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Danaparoid

A Review of its Use in Thromboembolic and Coagulation Disorders

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Summary

Abstract

Danaparoid (danaparoid sodium) is a low molecular weight heparinoid which has undergone clinical study for use as continued anticoagulant therapy in patients with heparin-induced thrombocytopenia (HIT), for the prophylaxis and treatment of deep vein thrombosis (DVT), and for the treatment of disseminated intravascular coagulation (DIC).

A nonblind study in patients with HIT has reported that complete clinical resolution is significantly more likely in patients receiving danaparoid than in patients receiving dextran 70. In addition, retrospective analyses and non-comparative data support the use of danaparoid for continued anticoagulant therapy in patients with HIT.

Studies in patients undergoing hip surgery have shown that danaparoid significantly reduces the incidence of postoperative DVT compared with aspirin, warfarin, dextran 70 and heparin-dihydroergotamine, while additional data suggest no difference between danaparoid, enoxaparin and dalteparin. In patients undergoing abdominal or thoracic surgery for removal of a malignancy, danaparoid reduced the incidence of postoperative DVT compared with placebo, but showed no significant difference when compared with unfractionated heparin (UFH). Two studies have compared danaparoid with UFH in the prophylaxis of DVT following acute ischaemic stroke; twice daily danaparoid was significantly superior to UFH whereas there was no significant difference between a once-daily dosage and UFH. Danaparoid did not differ from UFH in terms of efficacy in the treatment of existing DVT. In all comparative studies examining the efficacy of danaparoid in the prophylaxis or treatment of DVT (versus warfarin, dextran 70, enoxaparin, dalteparin, aspirin, heparin-dihydroergotamine, UFH and placebo), the incidence of haemorrhagic complications did not differ between treatment groups.

In patients with DIC, 61.9% of those patients receiving danaparoid experienced either disappearance or reduction of symptoms of DIC whereas 62% of those receiving UFH showed either no change or aggravation of their symptoms. There was no significant difference between treatment groups in tolerability or overall improvement of DIC.

Conclusions: Danaparoid is an effective anticoagulant agent which has undergone clinical evaluation in a wide range of disease indications. Current guidelines support the use of danaparoid in prophylaxis of DVT following ischaemic stroke, and in patients who develop HIT. Danaparoid has shown efficacy in DIC, and for DVT prophylaxis in patients undergoing hip surgery although further data are required to establish the role of danaparoid in these indications. In particular, double-blind trials comparing danaparoid with such recommended therapies as the low molecular weight heparins will provide more definitive data on the place of danaparoid in the clinical management of these conditions and ultimately lead to improved patient outcomes.

Overview of Pharmacodynamic Properties

Danaparoid (danaparoid sodium) is a low molecular weight heparinoid, consisting of glycosaminoglycans, with a mean molecular mass of approximately 5500D. Its active components are heparan sulphate (≈84%), dermatan sulphate (≈12%) and chondroitin sulphates A and C (≈4%). Danaparoid catalyses the antithrombin-mediated inactivation of factor Xa leading to an inhibition of thrombin generation and ultimately thrombus formation. Danaparoid also weakly enhances antithrombin III and heparin cofactor II inactivation of factor IIa and has relatively little effect on platelet aggregation.

Overview of Pharmacokinetic Properties

There are no specific assays for determining the plasma concentrations of danaparoid and so pharmacokinetic measurements are based on the kinetics of its anticoagulant activities, primarily plasma antifactor Xa. The majority of data concerning danaparoid anticoagulant activities have been obtained following single-dose injections in healthy volunteers. The absolute bioavailability of danaparoid following subcutaneous injection approaches 100% and peak antifactor Xa activity occurs between 2 and 5 hours after administration. After intravenous administration, danaparoid has a mean distribution half-life of antifactor Xa activity of 2.34 hours. Renal excretion is the main route of elimination, accounting for up to 50% of the total plasma clearance of antifactor Xa activity. No clinically significant drug interactions have been reported between danaparoid and agents which act on platelet function or haemostasis. Oral chlorthalidone significantly increased the volume of distribution (Vd) of antifactor IIa activity, and decreased clearance (CL) and Vd of antifactor Xa activity. Digoxin significantly increased CL of antifactor Xa activity.

Therapeutic Use

Treatment of Heparin-induced Thrombocytopenia

A small nonblind prospective study has compared danaparoid with dextran 70 as anticoagulant therapy in patients with heparin-induced thrombocytopenia (HIT). Patients randomised to danaparoid received a bolus intravenous injection of 2400U, followed by continuous intravenous infusion. Dextran 70 was given as an intravenous infusion of 1L on day 1, followed by infusions of 0.5L daily for the next 4 days. All patients also received concomitant warfarin. Study drugs were started within 24 hours of stopping unfractionated heparin (UFH) and were continued for at least 72 hours. Thrombocytopenia resolved in 23 patients receiving danaparoid (92%) and 15 patients receiving dextran 70 (88%) and the mean time to resolution of HIT did not differ between treatments (6.7 vs 7.3 days). Complete clinical resolution of thromboembolic events and partial or complete clinical recovery was significantly more likely in patients receiving danaparoid than in those receiving dextran 70.

