Subscribe to RSS
DOI: 10.1055/s-0038-1646390
Interaction Study between Org 10172, a Low Molecular Weight Heparinoid, and Acetylsalicylic Acid in Healthy Male Volunteers
Publication History
Received 19 January 1990
Accepted 30 January 1991
Publication Date:
25 July 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199102/lookinside/thumbnails/10-1055-s-0038-1646390-1.jpg)
Summary
Potential interactions between Org 10172 (Lomoparan®; i. v. bolus injection of 3,250 anti-Xa units followed by 750 units twice daily s. c. for 8 days) and acetylsalicylic acid (ASA) (500 mg orally 14 and 2 h before i. v. Org 10172 administration) were studied in eight healthy male volunteers using an open, randomised three-way cross-over design. Except for moderate bruising at venepuncture and s.c. injection sites which were equally distributed over all three treatments (Org 10172 alone, ASA alone, Org 10172 and ASA combined), no side effects were observed. The effects of the separate drugs on several haemostatic parameters were as expected, although the prolongations in bleeding time after ASA were highly variable and tended to be somewhat more pronounced after the combination (p >0.05). Org 10172 did not influence the inhibiting effects of ASA on platelet function nor the functional recovery afterwards, as evaluated by thromboxane A2 (TXA2) generation and collagen-induced platelet aggregation. Furthermore, no important interactions were observed with regard to the coagulation tests and plasma anti-Xa activity. Although this study did not entirely exclude small interactions between Org 10172 and ASA in this relatively small group of subjects, these effects are probably without clinical significance.
-
References
- 1 Meuleman DG, Hobbelen PMJ, Van Dedem G, Moelker HCT. A novel anti-thrombotic heparinoid (Org 10172) devoid of bleeding inducing capacity: a survey of its pharmacological properties in experimental animal models. Thromb Res 1982; 27: 353-63
- 2 Hobbelen PMJ, Vogel GMT, Meuleman DG. Time courses of the antithrombotic effects, bleeding enhancing effects and interactions with factors Xa and thrombin after administration of low molecular weight heparinoid Org 10172 or heparin to rats. Thromb Res 1987; 48: 549-58
- 3 Harenberg J, Zimmerman R, Schwarz F, Kubler W. Treatment of heparin-induced thrombocytopaenia with thrombosis by new heparinoid. Lancet 1983; i: 986-7
- 4 Henny ChP, Ten Cate JW, Van Bronswijk H, Ten Cate H, Surachno S, Wilmink JH. Use of a new heparinoid as anticoagulant during acute haemodialysis of patients with bleeding complications. Lancet 1983; i: 980-93
- 5 Ten Cate H, Henny CP, Buller HR, Ten Cate JW, Magnani HN. Use of a heparinoid in patients with haemorrhagic stroke and thromboembolic disease. Ann Neurol 1984; 15: 268-70
- 6 Kiers L, Grigg LE, Cade JF, Street PR, Chong BH. Use of Org 10172 in the treatment of heparin induced thrombocytopaenia and thrombosis. Aust N Z J Med 1986; 16: 179
- 7 Cade J, Gallus A, Ockelford P, Magnani H. Org 10172 or heparin for preventing venous thrombosis (VT) after surgery for malignant disease? A double-blind, multi-centre comparison. Thromb Haemostas 1989; 62: 42 (Abstr 96)
- 8 Blum A, Desruennes E, Elias A, Lagrange G, Loriferne JE. DVT prophylaxis in surgery for digestive tract cancer comparing the LMW heparinoid Org 10172 (Lomoparan) with calcium heparin. Thromb Haemostas 1989; 62: 126 (Abstr 400)
- 9 Estoppey D, Hochreiter J, Breyer HG, Jakubek H, Leyvraz PF, Haas S, Stiekema JCJ. Org 10172 (Lomoparan) versus heparin-DHE in prevention of thromboembolism in total hip replacement – A multicentre trial. Thromb Haemostas 1989; 62: 356 (Abstr 4: 107)
