Thrombophile Gerinnungsstörungen

  • I. Pabinger


Unter dem Begriff »Thrombophilie« werden diejenigen Störungen zusammengefaßt, bei denen mit einem erhöhten Risiko für venöse Thrombosen und Embolien zu rechnen ist. Im allgemeinen wird die Bezeichnung Thrombophilie für die Thromboseneigung des venösen Schenkels des Gefäßsystems verwendet, bei bestimmten Formen der Thrombophilie können jedoch auch gehäuft Thrombosen in der arteriellen Gefäßbahn auftreten, insbesondere in den Hirnarterien und Herzkranzgefäßen.


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  1. 1.
    Auberger K (1992) Evaluation of a new protein-C concentrate and comparison of protein-C assays in a child with congenital protein-C deficiency. Ann Hematol 64: 146 – 151PubMedCrossRefGoogle Scholar
  2. 2.
    Barbui T, Finazzi G, Viganò S, Mannucci PM (1984) L-asparaginase lowers protein C antigen. Thromb Haemostas 52:– 216Google Scholar
  3. 3.
    Baudo F, DeGasperi A, deCataldo F, Caimi TM, Cattaneo D, Redaelli R, Pannacciulli E, Corti A, Mazza E, Belli L (1992) Antithrombin III supplementation during orthotopic liver transplantation in cirrhotic patients: a randomized trial. Thromb Res 68: 409 – 416PubMedCrossRefGoogle Scholar
  4. 3a.
    Bergmann F, Hoyer PF, Vigano D’Angelo S, Mazzola G, 0estereich C, Barthels M, D’Angelo A (1995) Severe autoimmune protein S deficiency in boy with idiopathic purpura fulminans. Br J Haemat 89: 610 – 614CrossRefGoogle Scholar
  5. 4.
    Blauhut B, Kramar H, Vinazzer H, Bergmann H (1985) Substitution of antithrombin III in shock and DIC: a randomized study. Thromb Res 39: 81 – 89PubMedCrossRefGoogle Scholar
  6. 5.
    Branson HE, Katz J, Marble R, Griffin JH (1983) Inherited protein C deficiency and coumarinresponsive chronic relapsing purpura fulminans in a newborn infant. Lancet ii: 1165 – 1168Google Scholar
  7. 6.
    Broekmans AW, Bertina RM, Loeliger EA, Hofman V, Klinge-mann HG (1983) Protein C and the development of skin necrosis during anticoagulant therapy. Thromb Haemostas 49: 244Google Scholar
  8. 7.
    Broekmans AW, Veltkamp JJ, Bertina RM (1983) Congenital protein C deficiency and venous thromboembolism. A study in three Dutch families. N Engl J Med 309: 340–344PubMedCrossRefGoogle Scholar
  9. 8.
    Buller HR, Ten Cate JW (1983) Antithrombin III infusion in patients undergoing peritoneovenous shunt operation: failure in the prevention of disseminated intravascular coagulation. Thromb Haemostas 49: 128 – 131Google Scholar
  10. 9.
    Buller HR, Ten Cate JW (1989) Acquired antithrombin III deficiency: laboratory diagnosis, incidence, clinical implications, and treatment with antithrombin III concentrate. Am J Med 87 [Suppl 3 B]Google Scholar
  11. 10.
    Conard J, Horellou MH, van Dreden P, Lecompte T, Samama M (1990) Thrombosis and pregnancy in congenital deficiencies in Antithrombin III, protein C or protein S: study of 78 women. Thromb Haemostas 63: 319–320Google Scholar
  12. 11.
    Conard J, Bauer KA, Gruber A, Griffin JH, Schwarz HP, Horellou MH, Samama MM, Rosenberg RD (1993) Normalization of markers of coagulation activation with a purified protein C concentrate in adults with homozygous protein C deficiency. Blood 82: 1159 – 1164Google Scholar
  13. 12.
    Dahlbäck B (1995) Inherited thrombophilia: resistance to activated protein C as a pathogenic factor of venous thromboembolism. Blood 85: 607–614Google Scholar
  14. 12a.
    D’Angelo A, Della Valle P, Crippa L, Pattarini E, Grimaldi LME, Vigano D’Angelo S (1993) Autoimmune protein S deficiency in a boy with severe thromboembolic disease. N Engl J Med 328: 1753–1757Google Scholar
  15. 13.