A retrospective analysis comparing patients receiving lepirudin as part of a formal clinical trial with patients receiving danaparoid in a general clinical setting has shown no significant difference between the treatments. In 730 patients with HIT receiving danaparoid in three noncomparative studies, thrombocytopenia persisted or appeared de novo in 6.1, 6.5 and 13.6% of patients. Several case reports and a series of 47 patients also document the successful use of danaparoid in the treatment of HIT in pregnant women, paediatric patients and patients undergoing cardiovascular surgery including cardiopulmonary bypass.

Prophylaxis and Treatment of Deep Vein Thrombosis

Six comparative studies have examined the use of danaparoid for the prophylaxis of deep vein thrombosis (DVT) in patients undergoing hip surgery (either fracture or hip replacement). Danaparoid was variously administered prior to surgery and then following surgery at a dosage of 750U subcutaneously twice daily. Two large, randomised studies showed that patients receiving danaparoid for 7 to 8 days following surgery developed significantly lower rates of DVT than patients receiving warfarin (patients with hip fracture 7 vs 21%; those with total hip replacement 14.6 vs 26.9%). Similarly, in a double-blind study in patients undergoing surgery for hip fracture, danaparoid was significantly more effective at reducing the incidence of DVT than aspirin (100mg twice daily) after treatment for 14 days following surgery (27.8 vs 44.3%). Randomised comparisons with dextran 70 and with heparin-dihydroergotamine (DHE) also suggest that danaparoid provides effective prophylaxis of DVT. The incidence of DVT in patients receiving danaparoid was significantly lower than in those receiving dextran 70 (10 vs 31%) or heparin-DHE(17 vs 33%). Finally, in a comparison of danaparoid with enoxaparin (40 mg/day subcutaneously) and dalteparin (5000 U/day subcutaneously) in patients undergoing surgery for hip fracture, there was no significant difference in the incidence of DVT between treatment groups (5.7 vs 15.4 vs 8.8%, respectively).

Danaparoid has also been compared with UFH for the prophylaxis of DVT in 490 patients undergoing surgery for suspected gastrointestinal malignancy or lung cancer. There was no statistically significant difference in the frequency of positive leg scan results between treatment groups (danaparoid 7.9 vs UFH 11.2%).

In two double-blind studies in patients with ischaemic stroke, no significant difference was observed between danaparoid (1250U once daily) and UFH (5000 U/day subcutaneously twice daily) in reducing the incidence of DVT (14.6 vs 19.8%) with treatment for a minimum of 9 days. However, in a separate study, danaparoid (750U twice daily) was significantly more effective than UFH (5000 U/day subcutaneously twice daily) in reducing the occurrence of DVT (9 vs 31%) when treatment was continued for 14 days. In a placebo-controlled, double-blind study, danaparoid (750U twice daily) significantly reduced the incidence of DVT compared with placebo (4 vs 28%).

The ‘Trial of ORG 10172 (danaparoid) in Acute Stroke Treatment’ (TOAST) was a multicentre, placebo-controlled study in 1275 patients with acute or progressing ischaemic stroke to assess the effect of danaparoid on neurological outcomes. There was no significant difference in the frequency of favourable outcome (assessed using the Glasgow Outcome Scale and Barthel Index) at 7 days or at 3 months. There was also no significant difference between treatment groups in the frequency of very favourable outcome at 3 months; however, after 7 days’ treatment, significantly more patients receiving danaparoid reported very favourable outcomes compared with those receiving placebo. The incidence of DVT during the 3-month follow-up was significantly lower in patients who received danaparoid than in patients who received placebo.

An assessor blind study has compared the efficacy of danaparoid with that of UFH for the treatment of venous thromboembolism in 188 patients. The frequency of recurrence or extension of DVT was significantly lower in patients receiving danaparoid 2000U subcutaneously twice daily (13%) than in those receiving UFH (28%) or in those receiving danaparoid 1250U subcutaneously twice daily (28%) when assessed after 5 to 8 days. Similar results were found 2 months after the initiation of study treatment.

Treatment of Disseminated Intravascular Coagulation

The use of danaparoid (1250U twice daily) in the treatment of disseminated intravascular coagulation (DIC) was examined in 85 patients in a randomised double-blind, double-dummy comparison with UFH (continuous intravenous infusion of 7 to 10 U/kg/h). There was no significant difference in the rate of change of the underlying condition between treatment groups after 5 days of treatment. Ten patients receiving danaparoid (23.3%) and 12 patients receiving UFH (28.6%) were considered to have an easing or recovery of their underlying condition. Similar numbers of patients in each group showed no change in (55.8 and 47.6%) or aggravation of (20.9 and 23.8%) the severity of their underlying condition. There was also no difference between treatment groups in DIC scores during the study. The only comparative study with danaparoid in the treatment of DIC has reported that 61.9% of patients receiving danaparoid experienced either disappearance or reduction of symptoms of DIC whereas 62% of patients receiving UFH showed either no change or aggravation of their symptoms.

Tolerability

Heparin-Induced Thrombocytopenia

A noncomparative study has reported that from a total of 667 patients who were receiving danaparoid for antithrombotic medication with associated HIT, 67 developed serious adverse events (including new or extension of thrombosis, skin rash, bleeding, and persistent of recurrent platelet count).

Indirect comparison of danaparoid and lepirudin suggests that significantly fewer patients receiving danaparoid developed a major bleeding event than patients receiving lepirudin (2.5 vs 10.4%). Finally, in a prospective nonblind comparative study, one patient receiving danaparoid and three receiving dextran 70 died of HIT-associated thrombosis.

