Thromb Haemost 2000; 84(01): 22-26
DOI: 10.1055/s-0037-1613961
Commentary
Schattauer GmbH

Nomograms for the Administration of Unfractionated Heparin in the Initial Treatment of Acute Thromboembolism – an Overview

Enrico Bernardi
2   From the Department of Medical and Surgical Sciences, 2nd Chair of Internal Medicine, Padua, Italy
,
Andrea Piccioli
1   The Division of Pneumology, Chair of Pulmonary Medicine, University of Padua, Padua, Italy
,
Giancarlo Oliboni
1   The Division of Pneumology, Chair of Pulmonary Medicine, University of Padua, Padua, Italy
,
Renzo Zuin
1   The Division of Pneumology, Chair of Pulmonary Medicine, University of Padua, Padua, Italy
,
Antonio Girolami
2   From the Department of Medical and Surgical Sciences, 2nd Chair of Internal Medicine, Padua, Italy
,
Paolo Prandoni
2   From the Department of Medical and Surgical Sciences, 2nd Chair of Internal Medicine, Padua, Italy
› Author Affiliations
Further Information

Publication History

Received 11 August 1999

Accepted after resubmission 29 February 2000

Publication Date:
10 December 2017 (online)

Summary

Despite the availability of low-molecular-weight heparins, unfractionated heparin (UFH) still remains the drug of choice for the initial treatment of acute venous thromboembolism in many countries. When appropriately employed, UFH treatment results in a degree of efficacy and safety that is fully comparable with that obtained with the use of heparin derivatives. The use of nomograms for the intravenous or subcutaneous administration of UFH assures that virtually all patients will promptly achieve adequate levels of anticoagulation, thus decreasing the likelihood of recurrent venous thromboembolism without extra bleeding-risk.

In this article we reviewed clinical studies on the implementation and validation of UFH dosing nomograms, and attempted a quantitative analysis of their performance. According to the results of our analysis, a statistically significantly higher proportion of patients treated on the basis of a nomogram reached a therapeutic anticoagulant level within 24 h of treatment, as compared to patients treated following the standard practice (odds ratio, 3.6; 95% CI, 2.6 to 4.9). The rate of recurrent thromboembolic events was significantly lower for patients treated according to a nomogram (odds ratio, 0.3; 95% CI, 0.1 to 0.8), while no significant differences in terms of either major or minor bleedings were detected between nomogram patients and controls.