    De Stefano V, Mastrangelo S, Schwarz HP, Pola P, Flore R, Bizzi B, Leone G (1993) Replacement therapy with a purified protein C concentrate during initiation of oral anticoagulation in severe protein C congenital deficiency. Thromb Haemostas 7o: 247–249Google Scholar
  16. 14.
    Deutsch E, Frischauf H, Grunberger V (195o) Zwischenfälle der Dicumarolbehandlung and ihre Therapie. Z Klin Med 147: 324–333Google Scholar
  17. 15.
    Dreyfus M, Magny JF, Bridey F, Schwarz HP, Planché C, De-han M, Tchernia G (1991) Treatment of homozygous protein C deficiency and neonatal purpura fulminans with a purified protein C concentrate. N Engl J Med 325: 1565 –1568PubMedCrossRefGoogle Scholar
  18. 16.
    Engesser L, Broekmans AW, Briet E, Brommer EJP, Bertina RM (1987) Hereditary protein S deficiency: clinical manifestations. Ann Intern Med 106: 677 – 682PubMedCrossRefGoogle Scholar
  19. 17.
    Esmon CT (1992) The protein C anticoagulant pathway. Arterioscler Thromb 12: 135–145PubMedCrossRefGoogle Scholar
  20. 18.
    Esmon C, Schwarz HP. An update on clinical and basic aspects of the protein C anticoagulant pathway (in press)Google Scholar
  21. 19.
    Estellés A, Garcia-Plaza I, Dag. A, Aznar J, Duart M, Sanz G, Pérez-Requejo JL, Espana F, Jimenez C, Abeledo G (1984) Severe inherited »homozygous« protein C deficiency in a newborn infant. Thromb Haemostas 52: 53–56Google Scholar
  22. 20.
    Feinstein DI (1985) Lupus anticoagulan, thrombosis, and fetal loss. N Engl J Med 313: 1348–1350PubMedCrossRefGoogle Scholar
  23. 21.
    Finazzi G, Caccia R, Barbui T (1987) Different prevalence of thromboembolism in the subtypes of congenital antithrombin III deficiency: review of 404 cases. Thromb Haemostas 58: 10–94Google Scholar
  24. 22.
    Fourrier F, Lestavel P, Chopin C, Marey A, Goudemand J, Rime A, Mangaloboyi J (1990) Meningococcemia and purpura fulminans in adults: acute deficiencies of proteins C and S and early treatment with antithrombin III concentrates. In-tens Care Med 16: 121 – 124CrossRefGoogle Scholar
  25. 23.
    Fourrier F, Chopin C, Huart JJ, Runge I, Caron C, Goudemand J (1993) Double-blind, placebo-controlled trial of anti-thrombin III concentrates in septic shock with disseminated intravascular coagulation. Chest 104: 882 – 888PubMedCrossRefGoogle Scholar
  26. 24.
    Francis CW, Pellegrini VD Jr, Marder VJ, Harris CM, Totter-man S, Gabriel KR, Baughman DJ, Roemer S, Burke J, Goodman TL, Evarts CMcC (1989) Prevention of venous thrombosis after total hip arthroplasty. Antithrombin III and low-dose heparin compared with dextran 40. J Bone Joint Surg 71: 327–335PubMedGoogle Scholar
  27. 25.
    French J, Montgomery RR, Foster P, Endres-Brooks J, Pietryga D, Schwarz HP, Gill JC (1993) Protein C concentrate therapy in a protein C deficient patient with superior vena cava thrombosis following bone marrow transplantation. Blood 82 [Supp11]: 398 aGoogle Scholar
  28. 26.
    Gerson WT, Dickerman JD, Bovill EG, Golden E (1993) Severe acquired protein C deficiency in purpura fulminans associated with disseminated intravascular coagulation: treatment with protein C concentrate. Pediatrics 91: 418–422PubMedGoogle Scholar
  29. 27.
    Gordon B, Haire W, Kessinger A, Duggan M, Armitage J (1991) High frequency of antithrombin 3 and protein C deficiency following autologous bone marrow transplantation for lymphoma. Bone Marrow Transplant 8: 497–502PubMedGoogle Scholar
  30. 28.
