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Gerinnungsveränderungen beim hämolytisch-urämischen Syndrom (HUS)

  • Conference paper
27. Hämophilie-Symposion Hamburg 1996

  • 63 Accesses

Zusammenfassung

Das Krankheitsbild des hämolytisch-urämischen Syndroms (HUS) mit der klinischen Trias Anämie, Thrombozytopenie, Nierenversagen wurde auch hämostaseologisch ausgiebig untersucht, da die Thrombosierung renaler Mikrogefäße als konstanter Befund erkannt wurde. Die Ergebnisse sind jedoch verwirrend (Tabelle 1). Von den zahlreichen Gerinnungsuntersuchungen bleibt als einzig konstantes Ergebnis die Thrombozytopenie, der erhöhte v.-Willebrand-Faktor (vWF) und das normale Fibrinogen übrig. Befunde über erhöhte Plättchenaggregation und verminderte Fibrinolyse ließen sich bei den meisten Patienten nicht substantiieren. Entsprechend waren die Hypothesen über auslösende Faktoren nicht einheitlich (s. Übersicht). So wurden eine gesteigerte Gerinnung, eine verminderte Fibrinolyse und eine gesteigerte Hämolyse mit Freisetzung thrombophiler Substanzen als Hypothesen diskutiert. Andere Autoren postulierten einen unbekannten thrombogenen Faktor, der eine disseminierte intravasale Koagulation (DIC) auslöst. Wieder andere stellten die Plättchen ins Zentrum des Geschehens und postulierten unbekannte plättchenaggregierende Substanzen, die die Bildung eines Plättchen-thrombus bewirken. Für alle Hypothesen fanden sich Hinweise, die aber insgesamt nicht das Gesamtbild erklären konnten: Entsprechend waren therapeutische Versuche mit Heparin, Plättchenaggregationshemmern, Fibrinolytika oder mit körpereigenen, die Fibrinolyse steigernden Substanzen nach den Anfangserfolgen auf Dauer nicht erfolgreich (Übersicht [1]).

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Literatur

  1. Gordjani N, Sutor AH, Zimmerhackl LB, Brandis M (1997) Hemolytic uremic syndromes. Semin Thromb Hemost 23: 281–293

    Article  PubMed  CAS  Google Scholar 

  2. Gasser C, Gautier C, Steck A, Siebenmann RE, Oechslin R (1955) Hämolytisch-urämische Syndrome: Bilaterale Nierenrindennekrose bei akuten erworbenen hämolytischen Anämien. Schw Med Wochenschr 85: 905–909

    Google Scholar 

  3. Gordjani N, Leititis JU, Zimmerhackl LB, Brandis M (1994) Hämolytisch-urämische Syndrome. In: Kleihauer E, Kulozik AE (eds) Pädiatrische Hämatologie. Enke, Stuttgart, p 77

    Google Scholar 

  4. Siegler RL, Pavia AT, Christofferson RD, Milligan MK (1994) A 20-year population-based study of postdiarrheal hemolytic uremic syndrome in Utah. Pediatrics 94: 35–40

    PubMed  CAS  Google Scholar 

  5. Kelles A, van Dyck M, Proesmans W (1994) Childhood haemolytic uraemic syndrome: long-term outcome and prognostic features. Eur J Pediatr 153: 38–42

    Article  PubMed  CAS  Google Scholar 

  6. Katz J, Lurie A, Kaplan BS, Krawitz S, Metz J (1971) Coagulation findings in the hemolyticuremic syndrome of infancy: similarity to hyperacute renal allograft rejection. J Pediatrics 78: 426–434

    Article  CAS  Google Scholar 

  7. Sutor AH (1986) Das hämolytisch-urämische Syndrom. In: Muntean W, Borkenstein M (eds) Angiopathie and Thrombose im Kindesalter. Thieme, Stuttgart New York, p 124–127

    Google Scholar 

  8. Cochran M, Coates PTH (1994) Haemolytic-uraemic syndrome. Lancet 343: 1042–1043

    Article  Google Scholar 

  9. Gildein HP, Weisser J, Gordjani N, Hildebrandt F, Sutor AH (1996) Mechanic hemolysis and acute renal failure following percutaneous catheter occlusion of a persistent ductus arteriosus. submitted

    Google Scholar 

  10. Rubenberg ML, Bull BS, Regoeczi E, Dacie JW, Brain MC (1967) Experimental production of microangiopathic haemolytic anaemia in vivo. Lancet II: 1121–1123

