Enoxaparin Outcomes in Patients With Moderate Renal Impairment | Clinical Pharmacy and Pharmacology | JAMA Internal Medicine | JAMA Network
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    2 Comments for this article
    Which kind of major bleeding?
    Andrea Salvi | Internal Medicine, Ospedale Civile di Brescia, Italy

    It would be very interesting to know the kind of major bleeding observed in patients submitted to bridging therapy. Is the observed bleeding related to the invasive procedure? And if so, was the last dose of enoxaparine stopped at least 24 hours before the procedure? And how many hours after the procedure has the enoxaparine been reassumed?  

    Which kind of major bleeding?
    Douglas DeCarolis | Minneapolis VA Health Care System

    Dr. Salvi,  

    Thank you for your interest and questions. Major bleeding was defined as a bleed causing hospital admission, prolonged hospital stay, or need for emergency room visit/medical attention. Almost all of bleeds in the bridge cohort were related to the the procedure. The majority were related to cardiac procedures (i.e., atrial arrhythmia ablation, coronary angiography, coronary intervention). The types of bleeding relating to these procedures scaled from hematoma at puncture sites to retroperitineal, intraabdominal, and pelvic bleeding (with rectal sheath hematoma). We also observed 3 gastrointestinal/rectal bleeds requiring medical attention after colonoscopy and from surgical
    sites post surgery. 

    Regarding the time period between the last pre-intervention and first post-intervention enoxaparin dose, the Minneapolis VAHCS has an active anticoagulation clinic that protocolizes this transition. Patients are instructed to take the last dose of enoxaparin on the morning 1 day prior to scheduled procedure and to restart on the day (morning) after the procedure. 

    Douglas DeCarolis

    Original Investigation
    Dec 10/24, 2012

    Enoxaparin Outcomes in Patients With Moderate Renal Impairment

    Author Affiliations

    Author Affiliations: Pharmacy Service (Drs DeCarolis, Thorson, Clairmont, and Leuthner), Center for Chronic Disease Outcomes Research (Dr Rector), and Hematology/Oncology Section (Dr Johnson), Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota.

    Arch Intern Med. 2012;172(22):1713-1718. doi:10.1001/2013.jamainternmed.369

    Background Enoxaparin sodium has predictable pharmacokinetics that allow for simplified dosing without laboratory monitoring. Reliance on renal function for excretion may lead to accumulation of enoxaparin in patients with moderate renal impairment. However, there is no dose adjustment recommended for these patients. We conducted a review to compare bleeding events in patients with moderate renal impairment compared with those with normal renal function.

    Methods Patients received enoxaparin sodium, 1 mg/kg, every 12 hours or 1.5 mg/kg once daily between June 1 and November 30, 2009. Moderate renal impairment was defined as creatinine clearance (CrCl) of 30 to 50 mL/min. Normal renal function was defined as CrCl greater than 80 mL/min. The primary outcome was major bleeding, defined as any bleeding resulting in death, hospital admission, lengthened hospital stay, or an emergency department visit. The secondary outcome was thromboembolism.

    Results A total of 164 patients met the inclusion criteria: 105 with normal renal function and 59 with moderate renal impairment. The primary outcome occurred in 6 of 105 patients (5.7%) with normal renal function vs 13 of 59 patients (22.0%) with moderate renal impairment, representing an unadjusted odds ratio of 4.7 (95% CI, 1.7-13.0; P = .002). The odds ratio using multivariable logistic regression adjusting for differences in risk was 3.9 (95% CI, 0.97-15.6; P = .055). There was no recurrent thromboembolism in either group.

    Conclusions Our results suggest an increased risk of major bleeding in patients with moderate renal impairment who receive enoxaparin. Because enoxaparin is frequently used and outcomes can be life saving or life threatening, we encourage further study of the appropriate dose in patients with moderate renal impairment.