Deep Vein Thrombosis

In 9 studies which evaluated the efficacy and tolerability of danaparoid in the prophylaxis of DVT following surgery, the incidence of haemorrhagic complications did not differ significantly between danaparoid and the comparator agent. Most studies showed no significant difference between danaparoid and the comparator agent regarding blood loss and transfusion requirements during surgery; however, one study reported that significantly fewer patients receiving danaparoid required a postoperative blood transfusion compared with those receiving dextran 70 and, in a second study, more patients receiving danaparoid required intraoperative blood transfusion compared to those receiving heparin-DHE. Blood loss and mortality were generally similar between treatment groups.

In the TOAST study, major bleeding events were significantly more frequent in patients receiving danaparoid during prophylaxis (7 days), within 10 days of starting therapy and throughout the 3-month period of observation than in those receiving placebo (p < 0.05 in all cases). In addition, serious brain bleeding during the initial 10 days of therapy, and minor bleeding during treatment and during the initial 10 days of therapy were also observed significantly more frequently in patients receiving danaparoid than in those receiving placebo (p < 0.05 in each case).

Five patients with ischaemic strokes from three studies developed major bleeding complications; three of these patients were receiving danaparoid, one was receiving UFH, and one placebo. One case of a fatal haemorrhagic transformation associated with danaparoid treatment was reported. In patients receiving danaparoid for treatment of DVT, major bleeding occurred in two patients receiving UFH and two receiving danaparoid.

Disseminated Intravascular Coagulation

Data from the only comparative study with danaparoid in the treatment of DIC suggests that there are no significant tolerability differences between danaparoid and UFH. Three patients receiving UFH and no patients receiving danaparoid experienced bleeding-related adverse events.

Dosage and Administration

Throughout Western Europe danaparoid is approved for the treatment of HIT. For continued anticoagulation in patients with HIT, danaparoid should be administered intravenously as abolus of 2500U (1250U if bodyweight is <55 kg, 3750U if >90kg) followed by a continuous intravenous infusion of 400 U/h for 2 hours, 300 U/h for the next 2 hours, then a maintenance infusion of 200 U/h for 5 days.

In the US, danaparoid has received regulatory approval for the prophylaxis of postoperative DVT in patients undergoing elective hip replacement. In Europe, it has received regulatory approval for the prophylaxis of DVT in patients undergoing general or orthopaedic surgery. For DVT prophylaxis, danaparoid should be administered by subcutaneous injection at a dose of 750U twice daily beginning 1 to 4 hours before surgery and then not sooner than 2 hours after surgery. Treatment duration should be 7 to 10 days, and up to 14 days where necessary.

In Japan, danaparoid has received regulatory approval for use in the treatment of DIC. The recommended normal adult dosage is 1250U twice daily via intravenous administration.

Patients with moderately or severely impaired kidney or liver function, or impaired haemostasis should exercise caution when taking danaparoid, as delayed excretion may lead to haemorrhage. Dosage should be reduced or intervals between dosages increased if serum creatinine levels are ≥2 g/L. In patients with severe renal damage, consideration should be given to suspending treatment. Breast-feeding mothers should only be given danaparoid if clearly required, and the tolerability of danaparoid in infants and paediatric patients has not been confirmed. Finally, danaparoid is contraindicated in patients with haemorrhage (or at risk of haemorrhage), requiring haemodialysis, with severe liver damage, with hypersensitivity to danaparoid, with HIT who display cross-reactivity between danaparoid and HIT antibodies, with diabetic retinopathy and in those who have recently undergone brain, spinal or eye surgery.

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References

  1. ORGARAN (danaparoid sodium). Japanese Package Insert. 2000. Organon Ltd. The Netherlands.

  2. Wilde MI, Markham A. Danaparoid. A review of its pharmacology and clinical use in the management of heparin-induced thrombocytopenia. Drugs 1997 Dec; 54(6): 903–24

    CAS  Google Scholar 

  3. Fujishima Y, Yokota K, Sukamoto T. The effect of danaparoid sodium (danaparoid) on endotoxin-induced experimental disseminated intravascular coagulation (DIC) in rats. Thromb Res 1998 Sep 1; 91(5): 221–7

    Article  PubMed  CAS  Google Scholar 

  4. Miyake Y, Yokota K, Fujishima Y, et al. The effects of danaparoid, dalteparin and heparin on tissue factor- induced experimental disseminated intravascular coagulation and bleeding time in the rat. Blood Coagul Fibrinolysis 2001 Jul; 12(5): 349–57

    Article  PubMed  CAS  Google Scholar 

  5. Bradbrook ID, Magnani HN, Moelker HC, et al. ORG 10172: a low molecular weight heparinoid anticoagulant with a long half-life in man. Br J Clin Pharmacol 1987 Jun; 23(6): 667–75

    Article  PubMed  CAS  Google Scholar 

  6. ten Cate H, Henny CP, ten Cate JW, et al. Anticoagulant effects of a low molecular weight heparinoid (Org 10172) in human volunteers and haemodialysis patients. Thromb Res 1985 Jul 15; 39(2): 211–22

    Article  PubMed  Google Scholar 

  7. Stiekema JC, Wijnand HP, Van Dinther TG, et al. Safety and pharmacokinetics of the low molecular weight heparinoid Org 10172 administered to healthy elderly volunteers. Br J Clin Pharmacol 1989 Jan; 27(1): 39–48

