Thromb Haemost 2006; 95(06): 967-981
DOI: 10.1160/TH05-07-0489
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Heparin-induced thrombocytopenia (HIT)

A report of 1,478 clinical outcomes of patients treated with danaparoid (Orgaran) from 1982 to mid-2004
Harry N. Magnani
1   NV Organon, Oss, The Netherlands
,
Alex Gallus
2   Flinders University and Flinders Medical Centre, Adelaide, South Australia, Australia
› Author Affiliations
Further Information

Publication History

Received 12 July 2005

Accepted after resubmission 14 April 2006

Publication Date:
30 November 2017 (online)

Summary

Clinical outcomes of 1,478 danaparoid treatment case reports for HIT (involving 1,418 patients) treated between 1982 and mid-2004 are analysed. Treatment in 1,291 episodes was for current HIT. Thromboembolism due to HIT was present in 39.4a%. The patients include 33 children and 32 pregnancies. Two hundred twenty-six patients required extra-corporeal circuit use for renal failure, 241 patients had a concomitant thrombophilic disorder, and 351 major operations were performed. Clinical outcomes were assessed during danaparoid treatment (range one day to 3.5 years) plus three months of follow-up. Of the danaparoid-treated patients 83.8a% survived; 63.7a% had no or minor adverse events and 20.1a% suffered serious non-fatal adverse events. New thromboses occurred during 9.7a% of treatment episodes, and 16.4a% of treatment episodes had an inadequate treatment response (i. e. developed one or more of the following: new/extended thrombosis, persistent/new platelet count reduction, unplanned amputation during treatment and follow-up). Major bleeding was reported in 8.1a% of treatment episodes. Clinical cross-reactivity of danaparoid (new/persistent platelet count reduction and/or new/extended thrombosis) was confirmed serologically in 23 of 36 patients with positive pretreatment serological danaparoid cross-reactivity and in 22 of 32 additional patients tested at the time of the new event, i. e. a total of 45 patients (3.2a%). Clinical outcomes of these case reports of patients given danaparoid because of suspected or confirmed HIT appear to be comparable with those reported by others who used direct thrombin inhibitors, especially when a sufficient danaparoid dosing intensity was used in patients with isolated HIT. Post-operative bleeding limits danaparoid use for cardiopulmonary by-pass surgery. Routine clinical and platelet count monitoring are required to minimise adverse reactions due to cross-reactivity.

 
  • References

  • 1 Boshkov LK, Warkentin TE, Hayward CPM. et al. Heparin-induced thrombocytopenia and thrombosis: clinical and laboratory studies. Br J Haematol 1993; 84: 322-8.
  • 2 Ofosu FA. Anticoagulant mechanisms of Orgaran (Org 10172) and its fraction the high affinity to antithrombin III (Org 10849). Haemost 1992; 22: 66-72.
  • 3 Chong BH, Gallus AS, Cade JF. et al. Prospective open-label comparison of danaparoid with dextran 70 in the treatment of heparin-induced thrombocytopenia with thrombosis. Thromb Haemost 2001; 86: 1170-5.
  • 4 Warkentin TE. Limitations of conventional treatment options for heparin-induced thrombocytopenia. Seminars in Haematology 1998; 35 (Suppl. 05) 17-25.
  • 5 Warkentin TE. The treatment of heparin-induced thrombocytopenia (HIT): An historical comparison of ancrod versus danaparoid in one medical community. 65th RCPSC meeting abstract in Clin Invest Med. 1996 19. (Suppl S31): No. 240.
  • 6 Greinacher A, Janssens U, Berg G. et al. Lepirudin (recombinant hirudin) for parenteral anticoagulation in patients with heparin-induced thrombocytopenia Heparin-induced thrombocytopenia study (HAT) investigators. Circulation 1999; 100: 587-93.
  • 7 Farner B, Eichler P, Kroll H. et al. A comparison of lepirudin and danaparoid in patients with heparin-induced thrombocytopenia (HIT). Thromb Haemost 2001; 85: 950-7.
  • 8 Magnani HN. Heparin-induced thrombocytopenia (HIT): an overview of 230 patients treated with Orgarana® (Org 10172). Thromb Haemost 1993; 70: 554-61.
  • 9 Magnani HN. Orgarana® (danaparoid) use in the syndrome of heparin-induced thrombocytopenia. Platelets 1997; 08: 74-81.
  • 10 Ortel TL, Chong BH. New treatment options for heparin-induced thrombocytopenia. Sem Hematol 1998; 35 (Suppl. 05) 26-34.
  • 11 Chong BH, Magnani HN. Orgarana® in heparin-induced thrombocytopenia. Haemost 1992; 22: 85-91.
  • 12 Chong BH, Magnani HN. Danaparoid for the treatment of heparin-induced thrombocytopenia. In: Heparin-induced thrombocytopenia. 3rd Edition. Ed. Warkentin TE, Greinacher A; Marcel Dekker Inc: 2004: 371-96.
  • 13 Magnani HN, Beyering R, Cate ten JW. et al. Orgarana® anticoagulation for cardiopulmonary by-pass in patients with heparin-induced thrombocytopenia. In: New anticoagulants for the cardiovascular patient. Pifarre R; Publ Hanley and Belfus Inc. Philadelphia: 1997: 487-500.
  • 14 Harenberg J, Zimmermann R, Schwartz F. et al. Treatment of heparin-induced thrombocytopenia with thrombosis by a new heparinoid. Lancet 1983; 30: 986-7.
  • 15 Warkentin TE. Clinical picture of heparin-induced thrombocytopenia. In: Heparin-Induced thrombocytopenia. 3rd Edition. Ed. Warkentin TE, Greinacher A; Marcel Dekker Inc: 2004: 53-106.
  • 16 Alkindi S, Enright H. Successful therapy of heparin induced thrombocytopenia with alternative anticoagulants. Ir J Med Sci. 1999 168. (Suppl 3): 29 (Abstr P 94).
  • 17 Alvarez JM, Mezzatesta JP. Aprotinin and Organon 10172: a successful combination for coronary artery bypass surgery complicated by heparin-induced thrombocytopenia. Aust NZ J Surg 2000; 70: 819-21.
  • 18 Amberger HG. Heparininduzierte Thrombozytopenie Typ II mit thromboembolischen Komplikationen. Med Welt 1999; 50: 13-5.
  • 19 Andolfatto S, Latger-Cannard V, de Maistre E. et al. Naécroses cutanaées induites par la’haéparine aà propos de deux cas. Ann Biol Clin 2001; 59: 651-4.
  • 20 Anon. Heparin-induced thrombocytopenia (HIT) and new anticoagulant and antithrombotics. Case. Pharmacy Nursing Inservice. 2002
  • 21 Anon. a‘TodayI turned 5a’. Personal account. Available at www. deardiary. net. March 18. 2002
  • 22 Aoufi A, Blanc P, Piriou V. et al. Cardiac surgery with cardiopulmonary bypass in patients with Type II heparin-induced thrombocytopenia. Ann Thorac Surg 2001; 71: 678-83.
  • 23 Ariano RE, Bhattcharya SK, Moon M. et al. Failure of danaparoid anticoagulation for cardiopulmonary bypass. J Thorac Cardiovasc Surg 2000; 119: 267-8.
  • 24 Arnheim K. Diagnostische und therapeutische Massnahmen bei Heparin-induzierter Thrombozytopenie II. Haemostasiologie 2000; 20: 50-2.
  • 25 Asztely M, Larsson B, Lindgren A. et al. Komplikation vid Budd-Chiari Syndrom, Heparinbehandling orsakade trombocytopeni. Laäkartidningen 1994; 91: 3499-502.
  • 26 Barratt S McG, Ruff SJ. et al. Heparin-induced thrombocytopenia presenting after the cessation of low molecular weight heparin prophylaxis with enoxaparin. MJA 2000; 172: 449.
  • 27 Barth KSA. Inzidenz der Heparin-induzierten Thrombozytopenie Typ II am Klinikum der Justus-Liebig-Universitaät Giessen. MD Thesis, Giessen. 1998
  • 28 Baumgartel MW, Eichler P, Glockner W. et al. Heparin-induced thrombocytopenia (HIT): in vitro and in vivo cross-reactivity to danaparoid sodium and successful treatment with recombinant hirudin (lepirudin). (Letter) EurJ Haematol 2000; 65: 148-9.
  • 29 Beland B, Busse H, Loick HM. et al. Phlegmasia cerulea dolens, cerebral venous thrombosis and fatal pulmonary embolism due to heparin-induced thrombocytopenic thrombosis syndrome. Anesth Analg 1997; 85: 1272-4.
  • 30 Ben Ami R, Rachmimov S, Berliner S. Danaparoid sodium for dialysis in heparin-induced thrombocytopenia. Harefuah 1999; 136: 361-4 419..