    Google Scholar 

  11. Katz J, Krawitz S, Sacks PV, Levin SE, Thomson P, Levin J, Metz J (1973) Platelet, erythrocyte, and fibrinogen kinetics in the hemolytic-uremic syndrome of infancy. J Pediatrics 83: 739–748

    Article  CAS  Google Scholar 

  12. Sutor AH (1973) Thrombocyturia after aspirin. New Engl J Med 288: 794–795

    Article  PubMed  CAS  Google Scholar 

  13. Kono N, Uehara S (1975) Platelets in the human urine. New Engl J Med 293: 44–45

    PubMed  CAS  Google Scholar 

  14. Engelberg H (1989) Endothelium in health and disease. Semin Thromb Hemost 15: 178–183

    Article  PubMed  CAS  Google Scholar 

  15. Mann KG, Krishnawswamy S, Lawson JH (1992) Surface dependent hemostasis. Sem Hematology 29: 213–226

    CAS  Google Scholar 

  16. Ashkenazi S (1993) Role of bacterial cytotoxins in hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. Annual Review of Medicine 44: 11–18

    Article  PubMed  CAS  Google Scholar 

  17. O’Brien AD, Holmes RK (1987) Shiga and Shiga-like toxins. Microbiol Rev 51: 206–220

    PubMed  Google Scholar 

  18. Pickering LK, Obrig TG, Stapleton FB (1994) Hemolytic-uremic syndrome and enterohemorrhagic Escherichia coli. Pediatr Infect Dis J 13: 459–475, quiz 476

    Google Scholar 

  19. Zoja C, Corna D, Farina C, Sacchi G, Lingwood C, Doyle MP, Padhye, VV, Abbate M, Remuzzi G (1992) Verotoxin glycolipid receptors determine the localization of microangiopathic process in rabbits given verotoxin-1. J Lab Clin Medicine 120: 229–238

    CAS  Google Scholar 

  20. Obrig TG, Louise CB, Lingwood CA, Boyd B, Barley-Maloney L, Daniel TO (1993) Endothelial heterogeneity in Shiga toxin receptors and responses. J Biol Chem 268: 15484–15 488

    Google Scholar 

  21. Boys B, Lingwood C (1989) Verotoxin receptor glycolipid in human renal tissue. Nephron 51: 207–210

    Article  Google Scholar 

  22. Siegler RL (1994) Spectrum of extrarenal involvement in postdiarrheal hemolytic-uremic syndrome. J Pediatrics 125: 511–518

    Article  CAS  Google Scholar 

  23. Siegler RL (1995) The hemolytic uremic syndrome. Pediatr Clin North Am 42: 15051530

    Google Scholar 

  24. Taylor CM, Milford DV, Rose PE, Roy TC, Rowe B (1990) The expression of blood group P1 in postenteropathic haemolytic uraemic syndrome. Pediatric Nephrology 4: 59–61

    Article  PubMed  CAS  Google Scholar 

  25. Pearson JD (1994) Endothelial cell function and thrombosis. Baillieres Clinical Haematology 7: 441–462

    Article  CAS  Google Scholar 

  26. Louise CB, Obrig TG (1992) Shiga toxin-associated hemolytic uremic syndrome: combined cytotoxic effects of shiga toxin and lipopolysaccharide (endotoxin) on human vascular endothelial cells in vitro. Infection & Immunity 60: 1536–1543

    CAS  Google Scholar 

  27. Remuzzi G, Ruggenenti P (1995) The hemolytic uremic syndrome. Kidney Int 48: 2–19

    Article  PubMed  CAS  Google Scholar 

  28. Kaye SA, Louise CB, Boyd B, Lingwood CA, Obrig TG (1993) Shiga toxin-associated hemolytic uremic syndrome: interleukin-1 beta enhancement of Shiga toxin cytotoxicity toward human vascular endothelial cells in vitro. Infection & Immunity 61: 3886–3891

    CAS  Google Scholar 

  29. Endo Y, Tsurugi K, Yutsudo T, Takeda Y, Ogaswara T, Igarashi K (1988) Site of action of verotoxin (VT2) from Escherichia coli O157:H7 and of shigatoxin on eucariotic ribosomes. EurJ Biochem 171: 45–50

    Article  CAS  Google Scholar 

  30. Louise CB, Obrig TG (1991) Shiga toxin-associated hemolytic uremic syndrome: Combined cytotoxic effects of Shiga toxin, interleukin-1 b, and tumor necrosis factor alpha on human vascular endothelial cells in vitro. Infect Immun 59: 4173–4179