    Article  PubMed  CAS  Google Scholar 

  8. Danhof M, de Boer A, Magnani HN, et al. Pharmacokinetic considerations on Orgaran (Org 10172) therapy. Haemostasis 1992; 22(2): 73–84

    PubMed  CAS  Google Scholar 

  9. Kroon C, De Boer A, Kroon JM, et al. Comparison of the bioavailability of heparin and low molecular weight heparin(oids) after subcutaneous administration in healthy volunteers. Br J Clin Pharmacol 1993; 35(5): 535

    Google Scholar 

  10. de Boer A, Danhof M, Cohen AF, et al. Interaction study between Org 10172, a low molecular weight heparinoid, and acetylsalicylic acid in healthy male volunteers. Thromb Haemost 1991 Aug 1; 66(2): 202–7

    PubMed  Google Scholar 

  11. de Boer A, Stiekema JC, Danhof M, et al. Interaction of ORG 10172, a low molecular weight heparinoid, and digoxin in healthy volunteers. Eur J Clin Pharmacol 1991; 41(3): 245–50

    Article  PubMed  Google Scholar 

  12. de Boer A, Stiekema JC, Danhof M, et al. Influence of chlorthalidone on the pharmacokinetics and pharmacodynamics of Org 10172 (Lomoparan), a low molecular weight heparinoid, in healthy volunteers. J Clin Pharmacol 1991 Jul; 31(7): 611–7

    PubMed  Google Scholar 

  13. de Boer A, Stiekema JC, Danhof M, et al. Studies of interaction of a low-molecular-weight heparinoid (Org 10172) with cloxacillin and ticarcillin in healthy male volunteers. Antimicrob Agents Chemother 1991 Oct; 35(10): 2110–5

    Article  PubMed  Google Scholar 

  14. De Boer A, Stiekema JC, Danhof M, et al. The influence of Org 10172, a low molecular weight heparinoid, on antipyrine metabolism and the effect of enzyme induction on the response to Org 10172. Br J Clin Pharmacol 1991 Jul; 32(1): 23–9

    Article  PubMed  Google Scholar 

  15. Elalamy I, Lecrubier C, Horellou MH, et al. Heparin-induced thrombocytopenia: laboratory diagnosis and management. Ann Med 2000 Dec; 32 Suppl. 1: 60–7

    Google Scholar 

  16. Warkentin TE, Chong BH, Greinacher A. Heparin-induced thrombocytopenia: towards consensus. Thromb Haemost 1998; 79: 1–7

    PubMed  CAS  Google Scholar 

  17. Warkentin TE. Heparin-induced thrombocytopenia. Pathogenesis, frequency, avoidance and management. Drug Saf 1997 Nov; 17(5): 325–41

    CAS  Google Scholar 

  18. Tardy-Poncet B, Tardy B. Heparin-induced thrombocytopenia: minimising the risks in the elderly patient. Drugs Aging 2000 May; 16(5): 351–64

    Article  PubMed  CAS  Google Scholar 

  19. Chong BH, Gallus AS, Cade JF, et al. Prospective randomised open-label comparison of danaparoid with dextran 70 in the treatment of heparin-induced thrombocytopenia with thrombosis. Thromb Haemost 2001 Nov; 86: 1170–5

    PubMed  CAS  Google Scholar 

  20. Farner B, Eichler P, Kroll H, et al. A comparison of danaparoid and lepirudin in heparin-induced thrombocytopenia. Thromb Haemost 2001 Jun; 85(6): 950–7

    PubMed  CAS  Google Scholar 

  21. Magnani HN. Orgaran (danaparoid sodium) use in the syndrome of heparin-induced thrombocytopenia. Platelets 1997; 8: 74–81

    Google Scholar 

  22. 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 Jun; 115(6): 1616–20

    Article  PubMed  CAS  Google Scholar 

  23. Tardy-Poncet B. French experience in the use of Orgaran as an alternative antithrombotic treatment for patients with heparin induced thrombocytopenia. Thromb Haemost 1997 Jun; Suppl.: 447

  24. Chong BH. Danaproid for the treatment of heparin-induced thrombocytopenia. Warkentin TE, Greinacher A. Heparin-induced Thrombocytopenia. New York: Marcel Dekker, 2000: 291–310

    Google Scholar 

  25. Lindhoff-Last E, Betz C, Bauersachs R. Use of a low-molecular weight heparinoid (danaparoid sodium) for continuous renal replacement therapy in intensive care patients. Clin Appl Thrombosis Hemostasis 2001; 7(4): 300–4

    Article  CAS  Google Scholar 

  26. Gill J, Kovacs MJ. Successful use of danaparoid in treatment of heparin-induced thrombocytopenia during twin pregnancy. Obstetrics & Gynecology 1997; 90 (4 II Suppl.): 648–50

    Article  CAS  Google Scholar 

  27. Henny CP, ten Cate H, ten Cate JW, et al. Thrombosis prophylaxis in an AT III deficient pregnant woman: application of a low molecular weight heparinoid [letter]. Thromb Haemost 1986 Apr 30; 55(2): 301

    PubMed  CAS  Google Scholar 

  28. Boshkov LK, Hamilton P, Lee A, et al. Successful therapy of heparin-induced thrombocytopenia with thrombosis in pregnancy with danaparoid sodium (Orgaran). Blood 1999 Nov 15; 94 (Suppl. 1. Pt 2): 102