  • 31 Benedetti-Bardet C, Chaussinand JP, Tardy B. et al. Thrombopenia with thrombosis with heparin and Danaparoid about a fatal evolution case. (Letter) Therapie 1999; 54: 297.
  • 32 Bergeron S, Demers C, Bogarty P. et al. The endocarditis that was not: an unusual case of heparin-induced thrombocytopenia with unusual complications. Can J Cardiol 2001; 17: 1180-2.
  • 33 Besien K van, Hoffman R, Golichowski A. Pregnancy associated with lupus anticoagulant and heparininduced thrombocytopenia: management with a low molecular weight heparinoid. Thromb Res 1991; 62: 23-9.
  • 34 Blakeman B. Management of heparin-induced thrombocytopenia:a cardiovascular surgeona’s perspective. Sem Hematol 1999; 36 (Suppl. 01) 37-41.
  • 35 Bleasel JF, Rasko JEJ, Rickard KA. et al. Acute adrenal insufficiency secondary to heparin-induced thrombocytopenia-thrombosis syndrome. Aust Med J 1992; 157: 192.
  • 36 Bocquet R, Blanot S, Dautzenberg MD. et al. Syndrome des anticorps antiphospholipides en neurochirurgie paédiatrique: un probleme da’haémostase. Ann Fr Anesth Raéanim 1999; 18: 991-5.
  • 37 Bondoc AY, Kapoor M. Successful thrombolysis for heparin-induced thrombocytopenia and thrombosis after hepatic resection. Chest. 2000 118. (Suppl 4): Abstr 291S.
  • 38 Boon DM, Michiels JJ, Stibbe J. et al. Heparin-induced thrombocytopenia and antithrombotic therapy. (Letter) Lancet 1994; 344: 1296.
  • 39 Boon DM, Kappers-Klunne MC, Michiels JJ. et al. Heparin-induced thrombocytopenia and thrombosis: a potential fatal complication in a routine treatment. Neth J Med 1995; 46: 146-52.
  • 40 Boshkov LH, Hamilton P, Lee A, Boldt K. Successful therapy of heparin-induced thrombocytopenia with thrombosis (HITTS) in pregnancy with danaparoid sodium. Blood 1999; 94 (Suppl. 01) 102b.
  • 41 Bredlich RO, Stracke S, Gall H. et al. Heparinassoziertes Thrombozyten-Aggregationssyndrom mit Hautnekrosen bei Haämodialyse. Dtsch med Wschr 1997; 122: 328-32.
  • 42 Bremaud M, De Maistre E, Junke E. et al. Peri-operative anticoagulation with danaparoid for a patient with Budd-Chiari syndrome and heparin-induced thrombocytopenia. Ann Fr Anesth Reanim 2004; 23: 50-5.
  • 43 Bretelle RO, Leude E. Quilici J, et al Utilisation de la’Orgarana® pour une circulation extra-corporelle chez une patiente allergique a la’haéparine. Presse Maéd 1996; 25: 1847.
  • 44 Brimhall DB. Heparin-induced thrombocytopenia and thrombosis, the a“white clot syndromea”. Poster presented at the ASIM-Missouri. 2000 Available at http://www.amsect.org/ce/HIT/HITPoster.htm
  • 45 Buerger T, Tautenhahn J, Meyer F. et al. Heparin-induced vascular occlusion in vasculosurgical patients- an evaluation of the disease in 13 patients. J Cardiovasc Surg 1999; 40: 237-42.
  • 46 Buerkhard-Meier U, Soehngen D, Schultheiss H-P. et al. Heparin-induced thrombocytopenia Type II: successful use of Orgarana® (Org 10172) in intensive care patients. Intensive Care Med 1995; 21: 542-4.
  • 47 Burke AP, Mezzetti T, Farb A. et al. Multiple coronary graft occlusion in a fatal case of heparin-induced thrombocytopenia. Chest 1998; 114: 1492-5.
  • 48 Buys S, Duterque D, Rouge P. et al. The use of danaparoid sodium in patients with heparin-induced thrombocytopenia requiring cardiac surgery with cardiopulmonary bypass is detrimental: a matched case control study. Anesthesiology 2003; 99: A-223.
  • 49 Cannell PK, Herrmann RP, Marshall L. Heparinoid during cardiopulmonary by-pass. Aust NZ J Med 1991; 21 (Suppl. 01) 141.
  • 50 Cantor WJ, Leblanc MD. Garvey, et al. Combined use of Orgarana® and Rheoproa® during coronary angioplasty in patients unable to receive heparin. Catheter Cardiovasc Interv 1999; 46: 352-5.
  • 51 Chong BH, Ismail F, Cade J. et al. Heparin-induced thrombocytopenia: studies with a new low molecular weight heparinoid, Org 10172. Blood 1989; 73: 1592-6.
  • 52 Christiansen S, Jahn UR, Meyer J. et al. Anticoagulative management of patients requiring left ventricular assist device implantation and suffering from heparininduced thrombocytopenia Type II. Ann Thorac Surg 2000; 69: 774-7.
  • 53 Christiansen S, Geiger A, Splittgerber FH. et al. Coronary artery by-pass grafting ina patient with type II heparin associated thrombocytopenia. Cardiovasc Surg 1998; 06: 90-3.
  • 54 Christin F, Thiessen-Lavat O, Loeb JP. Intaéraêt du danaparoaïde (Orgarana®) au cours de la’haémofiltration veinoveineuse continue en praésence da’une thrombopaénie a la’haéparine. Ann Fr Anesth Reanim 1998; 17: 82-3.
  • 55 Cicco NA, Gerkin G, Frey M. et al. Heparin-induced thrombocytopenia. Intensivmed. 2000 37. (Suppl 1): I/99-I/107
  • 56 Collart F, Derouck D, Kerbaul F. et al. Regression of intracardiac heparin-induced thrombosis after aortic root surgery. Ann Thorac Surg 2003; 76: 617-9.
  • 57 Dandekar U, Young J, Kalkat M. et al. Heparin-induced thrombocytopenia type II complicating coronary artery bypass surgery: a tale of caution. Interact Cardiovasc Thorac Surg 2004; 03: 121-3.
  • 58 Darling K, Jaumotte C, Saussoy P. et al. Heparin-induced thrombocytopenia complicated by arterial and venous thrombosis: report of 2 cases successfully treated by danaparoid sodium. Acta Clin Belg 2000; 55: 176-81.
  • 59 Davenport A. Management of heparin-induced thrombocytopenia during continuous renal replacement therapy. Am J Kidney Dis 1998; 32: E3.
  • 60 Davidson SJ, Burman JF, Chaubey S. et al. A patient with factor V Leiden who rapidly developed fatal heparin-induced thrombocytopenia. Thromb Haemost 2003; (Suppl. 01) Abstr No. P1170.
  • 61 Deryck YL, van Krugten RJ, Schepp RM. et al. Heparinoid Org 10172 for anticoagulation during extracorporeal circulation: a case report. Acta Anaesthesiologica Belg 1990; 41: P54.
  • 62 Doherty DC, Ortel TL, Bruijn N de. et al. Heparinfree cardiopulmonary by-pass: first reported use of heparinoid (Org 10172) to provide anticoagulation for cardio-pulmonary by-pass. Anesthesiol 1990; 73: 562-5.
  • 63 Dworschak M, Hiesmayr JM, Lassnigg A. Lifesaving citrate anticoagulation to bridge to danaparoid treatment. Ann Thorac Surg 2002; 73: 1626-7.
  • 64 Elalamy I, Lecrubier C, Potevin F. et al. Danaparoid therapy and cross-reactivity: study of 117 HIT patients. Thromb Haemost 2000; 30 (Suppl. 01) 64.
  • 65 Elzo-Kraemer CV, Sijpkens YWJ, Huisman MV. Finger gangrene, adrenal haemorrhage and deep venous thrombosis in a woman with heparin-induced thrombocytopenia (HIT) type II syndrome. Neth J Med. 2002 60. Abstr 99.
  • 66 Emig U, Meyer T, Buchwald AB. Erfolgreiche lysetherapie einer Vena-cava Inferior and Iliofemoral Venenthrombose bei Heparin-induzierte Thrombozytopenie Typ II. Dtsch med Wschr 1997; 122: 965-8.
  • 67 Espiritu JD, Creer MH, Miklos AZ. et al. Fatal tumour thrombosis due to an inferior vena cava leiomyosarcoma in a patient with antiphospholipid syndrome. Mayo Clin Proc 2002; 77: 595-9.
  • 68 Fernandes P, Mayer R, MacDonald JL. et al. Use of danaparoid sodium (Orgaran) as an alternative to heparin sodium during cardiopulmonary bypass: a clinical evaluation of six cases. Perfusion 2000; 15: 531-9.
  • 69 Fischer KG, Karger R, Nies C. et al. Heparin-induzierte Thrombozytopenie mit Todesfolge nach vorderer Exenteration wegen Harnblasenkarzinom bei Sharp-Syndrom- ein Fallbericht. Akt Urol 1998; 29: 39-42.
