Hemorrhagic Complications in Patients Treated with Anticoagulant Doses of a Low Molecular Weight Heparin (Enoxaparin) in Routine Hospital Practice

Abstract

Low molecular weight heparins (LMWHs) are a rapidly growing class of anticoagulant drug. Their efficacy has been demonstrated in several clinical settings where they are rapidly becoming the anticoagulant of choice. Controlled clinical studies in patients with deep vein thrombosis, pulmonary embolism, and unstable angina have documented that the frequency of major hemorrhage is 0.5-4%. The purpose of the study was to determine the frequency of minor and major hemorrhage occurring in patients receiving anticoagulant doses of an LMWH (enoxaparin) during routine clinical practice. A prospective, observational study of consecutive patients receiving enoxaparin 1 mg/kg twice daily for at least 24 hours in five internal medicine wards of a university teaching hospital was performed. Five hundred forty-nine patients were studied. The mean age was 67.5+/-15.5 years and the mean duration of enoxaparin therapy was 3.8+/-1.5 days. Hemorrhage was documented in a total of 94 patients (17.3%). Major hemorrhage occurred in 14 patients (2.6%), injection-site hemorrhage occurred in 55 patients (10%), and minor hemorrhage (noninjection site) was documented in 25 patients (4.7%). There were two deaths attributed to hemorrhage. Patients with major hemorrhage were older than patients with minor or no hemorrhage (75.5+/-10.4 versus 66.8+/-15.2 years; p=0.03) and occurred in patients receiving enoxaparin for a longer period (5.14+/-3.8 days) than those with minor (4+/-2.5 days) or no hemorrhage (2.9+/-2.1 days). Major hemorrhage was significantly associated with impaired renal function, chronic liver disease, and concomitant treatment with warfarin or a proton pump inhibitor. Enoxaparin used in anticoagulant doses in unselected medical patients is not associated with more major hemorrhagic complications than observed in controlled clinical trials. Major hemorrhage may be more likely in older patients, in patients with chronic liver disease and impaired renal function, in patients receiving prolonged enoxaparin therapy, and in patients receiving warfarin or proton pump inhibitors.

Potent Anticoagulants are Associated with a Higher All-Cause Mortality Rate After Hip and Knee Arthroplasty

“…Moreover, because anticoagulation carries a risk of fatal bleeding complications [13,22], all-cause mortality appears a more appropriate marker for comparison because mortality incorporates all cost-benefit effects of prophylaxis.…”

The appropriateness of enoxaparin use in Lebanese hospitals: a quality evaluation study

“…This can be explained by the fact that patients who experienced bleeding events with low doses appeared to have at least one risk factor for bleeding: age [75 years (50%), an abnormal prothrombin time (12.5%), a baseline platelet count \100 9 10 3 /mm 3 (25%), CrCl \30 ml/min (37.5%), anemia (37.5%) and co-administration of other anticoagulants such as aspirin and clopidogrel (50%). Similar risk factors for bleeding in patients receiving enoxaparin were identified in two observational studies [30,38,39]. Since higher anti-Xa levels correlate with increased risk of major bleeding in dose-investigating studies [40], monitoring of anti-Xa levels can improve the safety of enoxaparin especially in patients at risk of bleeding [41].…”

“…Spicer et al [36] demonstrated that weight estimation results in inaccurate dosing in 51% of cases because of the tendency to overestimate the weight of lighter patients and underestimate it in heavier patients [37]. The most important side effect of anticoagulant therapy is bleeding [38] which occurred in 23 patients (5%) with the highest rate observed in the VTE prophylaxis group and patients taking the lower inappropriate doses. This can be explained by the fact that patients who experienced bleeding events with low doses appeared to have at least one risk factor for bleeding: age [75 years (50%), an abnormal prothrombin time (12.5%), a baseline platelet count \100 9 10 3 /mm 3 (25%), CrCl \30 ml/min (37.5%), anemia (37.5%) and co-administration of other anticoagulants such as aspirin and clopidogrel (50%).…”

Inhibition of extrinsic hemostasis activation by low-molecular-weight heparin

“…LMWHs might also be overdosed, however, resulting in severe bleeding complications [21][22][23][24][25][26][27][28]. The plasmatic LMWH action should therefore be monitored especially for renal-insufficient patients [29,30], pregnant patients [31][32][33], patients with abnormal body weight [34], children [35], or patients with high risk of bleeding or thrombosis [1].…”