    Google Scholar 

  29. Macchi L, Sarfati R, Guicheteau M, et al. Thromboembolic prophylaxis with danaparoid (Orgaran) in a high- thrombosis-risk pregnant woman with a history of heparin-induced thrombocytopenia (HIT) and Widal’s disease. Clin Appl Thromb Hemost 2000 Oct; 6(4): 187–9

    Article  PubMed  CAS  Google Scholar 

  30. Taylor AA. Successful use of heparinoids in a pregnancy complicated by allergy to heparin. Br J Obstet Gynaecol 2001 Sep; 108: 1011–2

    Article  CAS  Google Scholar 

  31. Horellou MH, Conard J, Achkar A, et al. Successful therapy with ORG 10172 in a protein S deficient pregnant woman with suspected heparin associated thrombocytopenia, DIC and thrombosis. Haemostasis 1996; 26 Suppl. 3: abstr. 73

    Google Scholar 

  32. van Besien K, Hoffman R, Golichowski A. Pregnancy associated with lupus anticoagulant and heparin induced thrombocytopenia: management with a low molecular weight heparinoid. Thromb Res 1991 Apr; 62(1–2): 23–9

    Article  PubMed  Google Scholar 

  33. Harrison SJ, Rafferty I, McColl MD. Management of heparin allergy during pregnancy with danaparoid. Blood Coagul Fibrinolysis 2001 Mar; 12(2): 157–9

    Article  PubMed  CAS  Google Scholar 

  34. ORGARAN. ABPI Compendium of Data Sheets and Summaries of Product Characteristics 1999–2000, 1090–1

  35. Zohrer B, Zenz W, Rettenbacher A, et al. Danaparoid sodium (Orgaran) in four children with heparin-induced thrombocytopenia type II. Acta Paediatr 2001 Jul; 90(7): 765–71

    Article  PubMed  CAS  Google Scholar 

  36. Saxon BR, Black MD, Edgell D, et al. Pediatric heparin-induced thrombocytopenia: management with danaparoid (Orgaran). Ann Thorac Surg 1999 Sep; 68(3): 1076–8

    Article  PubMed  CAS  Google Scholar 

  37. Neuhaus TJ, Goetschel P, Schmugge M, et al. Heparin-induced thrombocytopenia type II on hemodialysis: switch to danaparoid. Pediatr Nephrol 2000 Aug; 14(8–9): 713–6

    Article  PubMed  CAS  Google Scholar 

  38. Ranze O, Ranze P, Magnani HN, et al. Heparin-induced thrombocytopenia in paediatric patients — a review of the literature and a new case treated with danaparoid sodium. Eur J Pediatr 1999 Dec; 158 Suppl. 3: S130–3

    Article  PubMed  Google Scholar 

  39. Koster A, Meyer O, Hausmann H, et al. In vitro cross-reactivity of danaparoid sodium in patients with heparin- induced thrombocytopenia type II undergoing cardiovascular surgery. J Clin Anesth 2000 Jun; 12(4): 324–7

    Article  PubMed  CAS  Google Scholar 

  40. Magnani HN, Beijering RJR, Ten Cate JW, et al. Orgaran anti-coagulation for cardiopulmonary bypass in patients with heparin-induced thrombocytopenia. Pifarre R. New anticoagulants for the cardiovascular patient. Philadelphia: Hanley & Belfus, 1997: 487–500

    Google Scholar 

  41. 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 Nov; 15(6): 531–9

    PubMed  CAS  Google Scholar 

  42. Olin DA, Urdaneta F, Lobato EB. Use of danaparoid during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia. J Cardiothorac Vasc Anesth 2000 Dec; 14(6): 707–9

    Article  PubMed  CAS  Google Scholar 

  43. Insler SR, Kraenzler EJ, Bartholomew JR, et al. Thrombosis during the use of the heparinoid Organon 10172 in a patient with heparin-induced thrombocytopenia. Anesthesiology 1997 Feb; 86(2): 495–8

    Article  PubMed  CAS  Google Scholar 

  44. Alvarez MJ, Mezzatesta PJ. Aprotinin and Organon 10172: a successful combination for coronary artery bypass surgery complicated by heparin-induced thrombocytopenia. Aust N Z J Surg 2000 Nov; 70(11): 819–21

    Article  PubMed  CAS  Google Scholar 

  45. 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 N Z J Med 1991 Feb; 21(1): 52–4

    Article  PubMed  CAS  Google Scholar 

  46. Grocott HP, Root J, Berkowitz SD, et al. Coagulation complicating cardiopulmonary bypass in a patient with heparin-induced thrombocytopenia receiving the heparinoid, danaparoid sodium. J Cardiothorac Vasc Anesth 1997 Dec; 11(7): 875–7

    Article  PubMed  CAS  Google Scholar 

  47. Wilhelm MJ, Schmid C, Kececioglu D, et al. Cardiopulmonary bypass in patients with heparin-induced thrombocytopenia using Org 10172. Ann Thorac Surg 1996 Mar; 61(3): 920–4

    Article  PubMed  CAS  Google Scholar 

  48. Sharma S, Newman M, Gibbs N, et al. Cardiopulmonary bypass using lomoparan: monitoring of anticoagulation using anti-Xa levels and thromboelastography. Aust N Z J Surg 1997 Jun; 67(6): 392–4

    Article  PubMed  CAS  Google Scholar 

  49. Kanagasabay RR, Unsworth-White MJ, Robinson G, et al. Cardiopulmonary bypass with danaparoid sodium and ancrod in heparin- induced thrombocytopenia. Ann Thorac Surg 1998 Aug; 66(2): 567–9

