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Journal of Thrombosis and Thrombolysis
Published in: Journal of Thrombosis and Thrombolysis 2/2010

01-02-2010

Update on heparin: what do we need to know?

Authors: Daniel S. Weitz, Jeffrey I. Weitz

Published in: Journal of Thrombosis and Thrombolysis | Issue 2/2010

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Abstract

Over the last 15 years, there has been a shift from unfractionated heparin to low-molecular-weight heparin or fondaparinux for many indications. Nonetheless, heparin continues to be used and it remains the drug of choice for selected indications and patients. This paper reviews when and how to use heparin and when low-molecular-weight heparin or fondaparinux may be a better choice. The paper also describes some of the new parenteral anticoagulants under development and provides perspective on how the introduction of rapid-acting oral thrombin or factor Xa inhibitors is likely to reduce or eliminate the need for bridging with parenteral anticoagulants.
Literature
1.
Hirsh J, Bauer KA, Donati MB, Gould M, Samama MM, Weitz JI, American College of Chest Physicians (2008) Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest 133:141S–159SCrossRefPubMed
2.
3.
Young E, Prins M, Levine MN, Hirsh J (1992) Heparin binding to plasma proteins, an important mechanism for heparin resistance. Thromb Haemost 67:639–643PubMed
4.
Young E, Cosmi B, Weitz J, Hirsh J (1993) Comparison of the non-specific binding of unfractionated heparin and low molecular weight heparin (Enoxaparin) to plasma proteins. Thromb Haemost 70:625–630PubMed
5.
Young E, Wells P, Holloway S, Weitz J, Hirsh J (1994) Ex-vivo and in vitro evidence that low molecular weight heparins exhibit less binding to plasma proteins than unfractionated heparin. Thromb Haemost 71:300–304PubMed
6.
Othieno R, Abu Affan M, Okpo E (2007) Home versus in-patient treatment for deep vein thrombosis. Cochrane Database Syst Rev 18:CD003076
7.
Siragusa S, Cosmi B, Piovella F, Hirsh J, Ginsberg JS (1996) Low-molecular-weight heparins and unfractionated heparin in the treatment of patients with acute venous thromboembolism: results of a meta-analysis. Am J Med 100:269–277CrossRefPubMed
8.
Rocha E, Martinez-Gonzalez MA, Montes R, Panizo C (2000) Do the low molecular weight heparins improve efficacy and safety of the treatment of deep venous thrombosis? A meta-analysis. Haematologica 85:935–942PubMed
9.
Dolovich LR, Ginsberg JS, Douketis JD, Holbrook AM, Cheah G (2000) A meta-analysis comparing low-molecular-weight heparins with unfractionated heparin in the treatment of venous thromboembolism: examining some unanswered questions regarding location of treatment, product type, and dosing frequency. Arch Intern Med 160:181–188CrossRefPubMed
10.
Louzada ML, Majeed H, Wells PS (2009) Efficacy of low-molecular-weight heparin versus vitamin K antagonists for long term treatment of cancer-associated venous thromboembolism in adults: a systematic review of randomized controlled trials. Thromb Res 123:837–844CrossRefPubMed
11.
van Doormaal FF, Raskob GE, Davidson BL, Decousus H, Gallus A, Lensing AW, Piovella F, Prins MH, Buller HR (2009) Treatment of venous thromboembolism in patients with cancer: Subgroup analysis of the Matisse clinical trials. Thromb Haemost 101:762–769PubMed
12.
Chong BH, Isaacs A (2009) Heparin-induced thrombocytopenia: what clinicians need to know. Thromb Haemost 101:279–283PubMed
13.
Handschin AE, Trentz OA, Hoerstrup SP, Kock HJ, Wanner GA, Trentz O (2005) Effect of low molecular weight heparin (dalteparin) and fondaparinux (Arixtra) on human osteoblasts in vitro. Br J Surg 92:177–183CrossRefPubMed
14.
Bhandari M, Hirsh J, Weitz JI, Young E, Venner TJ, Shaughnessy SG (1998) The effects of standard and low molecular weight heparin on bone nodule formation in vitro. Thromb Haemost 80:413–417PubMed
15.
Rajgopal R, Butcher M, Weitz JI, Shaughnessy SG (2006) Heparin synergistically enhances interleukin-11 signalling through up-regulation of the MAPK pathway. J Biol Chem 281:20780–20787CrossRefPubMed
16.
Muir JM, Hirsh J, Weitz JI, Andrew M, Young E, Shaughnessy SG (1997) A histomorphometric comparison of the effects of heparin and low-molecular-weight heparin on cancellous bone in rats. Blood 89:3236–3242PubMed
17.
Hawkins D, Evans J (2005) Minimizing the risk of heparin-induced osteoporosis during pregnancy. Expert Opin Drug Saf 4:583–590CrossRefPubMed