  • 70 Flamholz R, Tran T, Grad GI. et al. Therapeutic plasma exchange for for the acute management of the catastrophic antiphospholipid syndrome: aβ2-glycoprotein I antibodies as a marker as a response to therapy. J Clin Apheresis 1999; 14: 171-6.
  • 71 Francis JL, Palmer GJ, Moroose R. et al. Comparison of bovine and porcine heparin in heparin antibody formation after cardiac surgery. Ann Thorac Surg 2003; 75: 17-22.
  • 72 Gailani D, Reese EP. Anticoagulant-induced skin necrosis with hereditary deficiency of Protein S. AmJ Hematol 1999; 60: 231-6.
  • 73 Gerhardt A, Zotz RB, Scheja JW. et al. First successful use of danaparoid in a pregnant woman with tricuspid valve prosthesis and heparin-induced thrombocytopenia Type II (HIT TYP II). Blood. 2000 96. 95B Abstr 4093 [and abstract in Ann Hematol 2001; 80 (Suppl 1): A20].
  • 74 Gill J, Kovacs MJ. Successful use of danaparoid in treatment of heparin-induced thrombocytopenia during twin pregnancy. Obstet Gynecol 1997; 90: 648-50 [and abstract in Blood 1996; 88(Suppl 1): A20]. No 3053].
  • 75 Gillis S, Gideon M, Zahger D. et al. Danaparoid for cardiopulmonary bypass in patients with previous heparin-induced thrombocytopenia. B J Haematol 1997; 98: 657-9.
  • 76 Gindre I, Maistre E de, Perrin A. et al. Thrombopaénies sous haéparinothaérapie Utilisation du danaparoaïde (Orgaran?), trieze cas monocentriques sous le raégime de la’ATU. Thaérapie 1997; 52: 591-7.
  • 77 Girisch M, Buheitel G, Ries M. et al. Safe and effective use of danaparoid during cardiac catheterization ina 14 month old boy with tetralogy of Fallot and heparin-induced thrombocytopenia. Ann Hematol 2001; 80 (Suppl) A20 Abstr 68.
  • 78 Bidlingmaier C, Magnani HN, Girisch M. et al. Safety and efficacy of danaparoid (Orgaran) use in children. Acta Haematol 2006; 115: 237-47.
  • 79 Gitlin SD, Deeb GM, Yann C. et al. Intraoperative monitoring of danaparoid sodium anticoagulation during cardiovascular operations. J Vasc Surg 1998; 27: 568-75.
  • 80 Godet G, Bertrand M, Steen E van de. et al. Danaparoaïde and heparin-induced thrombocytopenia. Ann Fr Anesthesie Reanim 2001; 20: 50-3.
  • 81 Goti F, Gianom D, Korte W. et al. Postoperative heparin-induzierte thrombopenie mit thromboembolie (HITT) - eine seltene Komplikation der Heparintherapie. Swiss Surg 2001; 07: 51-6.
  • 82 Gottschling LL, Alaniz C. Thrombosis resulting from heparin therapy. Pharmacotherapy 1996; 16: 469-72.
  • 83 Gould J, Myers B. Prophylactic danaparoid in heparin-induced thrombocytopenia presenting with skin manifestations in pregnancy. Blood Coag Fibrinol. 2002 13. Abstr P15.
  • 84 Goyen M, Kroger K, Massalha K. et al. Schwierigkeiten in der Erkennung der Heparin-induzierten Thrombozytopenie Typ II. Schweitz Rundsch Med Praxis 1999; 88: 458-90.
  • 85 Grainger JD, Hay CRM. Heparin induced thrombocytopenia caused by danaparoid sodium. Abstract CD3458 presented at the 18th ISTH congress. Thromb Haemost. 2001 available on CD-ROM.
  • 86 Greinacher A, Michels I, Mueller-Eckhardt C. Heparin-associated thrombocytopenia: The antibody is not heparin specific. Thromb Haemost 1992; 67: 545-9.
  • 87 Greinacher A, Drost W, Michels I, Leitl J. et al. Heparin associated thrombocytopenia: successful therapy with a heparinoid (Org 10172) in a patient showing cross-reaction to LMW heparins. Ann Hematol 1992; 64: 40-2.
  • 88 Greinacher A, Philippen KH, Kemkes-Mathes B. et al. Heparin-associated thrombocytopenia type II in a patient with end-stage renal disease: successful anticoagulation with the low molecular weight heparinoid Org 10172 during haemodialysis. Nephrol Dial Transplant 1993; 08: 1176-7.
  • 89 Greinacher A, Eckhardt Th, Mussmann J. et al. Pregnancy complicated by heparin-associated thrombocytopenia: management by a prospectively in-vitro selected heparinoid (Org 10172). Thromb Res 1993; 71: 123-6.
  • 90 Grocott HP, Root J, Berkowitz SD. et al. Coagulation complicating cardiopulmonary by-pass in a patient with heparin-induced thrombocytopenia receiving the heparinoid danaparoid sodium. J Cardiothorac Vasc Anesth 1997; 11: 875-7.
  • 91 Gruel Y, Nguyen P, Pouplard C. et al. Low molecular weight heparin-induced thrombocytopenia: different from HIT due to unfractionated heparin. Blood 2000; 96: 272a-273a.
  • 92 Haas S. Chirurgische und internistische Fallbeispiele zur HIT II. J Anasth Intensivbehandl 2000; 07: 27-30.
  • 93 Haas S. Fallbeispiele zur Therapie der HIT II aus gutachterlicher Sicht. Anaesth Intensiv Notfallmed Schmerzther 2002; 37 (Suppl. 01) 17-9.
  • 94 Hach-Wunderle V, Hach W. Die Konsultation der Chirurgen bei der Kumarinnekrose. Gefaässchirurgie 1996; 01: 241-6.
  • 95 Hach-Wunderle V, Kainer K, Salzmann G. et al. Heparin-related thrombosis despite normal platelet counts in vascular surgery. Am J Surg 1997; 173: 117-9.
  • 96 Hach-Wunderle V, Kainer K. Krug, et al. Heparin associated thrombosis despite normal platelet counts. The Lancet 1994; 344: 469-70.
  • 97 Hale LP, Smith K, Braden GA. et al. Orgarana® during rotational atherectomy in the setting of heparin-induced thrombocytopenia. Catheter Cardiovasc Diagn 1998; 45: 318-22.
  • 98 Harbrecht UM, Weber D, Hertfelder H-J. et al. Low molecular weight heparin causing heparin-induced thrombocytopenia type II with severe thrombotic complications. 42nd Ann Meeting GTH. 1998 Abstr P-127.
  • 99 Harenberg J, Huhle G, Piazolo L. et al. Anticoagulation in patients with heparin-induced thrombocytopenia type II. Semin Thromb Hemost 1997; 23: 189-96.
  • 100 Henny Ch P, Cate H, Cate ten JW. et al. Thrombosis prophylaxis in an AT-III deficient woman: application of a low molecular weight heparinoid. Thromb Haemost 1986; 55: 301.
  • 101 Hermanns B, Janssens U, Handt S. et al. Pathomorphological aspects of heparin-induced thrombocytopenia II (HIT-II syndrome). Virchows Arch 1998; 432: 541-6.
  • 102 Herzog S, Rath W, Kuhn W. Successful therapy of heparin associated thrombocytopenia with a low grade sulphated heparinoid. Geburtsh Frauenheilk 1995; 55: 154-6.
  • 103 Hill GR, Hickton C, Henderson S. et al. The use of low dose Orgarana® in heparin-induced thrombocytopenia associated with in-vitro platelet aggregation at higher Orgaran concentrations. Clin Lab Haem 1997; 19: 155-7.
  • 104 Hobbensiefken G, Driller B. Studtmann, et al. Eine fatale Komplikation der medikamentaösen Thromboprophylaxe mit Heparinen. Unfallchirurgie 1996; 22: 248-52.
  • 105 Hofbauer LC, Spitzweg C, Heufelder AE. Gravea’s disease associated with primary antiphospholipid syndrome. J Rheumatol 1996; 23: 1435-7.
  • 106 Hoffmann Huhle G, Haseroth K. et al. A fatal complication ina patient with heparin-induced thrombocytopenia type II re-exposed to heparin. Eur J Orthop Surg Traumatol 1999; 09: 205-7.
  • 107 Horellou MH, Elalamy I, Achkar A. et al. Efficacy and safety of danaparoid (Orgarana®) in venous thrombosis in pregnant women with thrombophilia and heparin-induced thrombocytopenia. Thromb Haemost. 2001 Suppl for XVIII ISTH: Abstr P2997.
  • 108 Houltz B, Gudnasson T, Tengborn L. Heparinbehandling gav trombocytopeni. Lakartidningen 1997; 94: 416-9.
  • 109 Huiet III F, Campbell CL, Grathwohl K. et al. Heparin-induced thrombocytopenia manifest as vena cava syndrome. South Med J 2000; 93: S41-2.
