Thromb Haemost 2009; 101(02): 325-332
DOI: 10.1160/TH08-05-0280
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

How useful is determination of anti-factor Xa activity to guide bridging therapy with enoxaparin?

A pilot study
Christoph Hammerstingl
1   St. Marien Hospital, Bonn, Germany
,
Heyder Omran
1   St. Marien Hospital, Bonn, Germany
,
Christian Tripp
1   St. Marien Hospital, Bonn, Germany
,
Bernd Poetzsch
2   University of Bonn, Bonn, Germany
› Author Affiliations
Further Information

Publication History

Received: 02 May 2008

Accepted after major revision: 22 January 2008

Publication Date:
23 November 2017 (online)

Summary

Low-molecular-weight heparins (LMWH) are commonly used as peri-procedural bridging anticoagulants. The usefulness of measurement of anti-factor Xa activity (anti-Xa) to guide bridging therapy with LMWH is unknown. It was the objective of this study to determine levels of anti-Xa during standard bridging therapy with enoxaparin, and to examine predictors for residual anti-Xa. Consecutive patients receiving enoxaparin at a dosage of 1 mg/kg body weight/12 hours for temporary interruption of phenprocoumon were prospectively enrolled to the study. Blood-samples were obtained 14 hours after LMWH-application immediately pre- procedurally. Procedural details, clinical and demographic data were collected and subsequently analyzed. Seventy patients were included (age 75.2 ± 10.8 years, Cr Cl 55.7 ± 21.7ml/min, body mass index [BMI] 27.1 ± 4.9). LMWH- therapy was for a mean of 4.2 ± 1.6 days; overall anti-Xa was 0.58 ± 0.32 U/ml. In 37 (52.8%) of patients anti-Xa was ≥0.5 U/ml, including 10 (14.3%) patients with anti-Xa > 1U/ml. Linear regression analysis of single variables and logistic multivariable regression analysis failed to prove a correlation between anti-Xa and single or combined factors. No major bleeding, no thromboembolism and four (5.7%) minor haemorrhages were observed. When bridging OAC with therapeutic doses of enoxaparin a high percentage of patients undergo interventions with high residual anti-Xa. The levels of anti-Xa vary largely and are independent of single or combined clinical variables. Since the anti-Xa-related outcome of patients receiving bridging therapy with LMWH is not investigated, no firm recommendation on the usefulness of monitoring of anti-Xa can be given at this stage.

