Bridging of oral anticoagulation with low-molecular-weight heparin: Experience in 373 patients with renal insufficiency undergoing invasive procedures

Summary

If surgery or another intervention is planned, current guidelines recommend bridging oral anticoagulation (OAC) with heparins in patients at elevated thromboembolic (TE) risk. While patients with renal impairment have a higher risk of bleeding and dosing of heparins is more difficult, there are no specific recommendations for bridging the latter patients. Hence, we aimed to investigate the efficacy and tolerability of using reduced low-molecular-weight heparin (enoxaparin) dosages for bridging of OAC. Three hundred twenty-two hospitalised and 51 ambulatory adult patients at moderate to high TE risk were enrolled. Patients with renal insufficiency (n=274 with creatinine clearance [CrCl] 30–50 ml/min and n=99 with CrCl 20–29 ml/min) received after discontinuation of OAC therapy enoxaparin 1mg/ kg once daily. Surgery was performed at international normalised ratio (INR) <1.5. Mean time between the last enoxaparin dose and procedure was 26.8 ± 2.7 hours. Within 30 days of individual follow-up, no case of TE was observed (0 %; 95 % confidence interval [CI] 0– 0.9). A total of 30 bleeding events (8.0 %; CI 5.5–11.3) occurred (3 major [0.8 %; CI 0.2–2.3] and 27 minor [7.2 %; CI 4.8–10.4]). Bleeding events occurred in 6.5% (CI 3.9–10.2) of patients with CrCl 30–50 ml/min and in 12.1% (CI 6.4–20.2) of patients with CrCl 20–29 ml/min (p between groups =0.08). Logistic regression analysis identified the CHADS₂ score as the only independent haemorrhagic risk factor (p= 0.03). No heparin-induced thrombocytopenia (HIT-II) was reported. Bridging therapy could be performed in 51 (13.7%) ambulatory patients. In renally impaired patients undergoing bridging of OAC, the use of a priori reduced dosage of enoxaparin was not compromised by any TE events. It appeared well tolerated as the rate of major bleeds was low.

Keywords

Perioperative management - anticoagulation - low-molecular-weight heparin - thrombosis - bleeding - stratification - surgery - bridging - enoxaparin - register

• References

• 1 Spyropoulos AC. Bridging of oral anticoagulation therapy for invasive procedures.. Curr Hematol Rep 2005; 4: 405-413.
• 2 Coresh J. et al. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey.. Am J Kidney Dis 2003; 41: 1-12.
• 3 Elsayed EF. et al. Cardiovascular Disease and Subsequent Kidney Disease.. Arch Intern Med 2007; 167: 1130-1136.
• 4 Freedman BI, DuBose TD. Jr. Chronic kidney disease: Cause and consequence of cardiovascular disease.. Arch Intern Med 2007; 167: 1113-1115.
• 5 National Kidney Foundation.. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification.. Updated 2002. Available at: http://www.kidney.org/professionals/kdoqi/guidelines_ckd/toc.htm Accessed on 26. September 2008.
• 6 Douketis JD. et al. The Perioperative Management of Antithrombotic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Ed.).. Chest 2008; 133: 299S-339.
• 7 Lim W. et al. Meta-analysis: low-molecular-weight heparin and bleeding in patients with severe renal insufficiency.. Ann Intern Med 2006; 144: 673-684.
• 8 Spyropoulos AC. et al. Periprocedural bridging therapy in patients receiving chronic oral anticoagulation therapy.. Curr Med Res Opin 2006; 22: 1109-1122.
• 9 Kruse MW, Lee JJ. Retrospective evaluation of a pharmacokinetic program for adjusting enoxaparin in renal impairment.. Am Heart J 2004; 148: 582-589.
• 10 Collet JP. et al. Enoxaparin in unstable angina patients with renal failure.. Int J Cardiol 2001; 80: 81-82.
• 11 Omran H. et al. Perioperative bridging with enoxaparin. Results of the prospective BRAVE registry with 779 patients.. Med Klin (Munich) 2007; 102: 809-815.
• 12 Hammerstingl C. et al. Periprocedural 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 Singer DE. et al. Antithrombotic Therapy in Atrial Fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Ed.).. Chest 2008; 133: 546S-592.
• 14 Singer DE. et al. Antithrombotic therapy in atrial fibrillation: the Seventh ACCP Conference on Anti-thrombotic and Thrombolytic Therapy.. Chest 2004; 126: 429S-456S.
• 15 Jovanovic BD, Zalenski RJ. Safety evaluation and confidence intervals when the number of observed events is small or zero.. Ann Emerg Med 1997; 30: 301-306.
• 16 Gage BF. et al. Validation of clinical classification schemes for predicting stroke: Results from the National Registry of Atrial Fibrillation.. J Am Med Assoc 2001; 285: 2864.
• 17 Hirsh J. et al. Antithrombotic and thrombolytic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Ed.).. Chest 2008; 133: 110S-112S.
• 18 Hirsh J. et al. Parenteral Anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Ed.).. Chest 2008; 133: 141S-159.
• 19 Spyropoulos AC. 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.
• 20 Mahe I. et al. Tinzaparin and enoxaparin given at prophylactic dose for eight days in medical elderly patients with impaired renal function: a comparative pharmacokinetic study.. Thromb Haemost 2007; 97: 581-586.
• 21 Hammerstingl C. et al. How useful is determination of anti factor Xa activity to guide bridging therapy with enoxaparin? A Pilot Study.. Thromb Haemost 2009; 101: 325-332.
• 22 Ma JM. et al. Anti-Xa monitoring of enoxaparin for acute coronary syndromes in patients with renal disease.. Ann Pharmacother 2004; 38: 1576-1581.
• 23 Berges A. et al. Anti-factor Xa activity of enoxaparin administered at prophylactic dosage to patients over 75 years old.. Br J Clin Pharmacol 2007; 64: 428-438.
• 24 Green B. et al. Dosing strategy for enoxaparin in patients with renal impairment presenting with acute coronary syndromes.. Br J Clin Pharmacol 2005; 59: 281-290.
• 25 Hulot JS. 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.
• 26 Sanderink GJ. et al. Pharmacokinetics and pharmacodynamics of the prophylactic dose of enoxaparin once daily over 4 days in patients with renal impairment.. Thromb Res 2002; 105: 225-231.
• 27 Schuck O. et al. Predicting the glomerular filtration rate from serum creatinine, serum cystatin C and the Cockcroft and Gault formula with regard to drug dosage adjustment.. Int J Clin Pharmacol Ther 2004; 42: 93-97.
• 28 Bazinet A. et al. Dosage of enoxaparin among obese and renal impairment patients.. Thromb Res 2005; 116: 41-50.
• 29 Bick RL, Fareed J. Low molecular weight heparins: differences and similarities in approved preparations in the United States.. Clin Appl Thromb Hemost 1999; 5 (01) S63-6.
• 30 Ofosu FA. Differences in the safety profiles of two low-molecular-weight heparins.. Thromb Haemost 2008; 99: 989-990.
• 31 Omran 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.