  • 110 Insler SR, Kraenzler EJ, Bartholomew JR. et al. Thrombosis during the use of heparinoid Organon 10172 in a patient with heparin-induced thrombocytopenia. Anaesth 1997; 86: 495-8.
  • 111 Jackson MR, Danby CA, Alving BM. Heparinoid anticoagulation and topical fibrin sealant in heparin-induced thrombocytopenia. Ann Thorac Surg 1997; 64: 1815-7.
  • 112 Jakobs D. Heparininduzierte Thrombozytopenie, Ventrikelthrombus und zerebrale Embolie im Verlauf eines akuten Myokardinfarkts. Med Klin 2001; 96: 101-4.
  • 113 Janssens U, Breithardt OA, Greinacher A. Successful thrombolysis of right atrial and ventricle thrombi encircling a temporary pacemaker lead in a patient with heparin-induced thrombocytopenia. Pacing Clin Electrophysiol 1999; 22: 678-81.
  • 114 Janssens U, Klues HG, Greinacher A. et al. Severe arterial and venous thromboses in a patient with heparin-induced thrombocytopenia type II. Intensive Care Med 1997; 23: 595-6.
  • 115 John G, Shehabi Y, Mudaliar Y. Use of a low molecular weight preparation of heparin - Org 10172 (Lomoparan) in the critically ill. Anaesth Intensive Care 1991; 19: 588-91.
  • 116 Kadidal W, Mayo DJ, Horne MK. Heparin-induced thrombocytopenia (HIT) due to heparin flushes: a report of three cases. L Int Med 1999; 246: 325-9.
  • 117 Kanagasabay RR, Unsworth-White MJ, Robinson G. et al. Cardiopulmonary bypass with danaparoid sodium and ancrod in heparin-induced thrombocytopenia. Ann Thorac Surg 1998; 66: 567-9.
  • 118 Keeling DM, Richards EM, Baglin TP. Platelet aggregation in response to four low molecular weight heparins and the heparinoid Org 10172 in patients with heparin-induced thrombocytopenia. Br J Haematol 1994; 86: 425-6.
  • 119 Keng B, Chong BH. Heparin-induced thrombocytopenia and thrombosis syndrome: in vivo cross-reactivity with danaparoid and successful treatment with r-hirudin. BJ Haematol 2001; 114: 394-6.
  • 120 Kiers L, Grigg LE, Cade JF. et al. Use of Org 10172 in the treatment of heparin-induced thrombocytopenia and thrombosis. Aust NZ J Med 1986; 16: 719.
  • 121 Kleinschmidt S, Seyfert UT. Heparin-associated thrombocytopenia (HAT) - still a diagnostic and therapeutical problem in clinical practice. Angiology 1995; 46: 37-44.
  • 122 Kleinschmidt S, Ziegenfuss T, Seyfert UT. et al. Septisch-toxisches Herz-Kreislauf-Versagen als Folge einer Heparin-induzierten Thrombozytopenie mit a“White Clot Syndromea”. Anaesth Intensivmed Notfallmed Schmerzther 1993; 28: 58-60.
  • 123 Klement D, Rammos S, van Kries R. et al. Heparin as a cause of thrombus progression. Eur J Pediatr 1996; 155: 11-4.
  • 124 Klenner AF, Lubenow N, Raschke R. et al. Heparin-induced thrombocytopenia in children. Thromb Haemost 2004; 91: 719-24.
  • 125 Kodityal S, Manhas AH, Udden M. et al. Danaparoid for heparin-induced thrombocytopenia: an analysis of treatment failures. Eur J Haematol 2003; 109-13.
  • 126 Kollig E, Maöllenhoff G, Wick M. et al. Wertigkeit der lokoregionalen Fibrinolyse von arteriellen Verschlaüssen bei Heparin-induzierter Thrombozytopenie. Gefasschirurgie 1998; 03: 212-7.
  • 127 Kollig E, Senkal M, Hentsch S. et al. Heparin-induced thrombocytopenia (HIT) during continuous veno-venous haemofiltration. Acta Anaesth Scand. 1997 41. 354, Abstr 096.
  • 128 Krenzien J, Gussmann A. Die Heparininduzierte Thrombopenie: Beobachtungen im eigenen Kranrengut. Zentralbl Chir 1999; 124: 230-3.
  • 129 Kuhn B. Heparin-induzierte Thrombozytopenie- eine ernstzunehmende Komplikation im Rahmen einer Heparin Therapie. Unfallchirurg 1997; 100: 646-51.
  • 130 Lam F, Hussein S, Li P. Case Reports: Limb loss following the use of heparin. J Bone Joint Surg 2001; 83-B: 588-9.
  • 131 Lamriben L, Tiberghien F, Delacour JL. et al. Intaéraêt de la’Orgaran en haémodialyse au cours da’une thrombopaéniea la’haéparine. Presse Maéd 1996; 25: 1303.
  • 132 Langenfeld H. Heparin-induzierte Thrombopenie vom Typ II bei einem Patienten mit schwerer Grundkrankheit. Haemostasiologie 2001; 21: 186-8.
  • 133 Langenfeld H. Heparin-induzierte Thrombopenie - Ein fast fataler Verlauf bei einem Patienten. Anasthesiol Intensivmed 2000; 41: 542-4.
  • 134 Larson L, Helms E, Garcia M. et al. Heparin-induced thrombocytopenia and thrombosis. Lab Med 1999; 30: 642-5.
  • 135 Lemesle FG, Mebroukine L, Ermacora P. et al. Thrombose, thrombopaénie sous HBPM et daélivrance. Presse Maéd 1998; 27: 19.
  • 136 Lillo-LeLouet A, Lasne D, Chamoun K. et al. Heparin-induced thrombocytopenia (HIT) revisited. Therapie 1998; 53: 177.
  • 137 Lindhoff-Last E, Betz C, Bauersachs R. Use ofa low molecular weight heparinoid (danaparoid sodium) for continuous renal replacement therapy in intensive care patients. Clin Appl Thromb Hemost 2001; 07: 300-4.
  • 138 Lindhoff-Last E, Bauersachs R. Heparin-induced thrombocytopenia: alternative anticoagulation in pregnancy and lactation. Seminars Thromb Haemost 2002; 28: 439-45.
  • 139 Lischetski G, Dittrich K, Topf H-G. et al. Pediatric heparin-induced thrombocytopenia type II on dialysis. Haemostaseologie. 2004 24. A48, Abstr P38.
  • 140 Lubenow N, Selleng S, Eichler P. et al. Cardiopulmonary bypass in patients with a history of heparin-induced thrombocytopenia: heparin re-exposure and peri-operative use of danaparoid, lepirudin and argatroban. Ann Hematol. 2001 80. (Suppl 1): A44, Abstr 163.
  • 141 Lubenow N, Eichler P, Albrecht D. et al. Very low platelet counts in post-transfusion purpura falsely diagnosed as heparin-induced thrombocytopenia: report of four cases and review of the literature. Thromb Res 2000; 100: 115-25.
  • 142 Macchi L, Sarfati R, Guicheteau M. et al. Thromboembolic prophylaxis with danaparoid (Orgarana®) in a high thrombosis risk pregnant woman with a history of heparin-induced thrombocytopenia (HIT) and Widala’s disease. Clin Appl Thromb Haemost 2000; 06: 187-9 [and as abstract in Thromb Haemost 1999; 82 (Suppl)]..
  • 143 Mahmmod N, Hustinx WNM. Skin necrosis distant to the site of injection of low molecular weight heparin (LMWH) in association with heparin-induced thrombocytopenia (HITT). Neth J Med. 2002 60. 81 Abstr 76.
  • 144 Mahul Ph, Raynaud Favre JP. et al. Thrombopaénie a la’haéparine: sous hemodialyse en reanimation: utilisation da’un haéparinoaïde de bas poids moleculaire Ia’Org 10172 (Orgarana®). Ann Fr Anesth Reanim 1995; 14: 29-32.
  • 145 Maistre de. 2001 Organon France marketing document..
  • 146 Maitra RT, Scheffold N, Cyran J. Heparin-induzierte Thrombozytopenie Typ II als schwerwiegende Komplikation in der Intensivmedizin. Intensivmed Notfallmed 1997; 34: 797-802.
  • 147 Mar AWY, Dixon B, Ibrahim K. et al. Skin necrosis following subcutaneous heparin injection. Aust J Dermatol 1995; 36: 201-3.
  • 148 Meer ZF, Morgan S, Belli AM. Case of the month: Dona’t bea clot. BJ Radiol 2001; 74: 877-8.
  • 149 Mims MP, Manian P, Rice L. Acute cardiorespiratory collapse from heparin: A consequence of heparininduced thrombocytopenia. Blood. 2002 100. (Suppl): Abstr 81b.
  • 150 Moonen M, Rorive G. Low molecular weight heparinoid Org 10172 (danaparoid) during continuous veno-venous haemofiltration in patients with heparininduced thrombocytopenia. Nephrol Dial Transplant 1997; 12: A169.
