Low Molecular Weight Heparin’s Mechanism of Action

• REFERENCES

• 1 Fareed J, Walenga JM, Kumar A, Rock A. A modified stasis thrombosis model to study the antithrombotic actions of heparin and its fractions. Semin Thromb Hemost 1985; 11: 155-75.
• 2 Fareed J, Walenga JM, Hoppensteadt D, Huan X, Racanelli A. Comparative study on the in vitro and in vivo activities of seven low molecular weight heparins. Haemostasis 1989; 18 (Suppl. 03) 3-15.
• 3 Abildgaard U, Sandset P, Lindahl A. Tissue factor pathway inhibitor. In: Poller L. (ed). Recent Advances in Blood Coagulation. Churchill Livingstone. 1993: 105-24.
• 4 Broze GJ. Tissue factor pathway inhibitor and the current concept of blood coagulation. Blood Coag Fibrinol 1995; 06 (01) S7-13.
• 5 Van Dedem G, Nielsen JI. Determinations of the molecular mass of low molecular mass (LMM) heparin. Pharmeuropa 1991; 03: 202-18.
• 6 Fareed J, Walenga JM, Lassen M, Borris L, Hoppensteadt DA, Murphy R, Ahsan A, Weber S, Jorgensen LN, Hauch O. Pharmacologic profile of a low molecular weight heparin (Enoxaparin): Experimental and clinical validation of the prophylactic antithrombotic effects. Acta Chir Scand 1990; 56 (Suppl. 556) 75-90.
• 7 Raake W, Elling H. Rat jugular vein hemostasis a new model for testing antithrombotic agents. Thromb Res 1989; 53: 73-7.
• 8 Cade JF, Buchanan MR, Boneu B, Ockelford P. A comparison of the antithrombotic and haemorrhagic effects of low molecular weight heparin fractions: the influence of the preparation. Thromb Res 1984; 35: 613.
• 9 Fareed J, Kumar A, Rock A, Walenga JM, Davis P. A primate model (macaca mulatta) to study the pharmacokinetics of heparin and its fractions. Semin Thromb Hemost 1985; 11: 138.
• 10 Samama M. Contemporary laboratory monitoring of low molecular weight heparins. Thromb Hemost 1995; 15 (01) 119-23.
• 11 Fareed J. Current trends in antithrombotic drug and device development. Semin Thromb Hemost 1996; 22 (01) 3-8.
• 12 Clagett GP, Anderson FA, Heit J, Levine MN, Wheeler HB. Prevention of venous thromboembolism. Chest 1995; 108 (04) 312S-34S.
• 13 Premmereur J. The use of low-molecularweight heparins in cardiology. In: New Anticoagulants for the Cardiovascular Patient. Pifarr JR. (ed). Philadelphia: Hanley & Belfus, Inc; 1997: 597-608.
• 14 Kalodiki E, Nicolaides AN. Low-molecularweight heparin in the treatment of deep vein thrombosis. In: New Anticoagulants for the Cardiovascular Patient. Pifarr JR. (ed). Philadelphia: Hanley & Belfus, Inc; 1997: 609-19.
• 15 Fareed J, Jeske W, Hoppensteadt D, Clarizio R, Walenga JM. Are the available low-molecular-weight heparin preparations the same?. Semin Thromb Hemost 1996; 22 (Suppl. 01) 77-91.
• 16 Hirsh J, Raschke R, Warkentin TE, Dalen JE, Deykin D, Poller L. Heparin: mechanism of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest 1995; 108 (04) 258S-75S.
• 17 Hirsh J, Hoak J. Management of deep vein thrombosis and pulmonary embolism. Circulation 1996; 93 (12) 2212-45.
• 18 Leclerc JR, Geerts WH, Desjardins L, Laflamme LH, l’Esperance B, Demers C, Kassis J, Cruickshank M, Whitman L, Delorme F. Prevention of venous thromboembolism after knee arthroplasty. A randomized, double-blind trial comparing enoxaparin with warfarin. Ann Intern Med 1996; 124 (07) 619-26.
• 19 Bergqvist D, Benoni G, Bjorgell O, Fredin H, Hedlundh U, Nicolas S, Nilsson P, Nylander G. Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med 1996; 335 (10) 696-700.
• 20 Heit JA, Berkowitz SD, Bona R, Cabanas V, Corson JD, Elliott CG, Lyons R. (Ardeparin Arthroplasty Study Group). Efficacy and safety of low molecular weight heparin (ardeparin sodium) compared to warfarin for the prevention of venous thromboembolism after total knee replacement surgery: a double-blind, dose-ranging study. Thromb Haemost 1997; 77 (01) 32-8.