    Gruber A, Blaskó G, Sas G (1986) Functional deficiency of protein C and skin necrosis in multiple myeloma. Thromb Res 42: 579–581PubMedCrossRefGoogle Scholar
  31. 29.
    Harper PL, Williamson L, Park G, Smith JK, Carrell RW (1991) A pilot study of antithrombin replacement in intensive care management: the effects on mortality, coagulation and renal function. Transfus Med 1: 121 – 128PubMedCrossRefGoogle Scholar
  32. 30.
    Hartman KR, Manco-Johnson M, Rawlings JS, Bower DJ, Marlar RA (1989) Homozygous protein C deficiency: early treatment with warfarin. Am J Pediatr Hematol/Oncol 11: 395–401Google Scholar
  33. 31.
    Hintz G, Weil J, Buchmann S, Azzam A, Auberger K, Beck C (1987) Homozygoter Säugling in einer Sippe mit erblichem Protein C-Mangel. Klin Wochenschr 65: 576 – 580PubMedCrossRefGoogle Scholar
  34. 32.
    Koeleman BPC, Reitsma PH, Allaart CF, Bertina RM (1994) Activated protein C resistance as an additional risk factor for thrombosis in protein C-deficient families. Blood 84: 1031 – 1035PubMedGoogle Scholar
  35. 33.
    Korninger C, Klepetko W, Miholic J, Schwarz Ch, Lechner K (1987) Randomized trial of antithrombin III versus placebo in patients undergoing peritoned-venous shunt operation. Thromb Haemostas 58: 426 (Abstr)Google Scholar
  36. 34.
    Langley PG, Hughes RD, Forbes A, Keays R, Williams R (1993) Controlled trial of antithrombin III supplementation in fulminant hepatic failure. J Hepato117: 326 – 331CrossRefGoogle Scholar
  37. 35.
    Lechner K, Kyrle PA (1995) Antithrombin III concentrates — Are they clinically useful? Thromb Haemostas (in press)Google Scholar
  38. 36.
    Leclerc F, Hazelzet J, Jude B, Hofhuis W, Hue V, Martinot A, Van der Voort E (1992) Protein C and S deficiency in severe infectious purpura of children: a collaborative study of 40 cases. Intens Care Med 18: 202 – 205CrossRefGoogle Scholar
  39. 37.
    Lewandowski K, Zawilska K (1994) Protein C concentrate in the treatment of Warfarininduced skin necrosis in the protein C deficiency. Thromb Haemostas 71: 395–399Google Scholar
  40. 38.
    Manco-Johnson M, Nuss R (1992) Protein C concentrate prevents peripartum thrombosis. Am J Hematol 40: 69 – 70PubMedCrossRefGoogle Scholar
  41. 39.
    Manco-Johnson MJ, Abshire TC, Jacobson LJ, Marlar RA (1991) Severe neonatal protein C deficiency: prevalence and thrombotic risk. J Pediatr 119: 793–798PubMedCrossRefGoogle Scholar
  42. 40.
    Marciniak E, Wilson HD, Marlar RA (1985) Neonatal purpura fulminans: A genetic disorder related to the absence of protein C in blood. Blood 65: 15–20Google Scholar
  43. 41.
    Marlar RA, Endres-Brooks J, Miller C (1985) Serial studies of protein C and its plasma inhibitor in patients with disseminated intravascular coagulation. Blood 66: 59–63PubMedGoogle Scholar
  44. 42.
    Marlar RA, Montgomery RR, Broekmans AW (1989) Report on the diagnosis and treatment of homozygous protein C deficiency. Thromb Haemostas 61: 529 – 531Google Scholar
  45. 43.
    Mazzucconi MG, Gugliotta L, Leone G, Dragoni F, Mattioli Belmonte M, de Stefano V, Chistolini A, Tura S, Mandelli F (1994) Antithrombin III infusion suppresses the hypercoagulable state in adult acute lymphoblastic leukaemia patients treated with a low dose of Escherichia coli L-asparaginase. A Gimema study. Blood Coagul Fibrinolys 5: 23–28CrossRefGoogle Scholar
  46. 44.
    Melissari E, Kakkar VV (1989) Congenital severe protein C deficiency in adults. Br J Haematol 72: 222– 228PubMedCrossRefGoogle Scholar
  47. 45.