  • 151 Morewood GH. Uncomplicated heparinization for cardiopulmonary bypass in a patient with antiheparin antibodies. J Cardiothorac Vasc Anesth 2000; 14: 309-11.
  • 152 Morsdorf S, Pistorius C, Orthleb R. et al. Late onset of heparin-induced thrombocytopenia with recurrent arterial thromboses and amputation. Dtsch med Wschr 1999; 124: 1271-4.
  • 153 Muhm M, Claeys L, Huk I. et al. Thromboembolic complication ina patient with heparin-induced thrombocytopenia (HIT) showing cross-reactivity to a low molecular weight heparin-treatment with Org 10172 (Lomoparan). Wien Klin Wschr 1997; 109: 128-31.
  • 154 Neuhaus TJ, Goetschel P, Schmugge M. et al. Heparin-induced thrombocytopenia type II in hemodialysis: switch to danaparoid. Pediatr Nephrol 2000; 14: 713-6.
  • 155 Newall F, Barnes C, Ignjatovic V. et al. Heparininduced thrombocytopenia in children. J Paediatr Child Health 2003; 39: 289-92.
  • 156 Newman PM, Swanson RL, Chong BH. Heparininduced thrombocytopenia: IgG binding to PF4 heparin complexes in the fluid phase and cross-reactivity with low molecular weight heparin and heparinoid. Thromb Haemost 1998; 80: 292-7.
  • 157 Neyns B, Hubloue I, Kemp H von. et al. Unusual presentation of heparin-induced thrombocytopenia in a patient with inherited activated Protein C resistance. Acta Clin Belg 1998; 53: 293-4.
  • 158 Ng T, Tillyer ML. Warfarin induced skin necrosis associated with factor V Leiden and proteinS deficiency. Clin Lab Haem 2001; 23: 261-4.
  • 159 Nguyen TN, Gal P, Ransom JL. et al. Lepirudin use in a neonate with heparin-induced thrombocytopenia. Ann Pharmacother 2003; 37: 229-33.
  • 160 Oberst M, Vierling P, Thielemann F. Heparinassoziierte thrombocytopenie (HAT) Typ II Eine unterschatzte Komplikation der Thromboembolieprophylaxe mit Heparin. Chirurg 1998; 69: 198-203.
  • 161 Olin DA, Urdaneta F, Lobato EB. Use of danaparoid during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia. J Cardiothorac Vasc Anesth 2000; 14: 707-9.
  • 162 Olivier M, de Pina J-J, Pollet L. et al. Thrombopaénie induit par la’haéparine: aà propos da’un cas. Rev Francaise Lab 2000; 323: 75-7.
  • 163 Ortel TL, Gockerman JP, Califf RM. Parenteral anticoagulation with the heparinoid Lomoparan (Org 10172) in patients with heparin-induced thrombocytopenia and thrombosis. Thromb Haemost 1992; 67: 292-6 [previous abstract in Blood 1989; 74 (Suppl 1): 136a Abstr 502]..
  • 164 Pamboukian SV, Ignaszewski AP, Ross HJ. Management strategies for heparin-induced thrombocytopenia in heart transplant candidates: case report and review of literature. J Heart Lung Transplant 2000; 19: 810-4.
  • 165 Parney IF, Steinke DE. Heparin-induced thrombocytopenia and thrombosis following subarachnoid haemorrhage. J Neurosurg 2000; 93: 136-9.
  • 166 Perdu D, Lavaud F, Salmon V. et al. Vascular purpura induced by dalteparin. Rev Fr Allergol Immunol Clin 1999; 39: 564-6.
  • 167 Perry SL, O, Shea SI, Ortel TL. Management of lepirudin therapy for a patient with antiphospholipid syndrome using the blood ecarin clot time and activated partial thromboplastin time. Blood Coag Fibrinolysis 2003; 14: 601-4.
  • 168 Peters U, Egbring R, Fuchs G. et al. Aktivierung des Gerinnungs-Fibrinolyseund Endothelzellsystems bei vier Patienten mit Heparin-induziierter Thrombozytopenie (HAT II). Haemostasiologie 1995; 15: 127-31.
  • 169 Pfeiffer G, Eberhardt J, Hamann R. White Clot Syndrome bei heparin-induzierter thrombozytopenie Typ II mit Kreutzreaktion gegen danaparoid-Na (Orgarana®). Gefaässchirurgie 2000; 05: 125-9.
  • 170 Philipp A, Foltan M, Geitl Met al. Intervenionelle extrakorporale Lungunterstaützung (ILA) mittels arterio-venosem Shunt und einem neu entwickelten Low Resistance Lung Assist Device (LAD). Kardiotechnik 2003; 01: 7-13.
  • 171 Pineau E, Le Bret E, Folliguet T. et al. Utilisation de la’Orgarana®, heparinoaïde de synthaèse, lors de deux circulations extracorporelles, chez un maême patient allergique a la’haéparine. Arch Mal Couer 2001; 94: 144-7.
  • 172 Piovella F, Serafini S, Barzaghi N. et al. The combined use of Iloprost with danaparoid in the surgical management of a patient with chronic thrombo-embolic pulmonary hypertension and heparin-induced thrombocytopenia. Blood 1998; 92 (Suppl. 01) 124B-125B Abstr 3509..
  • 173 Pizzolo F, Girelli D, Olivieri O. Extensive lifethreatening thrombosis in a patient with heparin-induced thrombocytopenia and factor V Leiden mutation. Haematologica 2001; 86: 1008.
  • 174 Plassat R, Cognet F, Ternisien C. et al. Heparin induced thrombocytopenia: Case report and literature review. Ann Readaptation Med Physique 2002; 45: 216-23.
  • 175 Pohl C, Klockgether T, Greinacher A. et al. Neurological complications in heparin-induced thrombocytopenia. Lancet 1999; 353: 1678-9.
  • 176 Porzelt C, Drummer B, Hoffman A. Thromboseprophylaxe in der Schwangerschaft nach Polytraumatisierung mit Splenektomie und Immobilisation bei hepariniduzierter a“relativera” Thrombozytopenie Typ II. Geburtsh Frauenheilk 2002; 62: 784-6.
  • 177 Potger KC. Use of Orgaran as an alternative to heparin during CPB. Internet slides. 2004 Was available at Www. perfusion. com. au
  • 178 Pouplard C, Forisser JF, Delahousse B. et al. Severe heparin induced thrombocytopenia with thrombosis under low molecular weight heparin treatment (tinzaparin): three case reports. Thromb Haemost. 1999 82. (Suppl): 134, Abstr 416.
  • 179 Radke St, Schwaberg M, Storm G. et al. Das White Clot Syndrom. Zentralbl Chir 1998; 123: 573-8.
  • 180 Ramakrishna R, Manoharan A, Kwan YL. et al. Heparin-induced thrombocytopenia: cross reactivity between standard heparin, low molecular weight heparin, dalteparin (Fragmin), and heparinoid, danaparoid (Orgarana®). BJ Haematol 1995; 91: 736-8.
  • 181 Ranze O, Eichner A, Lubenow N. et al. The use of low molecular weight heparins in heparin-induced thrombocytopenia (HIT):a cohort study. Ann Hematol 2000; 79 (Suppl. 01) A93.
  • 182 Ranze O, Ranze P, Magnani H. et al. Heparin-induced thrombocytopenia in paediatric patients - a review of the literature anda new case treated with danaparoid sodium. Eur J Paediatr 199 158 (Suppl. 03) S130-133.
  • 183 Rice L, Attisha WK, Drexler A. et al. Delayed onset heparin-induced thrombocytopenia. Ann Int Med 2002; 136: 210-5.
  • 184 Robitaille D, Carrier M, Cartier R. et al. Successful management strategy for mechanical assistance and heart transplantation in patients suffering from heparin-induced thrombocytopenia Type II. J Heart Lung Transplant 2001; 20: 1237-40.
  • 185 Roe SD, Cassidy MJD, Haynes AP. Heparin-induced thrombocytopenia (HIT) and thrombosis in a haemodialysis-dependent patient with systemic vasculitis. Nephrol Dial Transplant 1998; 14: 3226-9.
  • 186 Rondeau M, Weber JC, Haffner C. et al. HELLP syndrome, catastrophic antiphospholipid syndrome or heparin-induced thrombocytopenia?. J Autoimmun. 2000 15. A68, Abstr P147.
  • 187 Rosel T, Druschkhy KF, Greinacher A. Complications, diagnosis and therapy of heparin-induced thrombocytopenia (HIT) Type II. Aktuelle Neurol 1999; 26: 25-30.
  • 188 Rowlings PA, Mansberg R, Rozenberg MC. et al. The use of a low molecular weight heparinoid (Org 10172) for extracorporeal procedures in patients with heparin dependent thrombocytopenia and thrombosis. Aust NZ J Med 1991; 21: 52-4 [and as abstract Aust NZ J Med 1990; 20 (Suppl 1): 401]..
