Abstract
Background: Current guidelines recommend the monitoring of anti-factor Xa (anti-Xa) levels to avoid an accumulation of low-molecular-weight heparins in patients with acute kidney injury, but there is no evidence on how to proceed with such monitoring during continuous renal replacement therapy. Against this background, we investigated the potential accumulation of enoxaparin administered subcutaneously for venous thromboembolism prophylaxis in critically ill patients during continuous renal replacement therapy covered by regional citrate anticoagulation. Methods: Anti-Xa levels were measured at baseline (≤12 h before renal replacement therapy) and on three consecutive days (A to C) when enoxaparin had reached trough levels. Supplementary testing included modified assays of rotational thromboelastometry known to be highly sensitive for low-molecular-weight heparins. Results: The 16 men and 13 women included were adults comparable in age, body mass index, thromboembolism risk assessment, and clinical severity of the disease. Throughout the four examinations, the median trough levels of anti-Xa remained below the detection limit of the test (<0.1 IU mL−1), with interquartile ranges of <0.1 to 0.14 IU mL−1 at baseline and <0.1 to 0.16 IU mL−1 on days A/B/C. All rotational thromboelastometry parameters of clot initiation and clot formation dynamics did not significantly change from baseline to day C. Conclusions: Neither anti-Xa levels nor modified assays of rotational thromboelastometry revealed any accumulation of enoxaparin administered for thromboprophylaxis during continuous renal replacement therapy covered by regional citrate anticoagulation. Although generally recommended in patients with acute kidney injury, monitoring of anti-Xa levels should be questioned in this defined setting.
Highlights
The delicate hemostatic balance of critically ill patients has been extensively discussed ever since the mid-2000s [1,2]
The finding that median anti-Xa trough levels remained below the detection limit on each of three consecutive continuous renal replacement therapy (CRRT) days was confirmed by observing no significant differences in ROTEM parameters of clot initiation, clot formation dynamics, and clot firmness between baseline and day C
Patients managed by CRRT in the Intensive Care Units (ICUs), even when regional citrate anticoagulation of the extracorporeal circuit is provided as the recommended standard of care, still require venous thromboembolism prophylaxis [5,6]
Summary
The delicate hemostatic balance of critically ill patients has been extensively discussed ever since the mid-2000s [1,2]. Depending on underlying etiologies and therapeutic interventions, patients may present with a hypercoagulable state carrying an increased risk of venous thromboembolism, alternatively be at risk of bleeding, or have both risks at the same time. The latter is true in perioperative settings, as tissue trauma induces procoagulant hemostatic alterations while bleeding prevention is a major requirement after surgery [3,4]. As procoagulatory and proinflammatory processes are activated by extracorporeal circulation, adding to the risk of thromboembolic events and notably of filter clotting, anticoagulation is recommended during CRRT [5] Effective protection of this extracorporeal circuit by regional citrate anticoagulation does not obviate the need for venous thromboembolism prophylaxis [5,6]. Prophylaxis by systemic administration of a lowmolecular-weight heparin (LMWH) as recommended by current guidelines for critically ill patients raises the question of how to avoid an accumulation of this drug [7,8]
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