    Article  PubMed  CAS  Google Scholar 

  50. Gitlin SD, Deeb GM, Yann C, et al. Intraoperative monitoring of danaparoid sodium anticoagulation during cardiovascular operations. J Vasc Surg 1998 Mar; 27(3): 568–75

    Article  PubMed  CAS  Google Scholar 

  51. Gillis S, Merin G, Zahger D, et al. Danaparoid for cardiopulmonary bypass in patients with previous heparin- induced thrombocytopenia. Br J Haematol 1997 Sep; 98(3): 657–9

    Article  PubMed  CAS  Google Scholar 

  52. Doherty DC, Ortel TL, de Bruijn N, et al. “Heparin-free” cardiopulmonary bypass: first reported use of heparinoid (Org 10172) to provide anticoagulation for cardiopulmonary bypass. Anesthesiology 1990 Sep; 73(3): 562–5

    Article  PubMed  CAS  Google Scholar 

  53. Christiansen S, Geiger A, Splittgerber FH, et al. Coronary artery bypass grafting in a patient with type II heparin associated thrombopenia. Cardiovasc Surg 1998 Feb; 6(1): 90–3

    Article  PubMed  CAS  Google Scholar 

  54. Aouifi A, Blanc P, Piriou V, et al. Cardiac surgery with cardiopulmonary bypass in patients with type II heparin-induced thrombocytopenia. Ann Thorac Surg 2001 Feb; 71(2): 678–83

    Article  PubMed  CAS  Google Scholar 

  55. Ariano RE, Bhattacharya SK, Moon M, et al. Failure of danaparoid anticoagulation for cardiopulmonary bypass. J Thorac Cardiovasc Surg 2000 Jan; 119(1): 167–8

    Article  PubMed  CAS  Google Scholar 

  56. Nicolaides AN, Breddin HK, Fareed J, et al. Prevention of Venous Thromboembolism. International Consensus Statement. Guidelines compiled in accordance with the scientific evidence. Int Angiol 2001; 20(1): 1–37

    CAS  Google Scholar 

  57. Bick RL. Proficient and cost-effective approaches for the prevention and treatment of venous thrombosis and thromboembolism. Drugs 2000; 60(3): 575–95

    Article  PubMed  CAS  Google Scholar 

  58. Mozurkewich EL. Preventing postsurgical deep venous thrombosis. Female Patient Ob Gyn Ed 1997 Mar; 22: 66–72

    Google Scholar 

  59. Hirsh J, Hoak J. Management of deep vein thrombosis and pulmonary embolism: a statement for healthcare professionals. Circulation 1996 Jun 15; 93: 2212–45

    Article  PubMed  CAS  Google Scholar 

  60. Gent M, Hirsh J, Ginsberg JS, et al. Low-molecular-weight heparinoid Orgaran is more effective than aspirin in the prevention of venous thromboembolism after surgery for hip fracture. Circulation 1996 Jan 1; 93(1): 80–4

    Article  PubMed  CAS  Google Scholar 

  61. Gerhart TN, Yett HS, Robertson LK, et al. Low-molecular-weight heparinoid compared with warfarin for prophylaxis of deep-vein thrombosis in patients who are operated on for fracture of the hip. A prospective, randomized trial. J Bone Joint Surg Am 1991 Apr; 73(4): 494–502

    CAS  Google Scholar 

  62. Bergqvist D, Kettunen K, Fredin H, et al. Thromboprophylaxis in patients with hip fractures: a prospective, randomized, comparative study between Org 10172 and dextran 70. Surgery 1991 May; 109(5): 617–22

    PubMed  CAS  Google Scholar 

  63. The TIFDED Study Group. Thromboprophylaxis in hip fracture surgery: a pilot study comparing danaparoid, enoxaparin and dalteparin. Haemostasis 1999 Nov–1999 31; 29(6): 310–7

    Google Scholar 

  64. Hoek JA, Nurmohamed MT, Hamelynck KJ, et al. Prevention of deep vein thrombosis following total hip replacement by low molecular weight heparinoid. Thromb Haemost 1992; 67(1): 28–32

    PubMed  CAS  Google Scholar 

  65. Comp PC, Voegeli T, McCutchen JW, et al. A comparison of danaparoid and warfarin for prophylaxis against deep vein thrombosis after total hip replacement: The Danaparoid Hip Arthroplasty Investigators Group. Orthopedics 1998 Oct; 21(10): 1123–8

    PubMed  CAS  Google Scholar 

  66. Leyvraz P, Bachmann F, Bohnet J, et al. Thromboembolic prophylaxis in total hip replacement: a comparison between the low molecular weight heparinoid Lomoparan and heparin-dihydroergotamine. Br J Surg 1992 Sep; 79(9): 911–4

    Article  PubMed  CAS  Google Scholar 

  67. Cade JF, Wood M, Magnani HN, et al. Early clinical experience of anew heparinoid, Org 10172, in prevention of deep venous thrombosis. Thromb Res 1987 Mar 1; 45(5): 497–503

    Article  PubMed  CAS  Google Scholar 

  68. Gallus A, Cade J, Ockelford P, et al. Orgaran (Org 10172) or heparin for preventing venous thrombosis after elective surgery for malignant disease? A double-blind, randomised, multicentre comparison. ANZ-Organon Investigators’ Group. Thromb Haemost 1993 Oct 18; 70(4): 562–7