  • 189 Salmi L, Leroy-Matheron C, LeBesnerais P. et al. Circulation extracorporelle sous danaparoaïde sodique pour remplacement valvulaire au cours da’une thrombopaénie induite par la’haéparine de Type II. Ann Fr Anesth Reanim 2001; 20: 799-802.
  • 190 Sauer M, Gruhn B, Fuchs D. et al. Heparin-induzierten Thrombozytopenie Typ II im Rahmen einer Hochdosis-Chemotherapie mit anschliessender Stammzellrescue. Klin Paädiatr 1998; 210: 102-5.
  • 191 Savoia H, Oa’Malley C, Grigg A. et al. Haematological aspects of heparin-induced thrombocytopenia (HITS) and the incidence of cross-reactive platelet aggregation with low molecular weight heparin and Organon 10172: the Royal Melbourne Hospital experience. Abstract Austral NZ J Med 1993; 23: 120.
  • 192 Saxon BR, Black MD, Edgell D. et al. Paediatric heparin-induced thrombocytopenia: management with danaparoid (Orgarana®). Ann Thorac Surg 1999; 68: 1076-8.
  • 193 Scheffler E, Aulmann M, Remppis A. et al. Erfolgreiche Anwedung eines Heparinoids (danaparoidnatrium) wegen Heparin-induzierter Thrombozytopenie Typ II bei Aortenklappenreoperation. Z Kardiol 1995; 84: 565-8 Erratum:Z Kardiol 1996; 85: 149.
  • 194 Schenk JF, Maösdorf S, Kroll H. et al. Prophylactic and therapeutic use of danaparoid (Orgarana®) in high risk patients-a prospective study. Ann Haematol. 2000 79. (Suppl 1): A89, Abstr P185.
  • 195 Schiffmann H, Unterhalt M, Harms K. et al. Erfolgreiche Behandlung einer Heparin-induzierten Thrombopenie Typ II im Kindesalter mit rekombinantem Hirudin. Monatsschr Kinderheilkd 1997; 145: 606-12.
  • 196 Schindewolf M, Mosch G, Bauersachs RM. et al. Safe anticoagulation with danaparoid in pregnancy and lactation. Thromb Haemost. 200492: 211..
  • 197 Schneider T, Heuer B, Deller A. et al. Continuous filtration with r-hirudin (Lepirudin) as anticoagulant in a patient with heparin-induced thrombocytopenia. Wien Klin Wochenschr 2000; 112: 552-5.
  • 198 Schmal KS, Ganjoo AK, Harloff MG. Danaparoid (Org 10172) for cardiopulmonary bypass in heparin-induced thrombocytopenia: role of adjunctive plasmapheresis. J Cardiothorac Vasc Anesth 1997; 11: 262-3.
  • 199 Schraöder A, Scherlitzky L, Budde U. et al. Recent aspects in the diagnosis and therapy of heparin-induced thrombocytopenia type II with thrombosis or haemorrhagic complications. Zentralbl Chir 1994; 119 (Suppl. 01) 151-3.
  • 200 Serafini S, Barone M, Beltrametti C. et al. Extracorporeal circulation and heparin-induced thrombocytopenia: combined use of Iloprost and danaparoid in the surgical management of chronic thromboembolic pulmonary hypertension Abstract. Thromb Haemost 1999; 91 (Suppl. 01) S127-8.
  • 201 Sharma S, Newman M, Gibbs N. et al. Cardiopulmonary bypass using Lomoparan: monitoring of anticoagulation using anti-Xa levels and thromboelastography. Aust NZ J Surg 1997; 67: 392-4.
  • 202 Shlebak AA, Lennox A, Smout J. et al. Anticoagulant induced skin necrosis: association with heparin-induced thrombocytopenia and acquired protein S deficiency due to anti-phospholipid syndrome. Br J Haematol 2002; 117 (Suppl. 01) 26-7 Abstr 73..
  • 203 Smoot EC, Marx A, Weiman D. et al. Recognition, diagnosis and management of heparin-induced thrombocytopenia and thrombosis. Plastic Reconstructive Surg 1999; 103: 559-65.
  • 204 Sodian R, Loebe M, Gorman KF. et al. Heparininduced thrombocytopenia: experiences in 12 heart surgery patients. ASAIOJ 1997; 32: M430-3.
  • 205 Sodian R, Loebe M, Hofmeister J. et al. Heparininduzierte Thrombozytopenia vom Typ II bei einem Patienten mit biventrikulaärem Unterstaützsungssystem. Z Herz Thorax Gefaässchir 1998; 12: 140-3.
  • 206 Staöckli TC, Walther A, Gaörres G. et al. Heparininduced thrombocytopenia and thrombosis. Schweiz Med Wschr 1996; 126: 483-8.
  • 207 Strauss R, Wehler M, Mehler K. et al. Thrombocytopenia in patients in the medical intensive care unit: bleeding prevalence, transfusion requirements and outcome. Crit Care Med 2002; 30: 1765-71.
  • 208 Tardy B, Tardy-Poncet B, Viallon A. et al. Fatal danaparoid-sodium induced thrombocytopenia and arterial thromboses. Thromb Haemost 1998; 80: 530.
  • 209 Tardy-Poncet B, Tardy B, Reynaud J. et al. Efficacy and safety of danaparoid sodium (Org 10172) in critically ill patients with heparin-associated thrombocytopenia. Chest 1999; 115: 1616-20.
  • 210 Tardy-Poncet B, Reynaud J, Tardy B. et al. Thrombopenie induit par la’heparine: traitement par la’Org 10172. Presse Maéd 1996; 25: 751-5.
  • 211 Tardy-Poncet B, Reynaud J, Tardy B. et al. Efficacy and safety of Orgaran anticoagulation in patients with heparin-induced thrombocytopenia. Thromb Haemost 1995; 73: 1323 Abstr 1627..
  • 212 Theuerkauf I, Lickfelt L, Harbrecht U. et al. Segmental hepatic vein thrombosis associated with heparin-induced thrombocytopenia II. Virchows Arch 2000; 436: 88-91.
  • 213 Tholl U, Greinacher A, Overdick K. et al. Lifethreatening anaphylactic reaction following parathyroidectomy in a dialysis patient with heparin-induced thrombocytopenia. Nephrol Dial Transplant 1997; 12: 2750-5.
  • 214 Tilgner J, Woydt M, Bock M. et al. Late post-operative haemorrhage in a female patient after surgery on an orbital tumor due to heparin-induced thrombocytopenia (HIT). Poster presented at the 54th Annual Meeting of the Deutsche Gesellschaft faür Neurochirurgie, Saarbraücken 25-28. May. 2003
  • 215 Tossios P, Krian A. Heparin-induced thrombocytopenia and associated complications after routine cardiac surgery. Z Cardiol. 2000 89. (Suppl 6): 42, Abstr 8.
  • 216 Tossios P, Atmaca N, Evagelopoulos N. et al. Experiences with danaparoid (Orgarana®) for cardiopulmonary bypass in open heart surgery: report on 5 cases. Ann Haematol. 1999 78. (Suppl 1): A50.
  • 217 Tran HA, Gan TE. Thrombocytopenia with idiopathic thrombocytopenic purpura (ITP) and heparininduced thrombocytopenia (HIT): double jeopardy successfully treated with cyclophosphamide and ancrod. Blood. 1999 94. (Suppl 1) 113b Abstr 3670.
  • 218 Vaal K, Winkler M, Rath W. Severe heparin-induced thrombocytopenia (HIT II syndrome) with sinus venosus thrombosis after female breast surgery - successful treatment with recombinant hirudin. Geburtsh Frauenheilk 1998; 58: 614-7.
  • 219 Velten U, Maücke Th. Heparin-induzierte thrombozytopenie. Anaesthesiol Intensivmed 1996; 02: 76-80.
  • 220 Warkentin TE, Kelton JG. Delayed onset heparin induced thrombocytopenia and thrombosis. Ann Intern Med 2001; 135: 502-6.
  • 221 Weigel B, Laskey A, Krishnamurti L. et al. Danaparoid (Orgaran) anticoagulation of paediatric patients with heparin-induced thrombocytopenia (HIT). J Paed Haematol Oncol 2003; 21: 327 Abstr 432..
  • 222 Wenzl ME, Leffringhausen W, Scherlitzky L. Loss of extremities caused by heparin-induced thrombocytopenia. Unfallchirurg 1996; 99: 607-11.
  • 223 Wester JPJ, Stolk M, Geers ABM. et al. Danaparoid sodium in CAVHD in seriously ill patients with heparin-induced thrombocytopenia. Neth Med J 2000; 56: A44.
  • 224 Wester JPJ, Haas FJLM, Biesma DH. et al. Thrombosis and haemorrhage in heparin-induced thrombocytopenia in seriously ill patients. Intensive Care Med 2004; 30: 1927-34.