    PubMed  CAS  Google Scholar 

  31. Brandis U, Gordjani N, Schweer H, Noltes S, Seyberth HW (1992) Hämolytisch-urämisches Syndrom: klinischer Verlauf; Thromboxanausscheidung and Verotoxinnachweis. Monatsschr Kinderheilk 140: 137 (abstract)

    Google Scholar 

  32. Seyberth HJ, Leonhard A, Tonshoff B, Gordjani N (1991) Prostanoids in pediatric kidney diseases. Pediatr Nephrol 5: 639–649

    Article  PubMed  CAS  Google Scholar 

  33. Benigni Remuzzi G (1994) The role of eicosanoids in the pathogenesis of hemolytic uremic syndrome. Prostagl Leukotr & Ess Fatty Acids 51: 75–79

    Google Scholar 

  34. Taylor CM, Lote CJ (1993) Prostacyclin in diarrhoea-associated haemolytic uraemic syndrome. Pediatr Nephrol 7: 515–519

    Article  PubMed  CAS  Google Scholar 

  35. Noris M, Benigni A, Siegler R, Gaspari F, Casiraghi F, Mancini MLX, Remuzzi G (1992) Renal prostacyclin biosynthesis is reduced in children with hemolytic-uremic syndrome in the context of systemic platelet activation. Am J Kidney Diseases 20: 144–149

    CAS  Google Scholar 

  36. Remuzzi G, Misiani R, Marchesi D, Livio M, Meca G, Degaetano G, Donati MB (1978) Haemolytic uraemic syndrome: deficiency of plasma factor(s) regulating prostacyclin activity? Lancet 2: 871–872

    Article  PubMed  CAS  Google Scholar 

  37. Chen YC, McLeod B, Hall ER, Wu KK (1981) Accelerated prostacyclin degradation in thrombotic thrombocytopenic purpura. Lancet 2: 267–269

    Article  PubMed  CAS  Google Scholar 

  38. Wu KK, Hall ER, Rossi EC, Papp AC (1985) Serum prostacyclin binding defects in thrombotic thrombocytopenic purpura. J Clin Invest 75: 168–174

    Article  PubMed  CAS  Google Scholar 

  39. Karpman D, Andreasson A, Thyssel H, Kaplan BS, Svanborg C (1995) Cytokines in childhood hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. Pediatr Nephrol 9: 694–699

    Article  PubMed  CAS  Google Scholar 

  40. Inward CD, Pall AA, Adu D, Milford DV, Taylor CM (1995) Soluble circulating cell adhesion molecules in haemolytic uraemic syndrome. Pediatr Nephrol 9: 574–578

    Article  PubMed  CAS  Google Scholar 

  41. Moake JL (1992) von Willebrand Factor Abnormalities in Thrombotic Thrombocytopenic Purpura and the Hemolytic Uremic Syndrome. In: Kaplan BS, Trompeter RS, Moake JL (eds) Hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. Marcel Dekker, New York Basel Hong Kong, p 459

    Google Scholar 

  42. Moake JL, Rudy CK, Troll ICH, Weinstein MJ, Colannino NM, Azocar J, Seder RH, Hong SL, Deykin D (1982) Unusually large plasma factor VIII: von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura. New Engl J Med 307: 1432–1435

    Article  PubMed  CAS  Google Scholar 

  43. Moake JL, Turner NA, Stathopoulos NA, Nolasco L. Hellums JD (1986) Involvment of large plasma von Willebrand Factor (vWF) multimers and unusually large vWF forms derived from endothelial cells in shear stressinduced platelet aggregation. J Clin Invest 78: 1456–1461

    CAS  Google Scholar 

  44. Benigni A, Boccardo P, Noris M, Remuzzi G, Siegler RL (1992) Urinary excretion of platelet-activating factor in haemolytic uraemic syndrome. Lancet 339: 835–836

    Article  PubMed  CAS  Google Scholar 

  45. Rose E, Enayat SM, Sunderland R, Short PE, Williams CE, Hill FGH (1984) Abnormalities of factor VIII related multimers in the haemolytic uraemic syndrome. Arch Dis Child 59: 1135–1140

    Article  PubMed  CAS  Google Scholar 

  46. Zimmerhackl LB, Thomas KB, Zehenter A, Grohmann A, Brandis M, Sutor AH (1994) Alteration of the von Willebrand Factor in Children with Hemolytic Uremic Syndrome. In: Karmali MA, Cogli AG (eds) Recent Advances in Verocytotoxin-Producing Escherichia Coli Infections. Elsevier Science, Amsterdam Lausanne New York Oxford Shannon Tokyo, p 333