 
  • References

  • 1 Lensing AWA, Prandoni P, Prins MH, Bullar HR. Deep-vein thrombosis. Lancet 1999; 353: 479-85.
  • 2 Hirsh J, Raschke R, Warkentin TE, Dalen JE, Deykin D, Poller L. Heparin and low-molecular-weight heparin: mechanism of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest 1998; 114: 489s-510s.
  • 3 Brandjes DPM, Heijboer H, Buller HR, De Rijk M, Jagt H, ten Cate JW. Acemocumarol and heparin compared with acenocumarol alone in the initial treatment of proximal-vein thrombosis. N Engl J Med 1992; 327: 1485-9.
  • 4 1999 Update: ACC/AHA guidelines for the management of patients with acute myocardial infarction. A report of the American college of cardiology/American heart association task force on practice guidelines (committee on management of acute myocardial infarction). J Am Coll Card 1999; 34: 890-911.
  • 5 Basu D, Gallus A, Hirsh J, Cade J. A prospective study of the value of monitoring heparin treatment with the activated partial thromboplastin time. N Engl J Med 1972; 287: 324-7.
  • 6 Reilly BM, Raschke RA, Srinivas S, Nieman T. Intravenous heparin dosing patterns and variations in internists’ practices. J Gen Intern Med 1993; 08: 536-42.
  • 7 Saya FG, Coleman LT, Martinoff JT. Pharmacist-directed heparin therapy using a standard dosing and monitoring protocol. Am J Hosp Pharm 1985; 42: 1965-69.
  • 8 Fennerty AG, Renowden S, Scolding N, Bentley DP, Campbell IA, Routledge PA. Guidelines to control heparin treatment. Brit Med J 1986; 292: 579-80.
  • 9 Cruickshank MK, Levine MN, Hirsh J, Roberts R, Siguenza M. A standard heparin nomogram for the management of heparin therapy. Arch Intern Med 1991; 151: 333-7.
  • 10 Hull RD, Raskob GE, Rosenbloom D, Lemaire J, Pineo GF, Baylis B, Ginsberg JS, Panju AA, Brill-Edwards P, Brant R. Optimal therapeutic level of heparin therapy in patients with venous thrombosis. Arch Intern Med 1992; 152: 1589-95.
  • 11 Raschke RA, Reilly BM, Guidry JR, Fontana JR, Srinivas S. The weightbased heparin dosing nomogram compared with a “standard care” nomogram. A randomized controlled trial. Ann Intern Med 1993; 119: 874-81.
  • 12 Elliott GC, Hiltunen SJ, Suchyta M, Hull RD, Raskob GE, Pineo GF, Jensen RL, Yeates S, Kitterman N. Physician-guided treatment compared with a heparin protocol for deep vein thrombosis. Arch Intern Med 1994; 154: 999-1004.
  • 13 Levine MN, Hirsh J, Gent M, Turpie AG, Cruickshank M, Weitz J, Anderson D, Johnson M. A randomized trial comparing activated thromboplastin time with heparin assay in patients with acute venous thromboembolism requiring large daily doses of heparin. Arch Intern Med 1994; 154: 49-56.
  • 14 Rivey MP, Peterson JP. Pharmacy-managed, weight-based heparin protocol. Am J Hosp Pharm 1993; 50: 279-84.
  • 15 Hollingsworth JA, Rowe BH, Brisebois FJ, Thompson PA, Fabris LM. The successful application of a heparin nomogram in a community hospital. Arch Intern Med 1995; 155: 2095-100.
  • 16 Raschke RA, Gollihare B, Pierce JC. The effectiveness of implementing the weight-based heparin nomogram as a practice guideline. Arch Intern Med 1996; 156: 1645-9.
  • 17 Kershaw B, White RH, Mungall D, Van Houten J, Brettfeld S. Computer assisted dosing of heparin. Management with a pharmacy-based anticoagulation service. Arch Intern Med 1994; 154: 1005-11.
  • 18 Brown G, Dodek P. An evaluation of empiric vs. nomogram-based dosing of heparin in an intensive care unit. Crit Care Med 1997; 25: 1534-8.
  • 19 Gunnarsson PS, Sawyer WT, Montague D, Williams ML, Dupuis RE, Caiola SM. Appropriate use of heparin, empiric vs nomogram-based dosing. Arch Intern Med 1995; 155: 526-32.
  • 20 de Groot MR, Büller HR, ten Cate JW, van Marwijk Kooy M. Use of a heparin nomogram for treatment of Patients with venous thromboembolism in a community hospital. Thromb Haemost 1998; 80: 70-3.
  • 21 Becker RC, Ball RN, Eisenberg P, Borzak S, Held AC, Spencer F, Voyce SJ, Jesse R, Hendel R, Ma Y, Hurley T, Hebert J. for the Antithrombotic Theraphy Consortium Investigators. A randomised multicenter trial of weight-adjusted intravenous heparin dose titration and point-of-care coagulation monitoring in hospitalised patients with active thromboembolic disease. Am Heart J 1999; 137: 59-71.
  • 22 Prandoni P, Bagatella P, Bernardi E, Girolami B, Rossi L, Scarano L, Marchiori A, Piccioli A, Girolami A. Use of an algorithm for administering subcutaneous heparin in the treatment of deep venous thrombosis. Ann Intern Med 1998; 129: 299-302.
  • 23 Hull RD, Raskob GE, Brant RF, Pineo GF, Valentine KA. The importance of initial heparin treatment on long-term clinical outcomes of antithrombotic therapy. The emerging theme of delayed recurrence. Arch Intern Med 1997; 157: 2317-21.
  • 24 Hull RD, Raskob GE, Brant RF, Pineo GF, Valentine KA. Relation between the time to achieve the lower limit of the APTT therapeutic range and recurrent venous thromboembolism during heparin treatment for deep vein thrombosis. Arch Intern Med 1997; 157: 2562-8.
  • 25 Anand S, Ginsberg JS, Kearon C, Gent M, Hirsh J. The relation between the activated partial thromboplastin time response and recurrence in patients with venous thrombosis treated with continuos intravenous heparin. Arch Intern Med 1996; 156: 1677-81.
  • 26 Anand SS, Bates S, Ginsberg JS, Levine M, Buller H, Prins M, Haley S, Kearon C, Hirsh J, Gent M. Recurrent venous thrombosis and heparin therapy: an evaluation of the importance of early activated partial thromboplastin times. Arch Intern Med 1999; 27: 2029-32.
  • 27 Gould MK, Dembitzer AD, Doyle RL, Hastie TJ, Garber AM. Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep vein thrombosis. A meta-analysis of randomized controlled trials. Ann Intern Med 1999; 130: 800-9.
  • 28 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: 677-81.
  • 29 The Columbus Investigators. Low-molecular-weight heparin in the treatment of patients with venous thromboembolism. N Engl J Med 1997; 337: 657-62.
  • 30 Simonneau G, Sors H, Charbonnier B, Page Y, Laaban JP, Azarian R, Laurent M, Hirsch JL, Ferrari E, Bosson JL, Mottier D, Beau B. for the Thésée Study. A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism. N Engl J Med 1997; 337: 663-9.
  • 31 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. 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: 682-7.
  • 32 Baker BA, Adelman MD, Smith PA, Osborn JC. Inability of the activated partial thromboplastin time to predict heparin levels. Time to reassess guidelines for heparin assays. Arch Intern Med 1997; 157: 2475-9.
  • 33 Brill-Edwards P, Ginsberg JS, Johnston M, Hirsh J. Establishing a therapeutic range for heparin therapy. Ann Intern Med 1993; 119: 104-9.