  • 225 Westphal K, Martens S, Strouhal S. et al. Heparininduced thrombocytopenia type II: peri-operative management using danaparoid in a coronary artery bypass patient with renal failure. Thorac Cardiovasc Surg 1997; 45: 318-20.
  • 226 Weyrich P, Balletshofer B, Hoeft S. et al. Acute adrenocortical insufficiency due to heparin-induced thrombocytopenia with subsequent bilateral haemorrhagic infarction of the adrenal glands. VASA 2001; 30: 285-8.
  • 227 Wilhelm MJ, Schmid C, Kececioglu D. et al. Cardiopulmonary bypass in patients with heparin-induced thrombocytopenia using Org 10172. Ann Thorac Surg 1996; 61: 920-4.
  • 228 Wilson M, Forsyth C, McGahan T. et al. Management of acute vascular graft thrombosis associated with HIT syndrome. Aust NZ J Surg 1997; 67: 302-3.
  • 229 Wiltink EHH, Ramjankhan FZ, Haas FJLM. et al. Heparin-induced thrombocytopenia and heparin-induced thrombosis Treatment with danaparoid and platelet-activation inhibitors. Ziekenhuisfarmacie 1996; 12: 225-7.
  • 230 WooYl Allard S, Cohen H. et al. Danaparoid prophylaxis in pregnant women with heparin-induced thrombocytopenia. BJOG 2002; 109: 466-8.
  • 231 Zimmermann-Schroeder J, Castedello Th, Bahmer FA. Heparin-induzierte Nekrosen bei dialysepflichtiger Niereninsuffizienz. Z Hautkrankheiten 1998; Ha+G5 (73) 273-8.
  • 232 Zaöhrer B, Zenz W, Rettenbacher A. et al. Danaparoid sodium (Orgarana®) in four children with heparininduced thrombocytopenia type II. Acta Paediatrica 2001; 90: 765-71.
  • 233 Armager S, Ferrier-le-Bouaëdec M-C, Mansard Set al. Delayed hypersensitivity skin reactions to heparins and heparinoids. Rev Fr Allerg Immunol Clin 2002; 43: 170-4.
  • 234 Andreescu ACM, Possidente C, Hsieh M. et al. Evaluation of a pharmacy-based surveillance program for heparin-induced thrombocytopenia. Pharmacother 2000; 20: 974-80.
  • 235 Boon DMS, Michiels JJ, Tanghe HLJ. et al. Heparin-induced thrombocytopenia with multiple cerebral infarctions simulating thrombotic thrombocytopenic purpura. Angiology 1996; 47: 11.
  • 236 Chong BH, Mansberg R. Org 10172 in heparininduced thrombocytopenia (HIT). Aust NZ J Med 1991; 21: 949.
  • 237 Chong BH, Jacques T. Haemofiltration/haemodialysis in patients with heparin-associated thrombocytopenia. Intensive Care Med 1991; 17: 437.
  • 238 Deryck YL, Schepp RM, Krugten van RJ. et al. Heparinoid Org 10172 anticoagulation for cardiopulmonary by-pass: a case report. J Cardiothorac Anaesth 1990; 46 (Suppl. 03) P40.
  • 239 Doherty DC, Ortel TL, Bruijn N de. et al. a“Heparin freea” cardiopulmonary bypass: first reported use of heparinoid (Org 10172) to provide anticoagulation for cardiopulmonary bypass. Anesth 1990; 73: 562-5.
  • 240 Elalamy I, Page Y, Viallon A. et al. The diagnosis and development of heparin-induced thrombocytopenia Clinical and biological aspects. Revue des Maladies Respiratoires 1999; 16: 961-74.
  • 241 Eps van RS, Wester JPJ, Ruiter de FE. et al. The incidence of heparin-induced thrombocytopenia in critically ill patients with the. Thromb Haemost. 2001 available on CD-ROM.
  • 242 Eps van RS, Wester JPJ, Ruiter de FE. et al. Danaparoid sodium in continuous venovenous hemofiltration in patients with multiple organ dysfunction syndrome. Neth J Med 2000; 56: A40-41.
  • 243 Erdlenbruch W, Stephan B, Moersdorf S. et al. The dosage of danaparoid influences significantly the increase of platelets in patients with HIT II. Ann Hematol. 2001 80. (Suppl 1): A16, Abstr 51.
  • 244 Farag SF, Savoia H, Oa’Malley C. et al. Lack of in vitro cross reactivity pedicts saftey of low molecular weight heparins in heparin-induced thrombocytopenia. Aust NZ J Med 1996; 26: 276.
  • 245 Ganzer D, Gutezeit A, Mayer G. et al. Thromboembolism prophylaxis as a cause of thromboembolic complications An investigation into the incidence of heparin-induced thrombocytopenia (HIT) type II. Z Orthop Grenzg 1997; 90: 543-9.
  • 246 Greinacher A, Michels I, Mueller-Eckhardt C. Heparin-assoziierteThrombozytopenie (HAT): Erfolgreiche Therapie von Patienten nach prospektiver Auswahl eines kompatiblen Heparinoids mit dem Heparin-induzierten Plattchenaktivierungs-(HIPA)-Test. Beitr Infusionsther 1992; 30: 408-12.
  • 247 Harbrecht UM, Pohl C, Greinacher A. et al. Neurological complications in patients with immune-mediated heparin-induced thrombocytopenia. 1999 Abstract.
  • 248 Horellou MH, Conard J, Achkar A. et al. Treatment of thrombosis with low molecular weight heparins during 15 pregnancies in 14 women. Thromb Haemost. 1997 77. (Suppl): 733 Abstr PS-2992.
  • 249 Kleinschmidt S, Seyfert UT. A diagnostic and therapeutic approach to heparin-associated thrombocytopenia. Clin Hemorheology 1994; 14: 137-40.
  • 250 Mahlfield K, Bock M, Franke J. et al. The importance and incidence of heparin-induced thrombocytopenia (HIT) tpe II A prospective study. Zentrbl Chir 2001; 126: 39-43.
  • 251 Mahul Ph, Raynaud J, Jospe R. et al. Thrombopaénie a la’haéparine: utilisation da’un haéparinoaïde de bas poids moleculaire, la’Org 10172 (Lomoparana®) Ann Fr Anesth Reanim. 1993; 12 (Suppl) R191.
  • 252 Marshall LR, Cannell PK, Herrmann RP. Successful use of the APTT in monitoring of the heparinoid Organon 10172 in a case of HITS requiring open heart surgery. Thromb Haemost 1992; 67: 587.
  • 253 Monagle PT, Barnes C, Newall F. et al. Twelve months experience with a paediatric thrombosis program. Blood. 2001 98. 95b, Abstr 4016.
  • 254 Pouplard C, Amiral J, Borg Y. et al. Differences in specificity of heparin-dependent antibodies developed in heparin-induced thrombocytopenia and consequences on cross-reactivity with danaparoid sodium. BJ Haematol 1997; 99: 273-80.
  • 255 Rice L, Attisha WK, Drexler A, Francis JL. Delayed onset heparin-induced thrombocytopenia. Ann Int Med 2002; 136: 210-5.
  • 256 Saint-Maurice O, Petrie J, Bourel P. et al. Danaparoid et chirurgie cardiaque en cas da’allergie a la’heparine. Internet publication. Danaparoid website. 2002 No longer available.
  • 257 Tardy-Poncet B. French experience in the use of Orgarana® as an alternative antithrombotic treatment for patients with heparin-induced thrombocytopenia. 16th ISTH:Abstract/Poster No PS-1825 Thromb Haemost. 1997; 77 (Suppl. 01) 447.
  • 258 Tardy-Poncet B, Mahul P, Beraud A-M. et al. Failure of Orgaran therapy in a patient with previous heparin-induced thrombocytopenia syndrome. B J Haematol 1995; 90: 969-73.
  • 259 Tardy-Poncet B. Efficacy and safety of Orgarana® anticoagulation in patients with heparin-induced thrombocytopenia. Thromb Haemost 1995; 73: 1627.
  • 260 Tardy-Poncet B, Tardy B. Viallon, et al. Lower limb veins must be systematically explored in patients with isolated heparin-induced thrombocytopenia. Thromb Haemost. 1999 82. (Suppl) Abstr 804.
  • 261 Warkentin TE. Danaparoid sodium (Orgarana®) for the treatment of heparin-induced thrombocytopenia (HIT) and thrombosis:effects on in vivo thrombin and cross-linked fibrin generation and evaluation of the clinical significance of in vitro cross-reactivity (XR) of danaparoid for HIT IgG. Blood. 1996 88. (Suppl 1) 626A Abstr 2493.
  • 262 Lindhoff-Last E, Kreutzenbeck H-J, Magnani HN. Treatment of 51 pregnancies with danaparoid because of heparin intolerance. Thromb Haemost 2005; 93: 63-9.