    Google Scholar 

  47. Moake JL (1994): Haemolytic-uraemic syndrome: basic science. Lancet 343: 393–397

    Article  PubMed  CAS  Google Scholar 

  48. Morigi M, Zoja C, Figliuzzi M, Remuzzi G, Remuzzi A (1993) Supernatant of endothelial cells exposed to laminar flow inhibits mesangial cell proliferation. Am J Physiol 264: C1080 - X1083

    PubMed  CAS  Google Scholar 

  49. Siegler RL, Edwin SS, Christofferson RD, Mitchell MD (1991) Endothelin in the urine of children with the hemolytic uremic syndrome. Pediatrics 88: 1063–1066

    PubMed  CAS  Google Scholar 

  50. Roccatello D, Mossor R, Ferro M, Polloni R, De Filippi PGX, Quattrocchio G, Bancale E, Cesano G, Sena LM, Piccoli G (1994) Urinary endothelin in glomerulonephritis patients with normal renal function. Clinical Nephrology 41: 323–330

    PubMed  CAS  Google Scholar 

  51. Komeyama T, Takeda M, Katayama Y, Tsutsui T, Mizusawa T, Takahashi H, Hatano A, Obara K, Sato S (1993) Value of urinary endothelin-1 in patients with primary vesicoureteral reflux. Nephron 65: 537–540

    Article  PubMed  CAS  Google Scholar 

  52. Sutor AH, Hoever C (1980) Ein neuer in vivo-Test zur Beurteilung der Hämostase. In: Deutsch E, Lechner K (eds) Fibrinolyse, Thrombose, Hämostase. Schattauer, Stuttgart, p 367

    Google Scholar 

  53. Renaud C, Niaudet P, Gagnadoux MF, Broyer M, Habib R (1995) Haemolytic uraemic syndrome: prognostic factors in children over 3 years of age. Pediatr Nephrol 9: 24–29

    Article  PubMed  CAS  Google Scholar 

  54. Rowe PC, Orrbine E, Wells GA, McLaine P (1991) Epidemiology of hemolytic uremic-syndrome in Canadian children from 1987 to 1988. J Pediatrics 119: 218–224

    Article  CAS  Google Scholar 

  55. Volk T, Ioannidis I, Hensel M, Degroot H, Kox WJ (1995) Endothelial damage induced by nitric oxide: synergism with reactive oxygen species. Biochemical & Biophysical Research Communications 213: 196–203

    Article  CAS  Google Scholar 

  56. Fitzpatrick MM, Shah V (1992) Interleukin-8 and polymorphoneutrophil leucocyte activation in hemolytic uremic syndrome of childhood. Kidney Int 42: 951–956

    Article  PubMed  CAS  Google Scholar 

  57. Morigi M. Micheletti G, Figliuzzi M, Imberti B, Karmali MA, Remuzzi A, Zoja C (1995) Verotoxin-1 promotes leukocyte adhesion to cultured endothelial cells under physiologic flow conditions. Blood 86: 4553–4558

    Google Scholar 

  58. Macconi D, Foppolo M, Paris S, Noris M, Aiello S, Remmuzzi G, Remuzzi A (1995) mediates neutrophil adhesion to thrombin or TNF-stimulated endothelial cells under shear stress. Am J Physiol 269: C42 - C47

    Google Scholar 

  59. Turi S, Nemeth I, Vargha I, Matkovics B (1994) Oxidative damage of red blood cells in haemolytic uraemic syndrome. Pediatric Nephrology 8: 26–29

    Article  PubMed  CAS  Google Scholar 

  60. Situnayake RD, Crump BJ, Thurnham DI, Taylor CM (1991) Further evidence of lipid peroxidation in postenteropathic haemolytic-uraemic syndrome. Pediatr Nephrol 5: 387392

    Google Scholar 

  61. Bergstein JM, Riley M, Bang NU (1992) Role of plasminogen-activator inhibitor type 1 in the pathogenesis and outcome of the hemolytic uremic syndrome. New Engl J Med 327: 755–759

    Article  PubMed  CAS  Google Scholar 

  62. Van de Kar NC, Van Hinsbergh VW, Brommer EJ, Monnens LA (1994) The fibrinolytic system in the hemolytic uremic syndrome: in vivo and in vitro studies. Pediatric Research 36: 257–264