 
  • References

  • 1 Ansell J, Hirsh J, Hylek E. et al. Pharmacology and Management of the Vitamin K Antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133 Suppl 160S-198.
  • 2 Douketis JD, Berger PB, Dunn AS. et al. The Peri-operative Management of Antithrombotic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133 (Suppl. 06) 299S-339.
  • 3 Dunn AS, Turpie AG. Perioperative management of patients receiving oral anticoagulants: a systematic review. Arch Intern Med 2003; 163: 901-908.
  • 4 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. 01) 64S-94S.
  • 5 Douketis JD, Crowther MA, Cherian SS. et al. Physician preferences for perioperative anticoagulation in patients with a mechanical heart valve who are undergoing elective noncardiac surgery. Chest 1999; 116: 1240-1246.
  • 6 Weitz JI. Low-molecular-weight heparins. N Engl J Med 1997; 337: 688-698.
  • 7 Spyropoulos AC, Bauersachs RM, Omran H. et al. Periprocedural bridging therapy in patients receiving chronic oral anticoagulation therapy. Curr Med Res Opin 2006; 22: 1109-1122.
  • 8 Jaffer AK, Ahmed M, Brotman DJ. et al. Low-molecular-weight-heparins as periprocedural anticoagulation for patients on long-term warfarin therapy: a standardized bridging therapy protocol. J Thromb Thrombolysis 2005; 20: 11-16.
  • 9 Douketis JD. Perioperative anticoagulation management in patients who are receiving oral anticoagulant therapy: a practical guide for clinicians. Thromb Res 2002; 108: 3-13.
  • 10 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. 01) 64S-94S.
  • 11 Weitz JI. Low-molecular-weight heparins. N Engl J Med 1997; 337: 688-698.
  • 12 Hammerstingl C, Tripp C, Schmidt H. et al. Peri-procedural bridging therapy with low-molecular-weight heparin in chronically anticoagulated patients with prosthetic mechanical heart valves: experience in 116 patients from the prospective BRAVE registry. J Heart Valve Dis 2007; 16: 285-292.
  • 13 Douketis JD, Johnson JA, Turpie AG. Low-molecular-weight heparin as bridging anticoagulation during interruption of warfarin: assessment of a standardized periprocedural anticoagulation regimen. Arch Intern Med 2004; 164: 1319-1326.
  • 14 Ferreira I, Dos L, Tornos P. et al. Experience with enoxaparin in patients with mechanical heart valves who must withhold acenocumarol. Heart 2003; 89: 527-530.
  • 15 Spandorfer JM, Lynch S, Weitz HH. et al. Use of enoxaparin for the chronically anticoagulated patient before and after procedures. Am J Cardiol 1999; 84: 478-480 A10.
  • 16 Fuster V, Ryden LE, Cannom DS. et al. ACC/AHA/ ESC 2006 guidelines for the management of patients with atrial fibrillation: full text: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 guidelines for the management of patients with atrial fibrillation) developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Europace 2006; 8: 651-745.
  • 17 O’Donnell MJ, Kearon C, Johnson J. et al. Brief communication: Preoperative anticoagulant activity after bridging low-molecular-weight heparin for temporary interruption of warfarin. Ann Intern Med 2007; 146: 184-187.
  • 18 Douketis JD, Woods K, Foster GA. et al. Bridging anticoagulation with low-molecular-weight heparin after interruption of warfarin therapy is associated with a residual anticoagulant effect prior to surgery. Thromb Haemost 2005; 94: 528-531.
  • 19 Kovacs MJ, Levine MN, Keeney M. et al. Anti-Xa effect of a low molecular weight heparin (dalteparin) does not accumulate in extended duration therapy for venous thromboembolism in cancer patients. Thromb Haemost 2005; 93: 1185-1188.
  • 20 Kitchen S, Iampietro R, Woolley AM. et al. Anti Xa monitoring during treatment with low molecular weight heparin or danaparoid: inter-assay variability. Thromb Haemost 1999; 82: 1289-1293.
  • 21 Mismetti P, Laporte-Simitsidis S, Navarro C. et al. Aging and venous thromboembolism influence the pharmacodynamics of the anti-factor Xa and anti-thrombin activities of a low molecular weight heparin (nadroparin). Thromb Haemost 1998; 79: 1162-1165.
  • 22 Bounameaux H, De MP. Is laboratory monitoring of low-molecular-weight heparin therapy necessary? No. J Thromb Haemost 2004; 2: 551-554.
  • 23 Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31-41.
  • 24 Levey AS, Coresh J, Balk E. et al. Definition and classification of stages of chronic kidney disease. Am J Kidney Dis 2002; 39: S46-S75.
  • 25 Dolovich LR, Ginsberg JS, Douketis JD. et al. 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 2000; 160: 181-188.
  • 26 Douketis JD, Johnson JA, Turpie AG. Low-molecular-weight heparin as bridging anticoagulation during interruption of warfarin: assessment of a standardized periprocedural anticoagulation regimen. Arch Intern Med 2004; 164: 1319-1326.
  • 27 Dunn AS, Spyropoulos AC, Turpie AG. Bridging therapy in patients on long-term oral anticoagulants who require surgery: the Prospective Peri-operative Enoxaparin Cohort Trial (PROSPECT). J Thromb Haemost 2007; 5: 2211-2218.
  • 28 Kovacs MJ, Kearon C, Rodger M. et al. Single-arm study of bridging therapy with low-molecular-weight heparin for patients at risk of arterial embolism who require temporary interruption of warfarin. Circulation 2004; 110: 1658-1663.
  • 29 Omran H, Hammerstingl C, Paar WD. Perioperative bridging with enoxaparin. Results of the prospective BRAVE registry with 779 patients. Med Klin (Munich) 2007; 102: 809-815.
  • 30 Rivas-Gandara N, Ferreira-Gonzalez I, Tornos P. et al. Enoxaparin as bridging anticoagulant treatment in cardiac surgery. Heart 2008; 94: 205-210.
  • 31 Spyropoulos AC, Turpie AG, Dunn AS. et al. Clinical outcomes with unfractionated heparin or low-molecular-weight heparin as bridging therapy in patients on long-term oral anticoagulants: the REGIMEN registry. J Thromb Haemost 2006; 4: 1246-1252.
  • 32 Omran H, Hammerstingl C, Schmidt H. et al. A prospective and randomized comparison of the safety and effects of therapeutic levels of enoxaparin versus unfractionated heparin in chronically anticoagulated patients undergoing elective cardiac catheterization. Thromb Haemost 2003; 90: 267-271.
  • 33 Dupont WD, Plummer D. PS power and sample size program available for free on the internet. Controlled Clinical Trials 1997; 18: 274.
  • 34 Becker RC, Spencer FA, Gibson M. et al. Influence of patient characteristics and renal function on factor Xa inhibition pharmacokinetics and pharmacodynamics after enoxaparin administration in non-ST-segment elevation acute coronary syndromes. Am Heart J 2002; 143: 753-759.
  • 35 Despotovic N, Erceg P, Nikolic-Despotovic M. et al. Bleeding during enoxaparin treatment more common with age over 75 years and severe renal insufficiency. Drugs Aging 2007; 24: 777-779.
  • 36 Hulot JS, Montalescot G, Lechat P. et al. Dosing strategy in patients with renal failure receiving enoxaparin for the treatment of non-ST-segment elevation acute coronary syndrome. Clin Pharmacol Ther 2005; 77: 542-552.
  • 37 Hulot JS, Vantelon C, Urien S. et al. Effect of renal function on the pharmacokinetics of enoxaparin and consequences on dose adjustment. Ther Drug Monit 2004; 26: 305-310.
  • 38 Kruse MW, Lee JJ. Retrospective evaluation of a pharmacokinetic program for adjusting enoxaparin in renal impairment. Am Heart J 2004; 148: 582-589.
  • 39 Nagge J, Fernandes O, Huh J. Evaluation of a pharmacokinetic program for adjusting enoxaparin in renal impairment. Am Heart J 2005; 149: e21-e24.
  • 40 Veiga F, Escriba A, Maluenda MP. et al. Low molecular weight heparin (enoxaparin) versus oral anticoagulant therapy (acenocoumarol) in the long-term treatment of deep venous thrombosis in the elderly: a randomized trial. Thromb Haemost 2000; 84: 559-564.
  • 41 Nieuwenhuis HK, Albada J, Banga JD. et al. Identification of risk factors for bleeding during treatment of acute venous thromboembolism with heparin or low molecular weight heparin. Blood 1991; 78: 2337-2343.