congenital microangiopathic hemolytic anemia and thrombocytopenia with unusually large von Willebrand factor multimers and von Willebrand-factor cleaving protease. J Pediatr Hematol Oncol 2001; 23: 364-7.
• 19 Schneppenheim R, Budde U, Oyen F. et al. Von Willebrand factor cleaving protease and ADAMTS13 mutations in childhood TTP. Blood 2003; 101: 1845-50.
• 20 Schulman I, Pierce M, Lukens A. et al. Studies on thrombopoiesis. I. A factor in normal human plasma required for platelet production; chronic thrombocytopenia due to its deficiency. Blood 1960; 16: 943-57.
• 21 Soejima K, Mimura N, Hirashima M. et al. A novel human metalloprotease synthesized in the liver and secreted into the blood: possibly, the von Willebrand factor-cleaving protease?. J Biochem 2001; 130: 475-80.
• 22 Studt JM, Böhm M, Budde U. et al. Measurement of von Willebrand factor-cleaving protease (ADAMTS-13) activity in plasma: a multicenter comparison of different assay methods. J Thromb Haemost 2003; 1: 1882-7.
• 23 Török TJ, Holman RC, Chorba TL. Increasing mortality from thrombotic thrombocytopenic purpura in the United States – analysis of national mortality data, 1968-1991. Am J Hematol 1995; 50: 84-90.
• 24 Tsai HM. Physiologic cleavage of von Willebrand factor by a plasma protease is dependent on its conformation and requires calcium ion. Blood 1996; 87: 4235-44.
• 25 Upshaw Jr. JD. Congenital deficiency of a factor in normal plasma that reverses microangiopathic hemolysis and thrombocytopenia. N Engl J Med 1978; 298: 1350-2.
• 26 Wallace DC, Lovric A, Clubb JS. et al. Thrombotic thrombocytopenic purpura in four siblings. Am J Med 1975; 58: 724-34.