Competing interestsThe author declares that they have no competing interests.NotesSee related research by Pelekanou et al., http://ccforum.com/content/13/6/R172
Acute Vorinostat IC50 kidney injury (AKI) is a severe complication of critical illness, generally developing as a component of multiple organ failure. If renal replacement therapy is required, continuous techniques are often preferred especially in patients with instable circulation. To prevent clotting in the extracorporeal circuit, continuous anticoagulation is needed and heparins are the classic choice. Both unfractionated heparin and low molecular weight heparins (LMWHs) are used. LMWHs have the advantage that their pharmacokinetics are more predictable due to less binding to proteins and cells [1]. Their clearance is, however, slower.

In addition, renal insufficiency increases half-life of smaller heparin fragments resulting in accumulation of anti-Xa activity, but not of anti-IIa activity [2,3]. Bleeding complications increase when glomerular filtration rate falls below 30 ml/min. The biological activity and behavior of LMWHs during continuous renal replacement therapy is still controversial. Although a previous study found no elimination of LMWHs [4], a recent small study using enoxaparin reported partial removal of anti-Xa activity by filtration and dialysis [5].Hemostatic changes during continuous renal replacement therapy in the critically ill are complex due to simultaneous pro- and anticoagulant processes. Routine prothrombin time (PTT) and activated partial thromboplastin time (aPTT) assays monitor clot formation but are insensitive to hypercoagulant states, especially during anticoagulation.

Plasma anti-Xa activity measures anticoagulant activity of LMWHs. The endogenous thrombin potential (ETP) reflects thrombin generation beyond the initiation of clot formation and may be more informative with regard to the presence of an anti- or procoagulant state [6].The aim of this explorative study in patients with AKI receiving the LMWH nadroparin for anticoagulation of the continuous venovenous hemofiltration (CVVH) circuit was to determine whether anti-Xa activity accumulates, whether it is removed by filtration, and to determine whether ETP could have a role in monitoring hemostasis and circuit clotting. As heparins are a heterogenic mixture of molecules, drug concentrations cannot be measured directly.

We therefore assessed its anticoagulant activity (anti-Xa), which is its clinically relevant effect.Materials Anacetrapib and methodsStudy design and settingThis prospective randomized cross-over trial was conducted in a 20-bed closed format general intensive care unit (ICU) of a teaching hospital. CVVH is the only renal replacement modality used in the unit and is performed under responsibility of the intensivists. Nadroparin is the standard anticoagulant for CVVH in patients without an increased risk of bleeding.