    CAS  Google Scholar 

  69. Turpie AG, Levine MN, Hirsh J, et al. Double-blind randomised trial of Org 10172 low-molecular-weight heparinoid in prevention of deep-vein thrombosis in thrombotic stroke. Lancet 1987 Mar 7; 1(8532): 523–6

    Article  PubMed  CAS  Google Scholar 

  70. Dumas R, Woitinas F, Kutnowski M, et al. A multicentre, double-blind, randomized study to compare the safety and efficacy of once-daily ORG 10172 and twice-daily low-dose heparin in preventing deep-vein thrombosis in patients with acute ischaemic stroke. Age Ageing 1994 Nov; 23(6): 512–6

    Article  PubMed  CAS  Google Scholar 

  71. Turpie AG, Gent M, Côte R, et al. A low-molecular-weight heparinoid compared with unfractionated heparin in the prevention of deep vein thrombosis in patients with acute ischemic stroke. A randomized, double-blind study. Ann Intern Med 1992 Sep 1; 117(5): 353–7

    CAS  Google Scholar 

  72. Geerts WH, Heit JA, Clagett GP, et al. Prevention of venous thromboembolism. Chest 2001; 119 Suppl. 1: 132S-75S

    Article  Google Scholar 

  73. Lensing AWA. Anticoagulation in acute ischaemic stroke: deep vein thrombosis prevention and long-term stroke outcomes. Blood Coagul Fibrinolysis 1999 Aug; 10(Pt 2): 123–7

    Google Scholar 

  74. del Zuppo GJ. Thrombolytic therapy in the treatment of stroke. Drugs 1997; 54 Suppl. 3: 90–9

    Article  Google Scholar 

  75. Sherman DG. Heparin and heparinoids in stroke. Neurology 1998 Sep; 51 (3 Suppl 3): S56–8

    Article  PubMed  CAS  Google Scholar 

  76. The Publications Committee For The Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Investigators. Low molecular weight heparinoid, ORG 10172 (danaparoid), and outcome after acute ischemic stroke: a randomized controlled trial. The Publications Committee for the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Investigators. JAMA 1998 Apr 22-1998; 279(16): 1265–72

    Google Scholar 

  77. de Valk HW, Banga JD, Wester JW, et al. Comparing subcutaneous danaparoid with intravenous unfractionated heparin for the treatment of venous thromboembolism: a randomized controlled trial. Ann Intern Med 1995 Jul 1; 123(1): 1–9

    PubMed  Google Scholar 

  78. Levi M, ten Cate H. Disseminated Intravascular Coagulation. N Engl J Med 1999; 341(8): 586–92

    Article  PubMed  CAS  Google Scholar 

  79. Kobayashi T, Terao T, Maki M, et al. Diagnosis and management of acute obstetrical DIC. Seminars in Thrombosis and Haemostasis 2001; 27(2): 161–7

    Article  CAS  Google Scholar 

  80. de Jonge E, Levi M, Stoutenbeek CP, et al. Current drug treatment strategies for disseminated intravascular coagulation. Drugs 1998 Jun; 55: 767–77

    Article  PubMed  Google Scholar 

  81. Tomera JF. Disseminated intravascular coagulation: diagnosis, treatment and related pathophysiology. Drugs Today 1998 Dec; 34: 995–1004

    Article  PubMed  CAS  Google Scholar 

  82. Yasunaga K, Kobayashi N, Aoki N, et al. Study on the clinical efficacy of KB-101 against DIC: Pilot Study. Clinical Report 1995; 29(7): 284–303-

    Google Scholar 

  83. Yasunaga K, Mori K, Kobayshi N, et al. Evaluation of clinical effect of danaparoid sodium (KB-101) on DIC: dose setting study. Clinical Report 1995; 29(9): 2373–94

    Google Scholar 

  84. Hirayama A, Uehara S, Tsuji Y, et al. The clinical efficacy of danaparoid sodium (KB-101) against Disseminated Intravascular Coagulation (DIC). Clinical Report 1995; 29(10): 2611–30

    Google Scholar 

  85. Yasunaga K, Ogawa N, Mori K, et al. Evaluation of Clinical Effect of Danaparoid Sodium (KB-101) on Disseminated Intravascular Coagulation (DIC): double Blind Comparative Study. Jpn Pharmacol Ther 1995; 23(10): 179–98

    Google Scholar 

  86. Nieuwenhuis HK, Sixma JJ. Treatment of disseminated intravascular coagulation in acute promyelocytic leukemia with low molecular weight heparinoid Org 10172. Cancer 1986 Aug 1; 58(3): 761–4

    Article  PubMed  CAS  Google Scholar 

  87. van der Pijl JW, van der Woude FJ, Geelhoed-Duijvestijn PH, et al. Danaparoid sodium lowers proteinuria in diabetic nephropathy. J Am Soc Nephrol 1997 Mar; 8(3): 456–62

    PubMed  Google Scholar 

  88. van der Pijl JW, van der Woude FJ, Swart W, et al. Effect of danaparoid sodium on hard exudates in diabetic retinopathy. Lancet 1997 Dec 13; 350(9093): 1743–5

    Article  PubMed  Google Scholar 

  89. van der Pijl JW, Lemkes HH, Frölich M, et al. Effect of danaparoid sodium on proteinuria, von Willebrand factor, and hard exudates in patients with diabetes mellitus type 2. J Am Soc Nephrol 1999 Jun; 10(6): 1331–6