• 21 Lassen MR, Borris LC. Low molecular weight heparin for the prevention of deep vein thrombosis following orthopedic surgery. Current Opinion in Pulmonary Medicine 1996; 02 (04) 300-4.
• 22 Planes A, Vochelle N, Darmon JY, Fagola M, Bellaud M, Huet Y. Risk of deep-venous thrombosis after hospital discharge in patients having undergone total hip replacement: double-blind randomised comparison of enoxaparin versus placebo. Lancet 1996; 348 9022 224-8.
• 23 Hull RD, Pineo GF, Brant RF. Effect of low molecular weight heparin versus warfarin sodium on mortality in long-term treatment of proximal vein thrombosis. Clin Appl Thrombosis/Hemostasis 1996; 02 (Suppl. 01) S4-11.
• 24 Dahl OE, Andreassen G, Aspelin T, Muller C, Mathiesen P, Nyhus S, Abdelnoor M, Solhaug JH, Arnesen H. Prolonged thromboprophylaxis following hip replacement surgery Results of a double-blind, prospective, randomised, placebo-controlled study with dalteparin (Fragmin®). Thromb Haemost 1997; 77 (01) 26-31.
• 25 Gördlund B. for The Heparin Prophylaxis Study Group. Randomised, controlled trial of low-dose heparin for prevention of fatal pulmonary embolism in patients with infectious diseases. Lancet 1996; 347 9012 1357-61.
• 26 The Columbus Investigators. Low molecular weight heparin is an effective and safe treatment for deep-vein thrombosis and pulmonary embolism. Blood 1996; 88 (10) (Suppl. 01) 626a.
• 27 Fragmin during Instability in Coronary Artery Disease (FRISC) Study Group. Low-molecular-weight heparin during instability in coronary artery disease. Lancet 1996; 347: 561-8.
• 28 Cohen M, Demers C, Gurfinkel E, Fromell G, Langer A, Turpie AGG. ESSENCE Group. Primary end point analysis from the ESSENCE trial: enoxaparin vs unfractionated heparin in unstable angina and non-Q wave infarction. Circulation 1996; 94 (08) 1-554.
• 29 Antman EM, McCabe CH, Marble SJ, Cannon CP, Feldman R, Papuchis G, Moore PB. Dose ranging trial of enoxaparin for unstable angina: results of TIMI11 A. Circulation 1996; 94 (08) 1-554.
• 30 Zidar J. New insights in the prevention of thrombosis in coronary stents the ENTICES trial and the role of enoxaparin. Ann Hematol 1997; 04 (Suppl II): A152.
• 31 Schiele FJ, Ruillemenot VA, Meneveau NF, Gupta SM, Xu CJ, Fontecave SJ, Cariou RG, Bassand JPL. Initial experience of a sulphated pentasaccharide, a pure factor Xa inhibitor, in coronary angioplasty. Circulation 1996; 94 (08) 1-742.
• 32 Hull RD, Raskob GE, Pineo GF, Green D, Trowbridge AA, Elliott CG, Lerner RG, Hall J, Sparling T, Brettell HR. Subcutaneous low-molecular-weight heparin compared with continuous intravenous heparin in the treatment of proximal vein thrombosis. N Engl J Med 1992; 326 (15) 975-82.
• 33 Prandoni P, Lensing AWA, Bhller HR, Carta M, Cogo A, Vigo M, Casara D, Ruol A, ten Cate JW. Comparison of subcutaneous low-molecular-weight heparin with intravenous standard heparin in proximal deep-vein thrombosis. Lancet 1992; 339: 441-5.
• 34 Lopaciuk S, Meissner AJ, Filipecki S, Zawilska K, Sowier J, Cielsielski L, Bielawi M, Glowinski S, Czestochowska E. Subcutaneous low molecular weight heparin versus subcutaneous unfractionated heparin in the treatment of deep vein thrombosis: a Polish multicenter trial. Thromb Haemost 1992; 68: 14-8.
• 35 Lindmarker P, Holmstrom M, Granqvist S, Johnsson H, Lockner D. Comparison of once-daily subcutaneous Fragmin with continuous intravenous unfractionated heparin in the treatment of deep venous thrombosis. Thromb Haemost 1994; 72: 186-90.
• 36 Simonneau G, Charbonnier B, Docousus H, Planchon B, Ninet J, Sie P, Selsiguen M, Combe S. Subcutaneous low molecular weight heparin compared with continuous intravenous unfractioned heparin in the treatment of proximal deep vein thrombosis. Arch Intern Med 1993; 153 (13) 1541-6.
