Renal function and thromboprophylaxis in critically ill patients

Robinson and colleagues [1] recently examined the effective dose of enoxaparin for thromboprophylaxis in critically ill patients recorded over 24 hours. The study concluded that the standard dose of 40 mg led to subtherapeutic anti-factor Xa activity (aFXa) and 60 mg daily was optimal. The high rate of thromboembolic disease observed in critically ill patients could thus be explained by inadequate aFXa with the standard 40 mg dose. Low molecular weight heparins (LMWHs) are renally excreted and Robinson and colleagues excluded patients receiving renal replacement therapy as this may have influenced aFXa [1]. Douketis and colleagues [2] documented that excessive anticoagulation did not occur with prophylactic doses of dalteparin in critically ill patients with severe renal impairment. However, in a study of two different prophylactic LMWHs in elderly patients with impaired renal function, enoxaparin but not tinzaparin accumulated over 8 days [3]. The pharmacokinetics of different LMWHs varies [3,4], and excessive anticoagulation over time might occur with a 60 mg daily dose of enoxaparin, especially if renal function is impaired. Perturbations of renal function may also explain why standard dose enoxaparin is subtherapeutic in many critically ill patients [1]. Fuster-Lluch and colleagues [5] reported that 30% of patients show augmented renal clearance during the first week of critical illness. Typically, those with supranormal creatinine clearance were postoperative patients or had sepsis or trauma. This patient group is hypercoagulable and at high risk of thromboembolic disease; however, augmented renal clearance would reduce the effectiveness of LMWHs. The optimal prophylactic dose of LMWHs in critical illness is probably, therefore, best determined by monitoring of aFXa.