    PubMed  Google Scholar 

  90. Henny CP, ten Cate H, Surachno S, et al. The effectiveness of a low molecular weight heparinoid in chronic intermittent haemodialysis. Thromb Haemost 1985 Aug 30; 54(2): 460–2

    PubMed  CAS  Google Scholar 

  91. Frei U, Wilks MF, Boehmer S, et al. Gastrointestinal blood loss in haemodialysis patients during use of a low molecular-weight heparinoid anticoagulant. Nephrol Dial Transplant 1988; 3: 435–9

    PubMed  CAS  Google Scholar 

  92. Von Bonsdorff M, Stiekema J, Harjanne A, et al. A new low molecular weight heparinoid Org 10172 as anticoagulant in hemodialysis. Int J Artif Organs 1990 Feb; 13(2): 103–8

    Google Scholar 

  93. Ireland H, Lane DA, Flynn A, et al. The anticoagulant effect of heparinoid ORG 10172 during haemodialysis: an objective assessment. Thromb Haemost 1986; 55(2): 271–5

    PubMed  CAS  Google Scholar 

  94. Henny CP, Ten Cate H, Ten Cate JW, et al. Use of a new heparinoid as anticoagulant during acute haemodialysis of patients with bleeding complications. Lancet 1983 Apr 23; 1(8330): 890–3

    Article  PubMed  CAS  Google Scholar 

  95. ORGARAN (danaparoid sodium). European Package Insert. 2000. Organon Ltd. The Netherlands.

  96. ORGARAN (danaparoid sodium). US Package Insert. 2000. Organon Ltd. The Netherlands.

  97. Albers GW, Amarenco P, Easton JD, et al. Antithrombotic and thrombolytic therapy for ischemic stroke. Chest 2001; 119: 300S-20S

    Article  Google Scholar 

  98. Hyers TM, Agnelli G, Hull RD, et al. Antithrombotic therapy for venous thromboembolic disease. Chest 2001; 119 Suppl 1: 176S-93S

    Article  Google Scholar 

  99. Hirsh J, Warkentin TE, Shaughnessy SG, et al. Heparin and low-molecular weight heparin. Mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy, and safety. Chest 2001; 119 Suppl. 1: 64S-94S

    Google Scholar 

  100. Midori Kondo L, Wittkowsky AK, Wiggins BS, et al. Argatroban for prevention and treatment of thromboembolism in heparin-induced thrombocytopenia. Ann Pharmacother 2001; 35: 440–51

    Article  Google Scholar 

  101. Ortel TL, Chong BH. New treatment options for heparin-induced thrombocytopenia. Semin Hematol 1998; 35(4): 26–34

    PubMed  CAS  Google Scholar 

  102. Warkentin TE. Limitations of conventional treatment options for heparin-induced thrombocytopenia. Semin Hematol 1998; 35(4): 17–25

    PubMed  CAS  Google Scholar 

  103. Wade WE. Cost effectiveness of danaparoid compared with enoxaparin as deep vein thrombosis prophylaxis after hip replacement surgery. Am J Orthop 1999 Apr; 28(4): 229–31

    PubMed  CAS  Google Scholar 

  104. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue Plasminogen Activator for acute ischaemic stroke. N Engl J Med 1995; 333(24): 1581–7

    Article  Google Scholar 

  105. Kay R, Wong KS, Yu YL, et al. Low molecular weight heparin for the treatment of acute ischemic stroke. N Engl J Med 1995; 333(24): 1588–93

    Article  PubMed  CAS  Google Scholar 

  106. Baglin T. Disseminated Intravascular Coagulation: diagnosis and treatment. Br Med J 1996; 312: 683–6

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland, 10, New Zealand

    Tim Ibbotson & Caroline M. Perry

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  1. Tim Ibbotson
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  2. Caroline M. Perry
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Correspondence to Tim Ibbotson.

Additional information

Various sections of the manuscript reviewed by: JE Ahaneku, Department of Clinical Pathology, Nnamdi Azikiwe University Nnewi, Anambra State, Nigeria; H Asakura, Department of Internal Medicine III, Kanazawa University School of Medicine, Kanazawa, Japan; A Gallus, Department of Haematology, Flinders Medical Centre, Adelaide, Australia; R Hamada, Department of Neurology, National Hospital Kyushu Cardiovascular Centre, Kagoshima City, Japan; DG Sherman, Department of Medicine, University of Texas Health Science Center, San Antonio, Texas, USA.

Data Selection

Sources: Medical literature published in any language since 1980 on danaparoid sodium, identified using Medline and EMBASE, supplemented by AdisBase (a proprietary database of Adis International). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: Medline search terms were ‘danaparoid’ or ‘KB-101’. EMBASE search terms were ‘danaparoid sodium’ or ‘danaparoid’. AdisBase search terms were ‘danaparoid sodium’ or ‘danaparoid’ or ‘KB-101’. Searches were last updated 11th September 2002.

Selection: Studies in patients with deep vein thrombosis, heparin-induced thrombocytopenia or disseminated intravascular coagulation who received danaparoid. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: danaparoid, deep vein thrombosis, heparin-induced thrombocytopenia, disseminated intravascular coagulation, pharmacodynamics, pharmacokinetics, therapeutic use.

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Ibbotson, T., Perry, C.M. Danaparoid. Drugs 62, 2283–2314 (2002). https://doi.org/10.2165/00003495-200262150-00016

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