- 10 Mikhailidis DP, Fonseca VA, Barradas MA, Jeremy JY, Dandona P. Platelet activation following intravenous injection of a conventional heparin: absence of effect with low molecular weight heparinoid (Org 10172). Br J Clin Pharmacol 1987; 24: 415-24
- 11 Vinazzer H, Stemberger A, Haas S, Blümel G. Influence of heparin; of different heparin fractions and of low molecular weight heparin-like substance on the mechanism of fibrinolysis. Thromb Res 1982; 27: 341-52
- 12 UK-TIA Study Group United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: interim results. Br Med J 1988; 296: 316-20
- 13 Lewis Jr HD, Davis HW, Archibald DG, Steinke WE, Smitherman TC, Doherty JE, Schnaper HW, LeWinter MM, Linares E, Pouget JM, Sabharwal SC, Chesler E, Demots H. Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. N Engl J Med 1983; 309: 396-403
- 14 ISIS-2 Collaborative Group Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17187 cases of suspected myocardial infarction: ISIS-2.. Lancet 1988: 349-60
- 15 Heiden D, Rodvien R, Mielke CH. Heparin bleeding, platelet dysfunction and Aspirin. JAMA 1981; 246: 330-1
- 16 Biggs R. Human Blood Coagulation,. Haemostasis and Thrombosis. 2nd ed.. Blackwell Scientific Publications, Oxford: 1972
- 17 Teien AN, Lie M. Evaluation of an amidolytic heparin assay method: increased sensitivity by adding purified antithrombin III. Thromb Res 1977; 10: 399-410
- 18 Mielke CH, Kaneshiro MM, Maher IA. The standardised normal Ivy bleeding and its prolongation by aspirin. Blood 1969; 34: 204-15
- 19 Stiekema JCJ, Wijnand HP, Van Dinther THG, Moelker HCT, Dawes J, Vinchenzo A, Toeberich H. Safety and pharmacokinetics of the low molecular weight heparinoid Org 10172 administered to healthy eldery volunteers. Br J Clin Pharmacol 1989; 27: 38-9
- 20 De Boer A, Kroon JM, Kroon C, Van Vliet A, Breimer DD, Donoghue S, Cohen AF. Synergistic effect of a new thromboxane antagonist (GR32191) and heparin on bleeding time in healthy male volunteers. Br J Clin Pharmacol 1990; 29: 599P
- 21 Quick AJ. Salicylates and bleeding: The aspirin tolerance test. Am J Med Sci 1966; 252: 265-9
- 22 Mielke CH. Template bleeding time: technical evaluation and comparison to other methods in normal adults. In: Platelet Function Testing, DHEW Publ.. (NIH) 78-1087, Washington, DC: 1976. p 13
- 23 Eyster ME, Gordon RA, Ballard JO. The bleeding time is longer than normal in haemophilia. Blood 1981; 58: 719-23
- 24 Rosenstein R, Zacharski LR. The diagnostic value of the aspirin tolerance test. Thromb Res 1979; 16: 219-30
- 25 Kuman R, Ansell JE, Canoso RT, Deykin D. Clinical trial of a new bleeding time device. Am J Clin Pathol 1978; 70: 642-5
- 26 Czapek EE, Deykin D, Salzman E, Lian E, Hellerstein LJ, Rosoff CB. Intermediate syndrome of platelet dysfunction. Blood 1978; 52: 103-13
- 27 Bradhook ID, Magnani HN, Moelker HCT, Morrison PJ, Robinson J, Rogers HJ, Spector RG, Van Dinther T, Wijnand H. Org 10172: a low molecular weight heparinoid anticoagulant with a long half-life in man. Br J Clin Pharmacol 1987; 23: 667-75
- 28 Nieuwenhuis HK. Human blood platelet function. Clinical and biochemical aspects of platelet disorders. Ph. D. Thesis, University of Utrecht, The Netherlands, 1986; p 20.
- 29 Patrignani P, Filabozzi P, Patrono C. Selective cumulative inhibition of platelet thromboxane production by low dose aspirin in healthy subjects. J Clin Invest 1982; 69: 1366-72
- 30 Cella G, Casonato A, Visintin L, Girolami A. Heparins and release. Thromb Haemostas 1980; 44: 105
- 31 Fitzgerald DJ, Catella F, Roy L, Fitzgerald GA. Marked platelet activation in vivo after intravenous streptokinase in patients with acute myocardial infarction. Circulation 1988; 77: 142-50
- 32 Leroy J, Leclerc MH, Delahousse B, Guerois C. Treatment of heparin-associated thrombocytopenia and thrombosis with low molecular weight heparin (CY216). Semin Thromb Hemostas 1985; 11: 326-9