    Menache D, O’Malley JP, Schorr JB, Wagner B, Williams C, and the Cooperative Study Group (1990) Evaluation of the safety, recovery, half-life, and clinical efficacy of antithrombin III (human) in patients with hereditary antithrombin III deficiency. Blood 75: 33–39PubMedGoogle Scholar
  48. 46.
    Miletich J, Sherman L, Broze G Jr (1987) Absence of thrombosis in subjects with heterozygous protein C deficiency. N Engl J Med 317: 991– 996PubMedCrossRefGoogle Scholar
  49. 47.
    Mitchell CA, Rowell JA, Hau L, Young JP, Salem HH (1987) A fatal thrombotic disorder associated with an acquired inhibitor of protein C. N Engl J Med 317: 1638 –1642PubMedCrossRefGoogle Scholar
  50. 48.
    Muntean W, Finding K, Gamillscheg A, Zenz W (1992) Multiple thromboses and coumarininduced skin necrosis in a young child with antiphospholipid antibodies. Thromb Haemorrh Disorders 5: 43–45Google Scholar
  51. 49.
    Mustafa S, Pabinger I, Mannhalter C. PS-deficiency type I: identification of point mutations in 9 of 10 families. (Submitted)Google Scholar
  52. 50.
    Oikawa T, Muramatsu Y, Akashi S, Usui N (1993) Prophylactic use of concentrated antithrombin III preparation in children with nephrotic syndrome. Nippon Jinzo Gakkai Shi 35: 1163 – 1169PubMedGoogle Scholar
  53. 51.
    Pabinger I, Karnik R, Lechner K, Slany J, Niessner H (1986) Coumarin induced acral skin necrosis associated with hereditary protein C deficiency. Blut 52: 365– 370PubMedCrossRefGoogle Scholar
  54. 52.
    Pabinger I, Brucker S, Kyrie PA, Schneider B, Korninger C, Niessner H, Lechner K (1992) Hereditary deficiency of anti-thrombin III, protein C and protein S: prevalence in patients with a history of venous thrombosis and criteria for a rational patient screening. Blood Coagul Fibrinol 3: 547–553CrossRefGoogle Scholar
  55. 53.
    Pabinger I, Kyrie PA, Heistinger M, Eichinger S, Wittmann E, Lechner K (1994) The risk of thromboembolism in asymptomatic patients with protein C- and protein S deficiency: A prospective cohort study. Thromb Haemostas 71: 441 – 445Google Scholar
  56. 53.
    a. Pabinger I, Schneider B, and the GTH Study Group on Natural Inhibitors (1996) The thrombotic risk in hereditary anti-thrombin-, protein C- and protein S-deficiency: A cooperative retrospective study. Artherosclerosis, thrombosis and vascular biology (im Druck )Google Scholar
  57. 54.
    Palareti G, Legnani C, Maccaferri M, Gozzetti G, Mazziotti A, Martinelli G, Zanello M, Sama C, Coccheri S (1991) Coagulation and fibrinolysis in orthotopic liver transplantation: role of the recipient’s disease and use of antithrombin III. Haemostasis 21: 68 – 76PubMedGoogle Scholar
  58. 55.
    Pescatore P, Horellou HM, Conard J, Piffoux M, Van Dreden P, Ruskone-Fourmestraux A, Samama M (1993) Problems of oral anticoagulation in an adult with homozygous protein C deficiency and late onset of thrombosis. Thromb Haemostas 69: 311 – 315Google Scholar
  59. 56.
    Powlars D, Larsen R, Johnson J, Hulbert T, Sun T, Patch MJ, Francis R, Chan L (1993) Epidemic meningococcemia and purpura fulminans with induced protein C deficiency. Clin Infect Dis 17: 254 – 261CrossRefGoogle Scholar
  60. 57.
    Pui CH, Chesney CM, Bergum PW, Jackson CW, Rapaport SI (1986) Lack of pathogenetic role of proteins C and S in thrombosis associated with asparaginase-prednisone-vincristine therapy for leukaemia. Br J Haematol 64: 283 – 290PubMedCrossRefGoogle Scholar
  61. 58.
    Rivard GE, David M, Farrell C, Gerson W, Dickerman JD, Bovill EG, Schwarz HP (1993) Treatment of purpura fulminans in meningococcemia with protein C concentrate. Thromb Haemostas 69: 23–39 (Abstr)Google Scholar
  62. 59.