18.
Warkentin TE, Cook RJ, Marder VJ, Sheppard JA, Moore JC, Eriksson BI, Greinacher A, Kelton JG (2005) Anti-platelet factor 4/heparin antibodies in orthopaedic surgery patients receiving antithrombotic prophylaxis with fondaparinux or enoxaparin. Blood 106:3791–3796CrossRefPubMed
19.
Rauova L, Poncz M, McKenzie SE, Reilly MP, Arepally G, Weisel JW, Nagaswami C, Cines DB, Sachais BS (2005) Ultralarge complexes of PF4 and heparin are central to the pathogenesis of heparin-induced thrombocytopenia. Blood 105:131–138CrossRefPubMed
20.
Greinacher A, Gopinadhan M, Gunther JU, Omer-Adam MA, Strobel U, Warkentin TE, Papastavrou G, Weitschies W, Helm CA (2006) Close approximation of two platelet factor 4 tetramers by charge neutralization forms the antigens recognized by HIT antibodies. Arterioscler Thromb Vasc Biol 26:2386–2393CrossRefPubMed
21.
Lobo B, Finch C, Howard A, Minhas S (2008) Fondaparinux for the treatment of patients with acute heparin-induced thrombocytopenia. Thromb Haemost 99:208–214PubMed
22.
Blackmer AB, Oertel MD, Valgus JM (2009) Fondaparinux and the management of heparin-induced thrombocytopenia: the journey continues (October). Ann Pharmacother [Epub ahead of print]
23.
Blossom DB, Kallen AJ, Patel PR, Elward A, Robinson L, Gao G, Langer R, Perkins KM, Jaeger JL, Kurkjian KM, Jones M, Schillie SF, Shehab N, Ketterer D, Venkataraman G, Kishimoto TK, Shriver Z, McMahon AW, Austen KF, Kozlowski S, Srinivasan A, Turabelidze G, Gould CV, Arduino MJ, Sasisekharan R (2008) Outbreak of adverse reactions associated with contaminated heparin. N Engl J Med 359:2674–2684CrossRefPubMed
24.
Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators, Yusuf S, Mehta SR, Chrolavicius S, Afzal R, Pogue J, Granger CB, Budaj A, Peters RJ, Bassand JP, Wallentin L, Joyner C, Fox KA (2006) Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med 354:1464–1476CrossRefPubMed
25.
Yusuf S, Mehta SR, Chrolavicius S, Afzal R, Pogue J, Granger CB, Budaj A, Peters RJ, Bassand JP, Wallentin L, Joyner C, Fox KA, OASIS-6 Trial Group (2006) Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial. JAMA 295:1519–1530CrossRefPubMed
26.
Mehta SR, Granger CB, Eikelboom JW, Bassand JP, Wallentin L, Faxon DP, Peters RJ, Budaj A, Afzal R, Chrolavicius S, Fox KA, Yusuf S (2007) Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: results from the OASIS-5 trial. J Am Coll Cardiol 50:1742–1751CrossRefPubMed
27.
Wiebe EM, Stafford AR, Fredenburgh JC, Weitz JI (2003) Mechanism of catalysis of inhibition of factor IXa by antithrombin in the presence of heparin or pentasaccharide. J Biol Chem 278:35767–35774CrossRefPubMed
28.
Yang L, Manithody C, Rezaie AR (2007) Localization of the heparin binding exosites of factor IXa. J Biol Chem 277:50756–50760CrossRef
29.
Bedsted T, Swanson R, Chuang YJ, Bock PE, Bjork I, Olson ST (2003) Heparin and calcium ions dramatically enhance antithrombin reactivity with factor IXa by generating new interaction exosites. Biochemistry 42:8143–8152CrossRefPubMed
30.
Buller HR, Davidson BL, Decousus H, Gallus A, Gent M, Piovella F, Prins MH, Raskob G, van den Berg-Segers AE, Cariou R, Leeuwenkamp O, Lensing AW, Matisse Investigators (2003) Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. N Engl J Med 349:1695–1702CrossRefPubMed
31.
Buller HR, Davidson BL, Decousus H, Gallus A, Gent M, Piovella F, Prins MH, Raskob G, Segers AE, Cariou R, Leeuwenkamp O, Lensing AW, Matisse Investigators (2004) Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial. Ann Intern Med 140:867–873PubMed
32.
Eriksson BI, Bauer KA, Lassen MR, Turpie AG, Steering Committee of the Pentasaccharide in Hip-Fracture Surgery Study (2001) Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery. N Engl J Med 345:1298–1304CrossRefPubMed
33.
Eriksson BI, Lassen MR, PENTasaccharide in Hip-FRActure Surgery Plus Investigators (2003) Duration of prophylaxis against venous thromboembolism with fondaparinux after hip fracture surgery: a multicenter, randomized, placebo-controlled, double-blind study. Arch Intern Med 163:1337–1342CrossRefPubMed
34.
Lim W, Dentali F, Eikelboom JW, Crowther MA (2006) Meta-analysis: low-molecular-weight heparin and bleeding in patients with severe renal insufficiency. Ann Intern Med 144:673–684PubMed
35.