• 37 Raskob GE. Low molecular weight heparin for the prevention and treatment of venous thromboembolism. Current Opinion in Pulmonary Medicine 1996; 02 (04) 305-10.
• 38 Koopman MMW, Prandoni P, Piovella F, Ockelford PA, Brandjes DPM, van der Meer J, Gallus AS, Simonneau G, Chesterman CH, Prins MH, Bossuyt PMM, de Haes H, van den Belt AGM, Sagnard L, d’Azemar P, Buller HR. for The TASMAN Study Group. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. N Engl J Med 1996; 334 (11) 682-7.
• 39 Levine M, Gent M, Hirsh J, Leclerc J, Anderson D, Weitz J, Ginsberg J, Turpie AG, Demers C, Kovacs M. A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis. N Engl J Med 1996; 334 (11) 677-81.
• 40 Godwin J. Use of low molecular weight heparins in malignancy-related thromboembolic disorders: a clinical review. Clin Appl Thrombosis/Hemostasis 1996; 02 (Suppl. 01) S28-34.
• 41 Fricker JP, Vergnes Y, Schach R, Heitz A, Eber M, Grunebau M, Wiesel ML, Kher A, Barbier P, Cazenave JP. Low dose heparin versus low molecular weight heparin (Kabi 2165, Fragmin) in the prophylaxis of thromboembolic complications of abdominal oncological surgery. Eur J Clin Invest 1988; 08: 561-7.
• 42 Enke A, Breddin K. Comparison of a low molecular weight heparin and unfractionated heparin for the prevention of deep vein thrombosis in patients undergoing abdominal surgery. Br J Surg 1988; 75: 1058.
• 43 Godwin JE, Comp P, Davidson B, Rossi M. The Normiflo™ Cancer Clinical Trial Group. Comparison of the efficacy and safety of subcutaneous RD heparin vs subcutaneous unfractionated heparin for the prevention of deep-vein thrombosis in patients undergoing abdominal or pelvic surgery for cancer. Thromb Haemost 1996; 69 (Suppl): 376.
• 44 Prandoni P, Lensing AWA, Bhller HR, Cogo A, Prins MH, Cattelan AM, Cuppini S, Noventa F, ten Cate JW. Deep-vein-thrombosis and the incidence of subsequent symptomatic cancer. N Engl J Med 1992; 327: 1128-33.
• 45 Monreal M, Lafoz E, Olive A, del Rio L, Vedia C. Comparison of subcutaneous unfractionated heparin with a low molecular weight heparin (Fragmin) in patients with venous thromboembolism and contraindications to coumarin. Thromb Haemost 1994; 71: 7-11.
• 46 Salazar E, Izaguirre R, Verdejo J, Mutchinick O. Failure of adjusted doses of subcutaneous heparin to prevent thromboembolic phenomena in pregnant patients with mechanical cardiac valve prostheses. J Am Coll Cardiol 1996; 127 (07) 1698-703.
• 47 Hunt BJ, Doughty HA, Majumdar G, Copplestone A, Kerslake S, Buchanan N, Hughes G, Khamashta M. Thromboprophylaxis with low molecular weight heparin (fragmin) in high risk pregnancies. Thromb Haemost 1997; 77 (01) 39-43.
• 48 Boda Z, Laszlo P, Rejtt L, Tornai I, Pfliegler G, Blasko G, Rak K. Low molecular weight heparin as thromboprophylaxis in familial thrombophilia during the whole period of pregnancy. Thromb Haemost 1996; 76 (01) 124-8.
• 49 Massicotte P, Adams M, Marzinotto V, Brooker LA, Andrew M. Low-molecularweight heparin in pediatric patients with thrombotic disease: a dose finding study. J Pediatr 1996; 128: 313-8.
• 50 Forrat R, Ferrera R, Boissonnat P, Adeleine P, Dureau G, Ninet J, de Lorgeril M. High prevalence of thromboembolic complications in heart transplant recipients. Transplantation 1996; 61 (05) 757-62.
• 51 Walenga JM, Koza MJ, Lewis BE, Pifarre R. Relative heparin-induced thrombocytopenic potential of low molecular weight heparins and new antithrombotic agents. Clin Appl Thrombosis/Hemostasis 1996; 02 (Suppl. 01) S21-7.
• 52 Greinacher A, Feigl M, Mueller-Eckhardt C. Crossreactivity studies between sera of patients with heparin associated thrombocytopenia and a new low molecular weight heparin, reviparin. Thromb Haemost 1994; 72 (04) 644-5.