    Rivard GE, David M, Farrell C, Schwarz HP (1995) Treatment of purpura fulminans in meningococcemia with protein C concentrate. J Pediatr (in press)Google Scholar
  63. 6o.
    Rosove MH, Brewer PMC (1992) Antiphospholipid thrombosis: clinical course after the first thrombotic event in 7o patients. Ann Intern Med 117: 303 – 308PubMedCrossRefGoogle Scholar
  64. 61.
    Schipper HG, Ten Cate JW (1982) Antithrombin III transfusion in patients with hepatic cirrhosis. Br J Haematol 52:5–33CrossRefGoogle Scholar
  65. 62.
    Schramm W, Spannagl M, Bauer KA, Rosenberg RD, Birkner B, Linnau Y, Schwarz HP (1993) Treatment of coumarin-induced skin necrosis with a monoclonal antibody purified protein C concentrate. Arch Dermatol 129: 753–75CrossRefGoogle Scholar
  66. 63.
    Schulman S, Tengborn L (1992) Treatment of venous thromboembolism in patients with congenital deficiency of anti-thrombin III. Thromb Haemostas 68: 634 – 636Google Scholar
  67. 64.
    Schwarz HP, Nelson K, Dreyfus M, Masterson M, Montgomery R, Rivard G, David M, Kreuz W, Parapia L, Minford A, Tillyer L, Allgrove J, Conard J, Bauer K (1993) Acute and longterm treatment of severe congenital protein C deficiency with protein C concentrate. Thromb Haemostas 69: 1698 (Abstr)Google Scholar
  68. 65.
    Schwartz RS, Bauer KA, Rosenberg RD, Kavanaugh EJ, Davies DC, Bogdanoff DA (1989) Clinical experience with anti-thrombin III concentrate in treatment of congenital and acquired deficiency of antithrombin. Am J Med 87 [Suppl 3 B]: 53 S-6o SGoogle Scholar
  69. 66.
    Seligsohn U, Berger A, Abend M, Rubin L, Attias D, Zivelin A, Rapaport SI (1984) Homozygous protein C deficiency manifested by massive venous thrombosis in the newborn. N Engl J Med 310: 559–562CrossRefGoogle Scholar
  70. 67.
    Sharon C, Tirindelli MC, Mannucci PM, Tripodi A, Mariani G (1986) Homozygous protein C deficiency with moderately severe clinical symptoms. Thromb Res 41: 483– 488PubMedCrossRefGoogle Scholar
  71. 68.
    Sills RH, Marlar RA, Montgomery RR, Deshpande GN, Humbert JR (1984) Severe homozygous protein C deficiency. J Pediatr 105: 409–413PubMedCrossRefGoogle Scholar
  72. 69.
    Svensson PJ, Dahlbäck B (1994) Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 33o: 517–522PubMedCrossRefGoogle Scholar
  73. 7o.
    Tait RC, Walker ID, Perry DJ, Islam SIAM, Daly ME, McCall F, Conkie JA, Carrell RW (1994) Prevalence of antithrombin deficiency in the healthy population. BrjHaematol 87: 106–112CrossRefGoogle Scholar
  74. 71.
    Thaler E, Lechner K (1981) Antithrombin III deficiency and thromboembolism. Clin Haematol to: 369–390Google Scholar
  75. 72.
    Tuddenham EGD, Takase T, Thomas AE, Awidi AS, Madanat FF, Abu Hajir MM, Kernoff PBA, Hoffbrand AV (1989) Homozygous protein C deficiency with delayed onset of symptoms at 7 to to months. Thromb Res 53: 475–484PubMedCrossRefGoogle Scholar
  76. 73.
    Vukovich T, Auberger K, Weil J, Engelmann H, Knöbl P, Hadorn HB (1988) Replacement therapy for a homozygous protein C deficiency-state using a concentrate of human protein C and S. BrjHaematol 70: 435–440CrossRefGoogle Scholar
  77. 74.
    Wada H, Deguch K, Shirakawa S, Suzuki K (1993) Successful treatment of deep vein thrombosis in homozygous protein C deficiency with activated protein C. Am J Hematol 44: 218–219PubMedCrossRefGoogle Scholar

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