[The risk of bleeding associated with low molecular weight heparin in patients with renal failure]

Abstract

Cardiovascular mortality and morbidity are higher in patients with chronic renal disease than in the general population. Patients with chronic renal disease are in the highest risk group for thromboembolic disease and many clinical trials have demonstrated the greater safety and efficacy of low-molecular-weight heparin (LMWH) versus unfractionated heparin (UFH). LMWH is cleared only by the kidneys while UFH is cleared by the renal and hepatic routes. Furthermore, LMWH has a significant accumulative effect in patients with impaired renal function (creatinine clearance <30 mL/min). The aim of this study was to evaluate the risk of bleeding when LMWH is used as an anticoagulant in hemodialysis or for treatment of acute thromboembolic disease in patients with renal failure. Twenty-one adult patients were enrolled, 13 with end-stage renal disease requiring chronic hemodialysis and 6 with acute thromboembolic disease and severe renal insufficiency (creatinine clearance <30 mL/min). Group A consisted of 13 patients receiving LMWH (enoxaparin 60 IU/kg/day) for preventing thrombosis of the extracorporeal dialysis circuit. Group B consisted of 8 patients with acute thromboembolic disease receiving LMWH (enoxaparin 60 IU/kg/day). In all patients anti-Xa activity was measured by a chromogenic assay (HEMONOX). In the first group 2 blood samples were taken during the dialysis session (2-4 hours) and a third sample after the end of the session up to 48 hours following enoxaparin injection; in the second group a blood sample was taken 4 days after the start of LMWH treatment, 2 hours after its daily administration. In group A, all dialysis sessions were performed with no minor or major bleeding. Anti-Xa activity was highest 2 hours after the start and remained above 100 seconds after the end of the session, while 44 hours after injection, at the start of the next dialysis session, it was low or absent (<100 seconds). In the second group there were 2 major bleeding episodes, 2 minor bleeding episodes, 1 prolonged time to hemostasis after needle removal, and 2 bleeding episodes at the vascular access site (central venous catheter). Anti-Xa activity was consistently higher than 200 seconds (therapeutic target range:100-200 seconds) and showed interindividual variability (in 2 patients the anti-Xa time was more than 900 seconds), indicating a high risk of bleeding. LMWH seems to be as effective and safe as UFH in terms of bleeding complications and in preventing extracorporeal circuit thrombosis in patients on hemodialysis. Our results indicate that it is preferable to avoid invasive procedures for 12 hours following a dialysis session performed with LMWH anticoagulation because the anticoagulant effect lasted at least 4 hours after its injection. These data suggest that in patients with acute thromboembolic events and severe renal insufficiency, standard anticoagulation with LMWH is not recommended because of an increased risk of major and minor bleeding.