• 53 Greinacher A, Alban S, Dummei V, Franz G, Mueller-Eckhardt C. Characterization of the structural requirements for a carbohydrate based anticoagulant with a reduced risk of inducing the immunological type of heparin-associated thrombocytopenia. Thromb Haemost 1995; 74 (03) 886-92.
• 54 Warkentin TE, Levine MN, Hirsh J, Horsewood P, Roberts RS, Gent M, Kelton JG. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med 1995; 332 (20) 1330-5.
• 55 Brieger D, Dawes J. Production method affects the pharmacokinetic and ex vivo biological properties of low molecular weight heparins. Thromb Haemost 1997; 77 (02) 317-22.
• 56 Collignon F, Frydman A, Caplain H, Ozoux ML, Le Roux Y, Bouthier J, Thebault JJ. Comparison of the pharmacokinetic profiles of three low molecular mass heparins dalteparin, enoxaparin and nadroparin administered subcutaneously in healthy volunteers (doses for prevention of thromboembolism). Thromb Haemost 1995; 73 (04) 630-40.
• 57 Eriksson BI, Söderberg K, Widlund L, Wandeli B, Tengborn L, Risberg B. A comparative study of three low-molecular weight heparins (LMWH) and unfractionated heparin (UH) in healthy volunteers. Thromb Haemost 1995; 73 (03) 398-401.
• 58 Fareed J, Walenga JM, Hoppensteadt D, Huan X, Nonn R. Biochemical and pharmacologic inequivalence of low molecular weight heparins. Ann NY Acad Sci 1989; 556: 333-53.
• 59 Boneu B. Low molecular weight heparin therapy: is monitoring needed?. Thromb Haemost 1994; 72 (03) 330-4.
• 60 Samama M. Contemporary laboratory monitoring of low molecular weight heparins. Thromb Haemost 1995; 15 (01) 119-23.
• 61 Hoppensteadt DA, Jeske W, Fareed J. Laboratory monitoring of new anticoagulant and antithrombotic drugs. In: New Anticoagulants for the Cardiovascular Patient. Pifarr JR. (ed). Philadelphia: Hanley & Belfus, Inc; 1997: 521-38.
• 62 Hawkins DW. Global economic perspective on the use of low molecular weight heparin. Clin Appl Thrombosis/Hemostasis 1996; 02 (Suppl. 01) S40-3.
• 63 Hull RD, Feldstein W, Stein PD, Pineo GF. Cost-effectiveness of pulmonary embolism diagnosis. Arch Intern Med 1996; 156: 68-72.
• 64 Ahsan A, Jeske W, Hoppensteadt D, Lormeau JC, Wolf H, Fareed J. Molecular profiling and weight determination of heparins and depolymerized heparins. J Pharm Sci 1995; 84 (06) 724-7.
• 65 Mulloy B, Gee C, Wheeler SF, Wait R, Gray E, Barrowcliffe TW. Molecular weight measurements of low molecular weight heparins by gel permeation chromatography. Thromb Haemost 1997; 77 (04) 668-74.
• 66 Woltz M, Eder M, Weltermann A, Entlicher J, Eichler HG, Kyrle PA. Comparison of the effects of different low molecular weight heparins on the hemostatic system activation in vivo in man. Thromb Haemost 1997; 78: 876-9.
• 67 Azizi M, Veyssier-Belot C, Alhenc-Gelas M, Chatellier G, Billaud-Mesguish E, Fiessinger JN, Aiach M. Comparison of biologic activities of two low molecular weight heparins in 10 healthy volunteers. Br J Clin Pharmacol 1995; 40: 577-84.
• 68 Klein W, Buchwald A, Hillis SE, Monrad S, Sanz G, Turpie AGG, van der Meer J, Olaisson E, Undeland S, Ludwig K. Comparison of low-molecular-weight heparin with unfractionated heparin acutely and with placebo for 6 weeks in the management of unstable coronary artery disease. Fragmin in Unstable Coronary Artery Disease Study (FRIC). Circulation 1997; 96 (01) 61-8.
• 69 Waters D, Azar R. Low-molecular-weight heparins for unstable angina. A better mousetrap? Circulation 1997; 96 (01) 3-5.
• 70 Cohen M, Demers C, Gurfinkel EP, Turpie AGG, Fromell GJ, Goodman S, Langer A, Califf RM, Fox KAA, Premmereur J, Bigonzi F. A comparison of low-molecularweight heparin with unfractionated heparin for unstable coronary artery disease. N Eng J Med 1997; 337 (07) 447-52.