  • 263 Meuleman D. Danaparoid (Org 10172): Its pharmacological profile in experimental models. Haemostasis 1992; 22: 58-65.
  • 264 Smythe MA, Warkentin TE, Stephens JL. et al. Venous limb gangrene during overlapping therapy with warfarin and a direct thrombin inhibitor for immune heparin-induced thrombocytopenia. Am J Hematol 2004; 71: 50-2.
  • 265 Bartholomew JR. Transition to an oral anticoagulant in patients with heparin-induced thrombocytopenia. Chest 2005; 127: 27-34.
  • 266 Lubenow N, Warkentin TE, Greinacher A. et al. A systematic evaluation of treatment outcomes for heparin-induced thrombocytopenia in patients receiving danaparoid, ancrod and/or coumarin explains the rapid shift in clinical practice during the 1990s. Thromb Res 2005; 117: 507-15.
  • 267 Greinacher A, Warkentin TE. Treatment of heparin-induced thrombocytopenia: an overview. In: Heparin-Induced thrombocytopenia. 3rd Edition. Ed. Warkentin TE, Greinacher A; Marcel Dekker Inc: 2004: 335-70.
  • 268 Shalansky SJ, Verma AK, Levine M. Factors to consider before discontinuing heparin in patients who develop thrombocytopenia. Pharmacotherapy 1999; 19: 1011-2.
  • 269 Warkentin TE, Greinacher A. Laboratory testing for HIT. In: Heparin-Induced thrombocytopenia, 3rd Edition. Ed. Warkentin TE, Greinacher A; Marcel Dekker Inc: 2004: 313-70.
  • 270 Lubenov N, Eichler Albrecht D. et al. Very low platelet counts in post-transfusion purpura falsely diagnosed as heparin-induced thrombocytopenia: report of four cases and review of literature. Thromb Res 2000; 100: 115-25.
  • 271 Anon. Early awareness key to successful management of heparin-induced thrombocytopenia (HIT). Drug Ther Perspect 2001; 17: 8-12.
  • 272 Warkentin TE, Chong BH, Greinacher A. Heparin-induced thrombocytopenia: towards consensus. Thromb Haemost 1998; 79: 1-7.
  • 273 Kiefel V. Differential diagnosis of acute thrombocytopenia. In: Heparin-Induced thrombocytopenia. 3rd Edition. Ed. Warkentin TE, Greinacher A; Marcel Dekker Inc: 2004: 25-52.
  • 274 Warkentin TE. Pseudoheparin-induced thrombocytopenia. In: Heparin-Induced thrombocytopenia. 3rd Edition. Ed. Warkentin TE, Greinacher A; Marcel Dekker Inc; 2004: 313-34.
  • 275 Griffiths E, Dzik WH. Assays for heparin-induced thrombocytopenia. Transfusion Med 1997; 07: 1-11.
  • 276 Warkentin TE, Heddle NM. Laboratory diagnosis of immune heparin-induced thrombocytopenia. Current Hematology Reports 2003; 02: 148-57.
  • 277 Danhof M, de Boer A, Magnani HN. et al. Pharmacokinetic considerations on Orgaran (Org 10172) therapy. Haemost 1992; 22: 73-84.
  • 278 Carrier M, Robitaille D, Perrault LP. et al. Heparin versus danaparoid in off-pump coronary by-pass grafting: results of a prospective randomised clinical trial. J Thorac Cardiovasc Surg 2003; 125: 325-9.
  • 279 Warkentin TE, Dunn GL, Cybulsky IJ. Off-pump coronary artery bypass grafting for acute heparin-induced thrombocytopenia. Ann Thorac Surg 2001; 72: 1730-2.
  • 280 Greinacher A. Lepirudin in HIT treatment. In: Heparin-Induced thrombocytopenia. 3rd Edition. Ed. Warkentin TE, Greinacher A; Marcel Dekker Inc: 2004: 397-436.
  • 281 Lewis B, Hursting MJ. Argatroban therapy in heparin-induced thrombocytopenia. In: Heparin-Induced thrombocytopenia. 3rd Edition. Ed. Warkentin TE, Greinacher A; Marcel Dekker Inc: 2004: 437-74.
  • 282 Makhoul RG, Greenberg CS, McCann RL. Heparin associated thrombocytopenia and thrombosis: a serious problem and potential solution. J Vasc Surg 1999; 04: 522-8.
  • 283 Eichler P, Budde U, Haas S. et al. First workshop for the detection of heparin-induced antibodies: Validation of the heparin-induced platelet activation assay (HIPA) in comparison with a PF4/heparin ELISA. Thromb Haemost 1999; 81: 625-9.
  • 284 Blockmans D, Bounameux H, Vermylen J. et al. Heparin-induced thrombocytopenia platelet aggregation studies in the presence of heparin fractions or semi-synthetic analogues of various molecular weights and anticoagulant activities. Thromb Haemost 1986; 55: 90-3.
  • 285 Elalamy I, Lecrubier C. Potevin et al. Absence of in-vitro cross reaction of pentasaccharide with plasma heparin-dependent factor of twenty five patients with heparin-associated thrombocytopenia. Thromb Haemost 1995; 74: 1384-85.
  • 286 Harbrecht U, Unkrig CJ. Heparin-induced thrombocytopenia Type II: platelet aggregation studies with low molecular weight heparin and heparinoid Org 10172. Thromb Haemost 1991; 65: 1302.
  • 287 Kikta MJ, Keller MP, Humphrey PW. et al. Can low molecular weight heparins and heparinoids be safely given to patients with heparin-induced thrombocytopenia syndrome?. Surgery 1993; 114: 705-10.
  • 288 Kleinschmidt S, Seyfert UT. Heparin-associated thrombocytopenia (HAT) - still a diagnostic and therapeutic problem in clinical practice. Angiology 1995; 46: 37-44.
  • 289 Koster A, Kuppe H, Hetzer R. et al. Emergent cardiopulmonary bypass in five patients with heparin induced thrombocytopenia Type II employing recombinant hirudin. Anaesthesiology 1998; 89: 777-80.
  • 290 Kroll H, Jonas T, Kreiling S. Immunologic analysis of 4741 patients with clinically suspected heparin-induced thrombocytopenia. Ann Hematol. 2000 79. (Suppl 1): A88, Abstr 182.
  • 291 Schmidt S, Ludtke-Handjery A, Lottermoser KH. Die Heparin-assozierte Thrombozytopenie als Problem der Heparintherapie. Chirurg 1993; 64: 715-9.
  • 292 Tomer A, Masalunga C, Abshire TC. Determination of heparin-induced thrombocytopenia: a rapid flow cytometric assay for direct determination of antibody mediated platelet activation. Am J Hematol 1999; 61: 53-61.
  • 293 Vun CM, Evans S, Chong BH. Cross-reactivity study of low molecular weight heparins and heparinoid in heparin-induced thrombocytopenia. Thromb Res 1996; 81: 525-32.
  • 294 Walenga J, Silber I, Koza M. et al. Lack of heparin induced thrombocytopenia response with the use of the new antithrombotic agents. Blood. 1991 78. (Suppl 1): Abstr 569.
  • 295 Warkentin TE. Heparin-induced thrombocytopenia, Part 2: clinical course and treatment. J Crit Illness 2002; 17: 215-21.
  • 296 Figarella I, Barbaud A, Lecompte T. et al. Raéaction cutanaée da’hypersensibilitaé retardaée avec polysensibilisation aux haéparines et haéparinoaïdes. Ann Dermatol Venereol 2001; 128: 25-30.
  • 297 Grassegger A, Fritsch P, Reider N. Delayed-type hypersensitivity and cross-reactivity to heparins and heparinoids: a prospective study. Dermatol Surg 2001; 27: 47-52.
  • 298 Harenberg J, Huhle G, Wang L. et al. Association of heparin-induced skin lesions, intracutaneous tests and heparin-induced IgG. Allergy 1999; 54: 473-7.
  • 299 Koch P, Maüaßinger Rupp-John C, Uhl K. Delayedtype hypersensitivity skin reactions caused by subcutaneous unfractionated and low molecular weight heparins: tolerance of a new recombinant hirudin. J Am Acad Dermatol 2000; 42: 612-9.
  • 300 Wutschert R, Piletta P, Bounameaux H. Adverse skin reactions to low molecular weight heparins. Drug Safety 1999; 20: 515-25.
  • 301 Nicolie B, Bonneau J-C, Le Sellin J. et al. Hypersensibilite retardee aux heparines et heparinoides. Allergie et Immunologie 2002; 34: 47-50.
  • 302 Boehncke WH, Weber L, Gall H. Toleranz gegenaüber intravenaöser Applikation von Heparin und Heparinoid bei einer Patientin mit Typ-IV Allergie auf Heparine und Heparinoide. Allergologie 1996; 19: 95.
  • 303 Drew PJ, Smith MJ, Milling MAP. Heparin-induced skin necrosis and low molecular weight heparins. AnnRC Surg Engl 1999; 81: 266-9.