    Google Scholar 

  63. Bergstein JM, Kuederli U, Bang NU (1982) Plasma inhibitor of glomerular fibrinolysis in the hemolytic-uremic syndrome. American Journal of Medicine 73: 322–327

    Article  PubMed  CAS  Google Scholar 

  64. Menzel D, Levi M, Dooijewaard G, Peters M, Ten Cate JW (1994) Impaired fibrinolysis in the hemolyticuremic syndrome of childhood. Annals of Hematology 68: 43–48

    Article  PubMed  CAS  Google Scholar 

  65. Vitacco M, Sanchez Avalos J, Gianantonio CA (1973) Heparin therapy in the hemolyticuremic syndrome. J Pediatrics 83: 271–275

    Article  CAS  Google Scholar 

  66. Loirat C, Beaufils F, Sonsino E, Schlegel N, Guesnu M, Pillion GX, Andre JL, Broyer M, Guyot C, Habib R et al (1984) Treatment of childhood hemolytic-uremic syndrome with urokinase. Cooperative controlled trialt Archives Francaises de Pediatric 41: 15–19

    CAS  Google Scholar 

  67. Sutor AH, Schindera F, Jacobi H, Kunzer W (1972) Haemolytic-uraemic syndrome: thrombocyturia after treatment with streptokinase and aspirin. Lancet 2: 762

    Article  PubMed  CAS  Google Scholar 

  68. Van Damme-Lombaerts R, Proesmans W, van Damme B, Eeckels R, Binda KI, Muaka P, Mercieca V, Vlietinck R, Vermylen J (1988) Heparin plus dipyridamole in childhood hemolytic-uremic syndrome: a prospective, randomized study. J Pediatrics 113: 913–918

    Article  Google Scholar 

  69. Hayward CP, Sutton DM, Carter WH Jr, Campbell ED, Scott JG, Francombe WH, Shumak KH, Baker MA (1994) Treatment outcomes in patients with adult thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Archives of Internal Medicine 154: 982–987

    Article  PubMed  CAS  Google Scholar 

  70. Bell WR, Braine HG, Ness PM, Kickler TS (1991) Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. New Engl J Med 325: 398–403

    Article  PubMed  CAS  Google Scholar 

  71. Gianviti A, Perna A, Caringella A, Edefonti A, Penza R, Remuzzi GX, Rizzoni G (1993) Plasma exchange in children with hemolytic-uremic syndrome at risk of poor outcome. Am J Kidney Diseases 22: 264–266

    CAS  Google Scholar 

  72. Sarode R, McFarland JG, Flomenberg N, Casper JT, Cohen EP, Drobyski WR, Ash RC, Horowitz MM, Camitta B, Lawton C et al (1995) Therapeutic plasma exchange does not appear to be effective in the management of thrombotic thrombocytopenic purpura/ hemolytic uremic syndrome following bone marrow transplantation. Bone Marrow Transplantation 16: 271–275

    PubMed  CAS  Google Scholar 

  73. Brain MC, Dacie JV, Hourihane DO (1972) Microangiopathic haemolytic anaemia: Possible role of vascular lesions in pathogenesis. Br J Haematol 8: 358–374

    Google Scholar 

  74. Remuzzi G, Meca G, Livio M et al (1980) Prostacyclin generation by cultured endothelial cells in haemolyticuraemic syndrome. Lancet 1: 656–657

    Article  PubMed  CAS  Google Scholar 

  75. Forsyth KV, Simpson AC, Fitzpatrick MM, Barratt TM, Levinsky RL (1989) Neutrophilmediated Endothelial Injury in Haemolytic Uraemic Syndrome. Lancet II: 411–413

    Google Scholar 

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Authors
  1. A. H. Sutor
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  2. N. Gordjani
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Editors and Affiliations

  1. Zentr. d. Inn. Med., Med. Klinik I, Universitätsklinikum, Theodor-Stern-Kai 7, D-60590, Frankfurt am Main, Deutschland

    Inge Scharrer

  2. Hämostaseologische Abteilung, Med. Univ.-Klinik Innenstadt, Ziemssenstraße 1a, D-80336, München, Deutschland

    Wolfgang Schramm

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Sutor, A.H., Gordjani, N. (1998). Gerinnungsveränderungen beim hämolytisch-urämischen Syndrom (HUS). In: Scharrer, I., Schramm, W. (eds) 27. Hämophilie-Symposion Hamburg 1996. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-80403-8_19

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  • DOI: https://doi.org/10.1007/978-3-642-80403-8_19

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