Kearon C, Ginsberg JS, Julian JA, Douketis J, Solymoss S, Ockelford P, Jackson S, Turpie AG, MacKinnon B, Hirsh J, Gent M, Fixed-Dose Heparin (FIDO) Investigators (2006) Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism. JAMA 296:935–942CrossRefPubMed
36.
Raschke RA, Reilly BM, Guidry JR, Fontana JR, Srinivas S (1993) The weight-based heparin dosing nomogram compared with a “standard care” nomogram. A randomized controlled trial. Ann Intern Med 119:874–881PubMed
37.
Gawoski JM, Arkin CF, Bovill T, Brandt J, Rock WA Jr, Triplett DA (1987) The effects of heparin on the activated partial thromboplastin time of the College of American Pathologists Survey specimens. Responsiveness, precision, and sample effects. Arch Pathol Lab Med 111:785–790PubMed
38.
Bates SM, Weitz JI, Johnston M, Hirsh J, Ginsberg JS (2001) Use of a fixed activated partial thromboplastin time ratio to establish a therapeutic range for unfractionated heparin. Arch Intern Med 161:385–391CrossRefPubMed
39.
Levine MN, Hirsh J, Gent M, Turpie AG, Cruickshank M, Weitz J, Anderson D, Johnston M (1994) A randomized trial comparing activated thromboplastin time with heparin assays in patients with acute venous thromboembolism requiring large daily doses of heparin. Arch Intern Med 154:49–56CrossRefPubMed
40.
Warkentin TE, Greinacher A, Koster A, Lincoff AM, American College of Chest Physicians (2008) Treatment and prevention of heparin-induced thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest 133:340S–380SCrossRefPubMed
41.
Savi P, Herault JP, Duchaussoy P, Millet L, Schaeffer P, Petitou M, Bono F, Herbert JM (2008) Reversible biotinylated oligosaccharides: a new approach for a better management of anticoagulant therapy. J Thromb Haemost 6:1697–1706CrossRefPubMed
42.
Buller HR, Cohen AT, Davidson B, Decousus H, Gallus AS, Gent M, Pillion G, Piovella F, Prins MH, Raskob GE (2007) Idraparinux versus standard therapy for venous thromboembolic disease. N Engl J Med 357:1094–1104CrossRefPubMed
43.
Buller HR, Cohen AT, Davidson B, Decousus H, Gallus AS, Gent M, Pillion G, Piovella F, Prins MH, Raskob GE (2007) Extended prophylaxis of venous thromboembolism with idraparinux. N Engl J Med 357:1105–1112CrossRefPubMed
44.
Bousser MG, Bouthier J, Buller HR, Cohen AT, Crijns H, Davidson BL, Halperin J, Hankey G, Levy S, Pengo V, Prandoni P, Prins MH, Tomkowski W, Thorp-Pedersen C, Wyse DG (2008) Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomized, open-label non-inferiority trial. Lancet 371:315–321CrossRefPubMed
45.
Weitz JI, Hirsh J, Samama MM, American College of Chest Physicians (2008) New antithrombotic drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest 133:234S–256SCrossRefPubMed
46.
Guertin KR, Choi YM (2007) The discovery of the Factor Xa inhibitor otamixaban: from lead identification to clinical development. Curr Med Chem 14:2471–2481CrossRefPubMed
47.
48.
Sabatine MS, Antman EM, Widimsky P, Ebrahim IO, Kiss RG, Saaiman A, Polasek R, Contant CF, McCabe CH, Braunwald E (2009) Otamixaban for the treatment of patients with non-ST-elevation acute coronary syndromes (SEPIA-AC1 TIMI42): a randomized, double-blind, active-controlled, phase 2 trial. Lancet 374:787–795CrossRefPubMed
49.
Dyke CK, Steinhubl SR, Kleiman NS, Cannon RO, Aberle LG, Lin M, Myles SK, Melloni C, Harrington RA, Alexander JH, Becker RC, Rusconi CP (2006) First-in-human experience of an antidote-controlled anticoagulant using RNA aptamer technology: a phase 1a pharmacodynamic evaluation of a drug-antidote pair for the controlled regulation of factor IXa activity. Circulation 114:2490–2497CrossRefPubMed
50.
Chan MY, Cohen MG, Dyke CK, Myles SK, Aberle LG, Lin M, Walder J, Steinhubl SR, Gilchrist IC, Kleiman NS, Vorchheimer DA, Chronos N, Melloni C, Alexander JH, Harrington RA, Tonkens RM, Becker RC, Rusconi CP (2008) Phase 1b randomized study of antidote-controlled modulation of factor IXa activity in patients with stable coronary artery disease. Circulation 117:2865–2874CrossRefPubMed
51.
Gross PL, Weitz JI (2009) New antithrombotic drugs. Clin Pharmacol Therap 86:139–146CrossRef
Metadata
Title
Update on heparin: what do we need to know?
Authors
Daniel S. Weitz
Jeffrey I. Weitz
Publication date
01-02-2010
Publisher
Springer US
Published in
Journal of Thrombosis and Thrombolysis / Issue 2/2010
Print ISSN: 0929-5305
Electronic ISSN: 1573-742X
DOI
https://doi.org/10.1007/s11239-009-0411-6

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