Impact of Continuous Veno-venous Hemodiafiltration on Efficacy of Administration of Prophylactic Doses of Enoxaparin or Fondaparinux in Critically Ill Patients.

Impact of Continuous Veno-venous Hemodiafiltration on Efficacy of Administration of Prophylactic Doses of Enoxaparin or Fondaparinux in Critically Ill Patients.

Dose of anticoagulant prophylaxis in patients with continuous veno-venous hemodiafiltration may be insufficient to keep anti-Xa factor activity in prophylactic range.

Coagulation disorders are one of the most common complications in critically ill patients. Among them deep vein thrombosis and pulmonary embolism are the most significant factors increasing morbidity and mortality in ICU patients. Use of anticoagulant prophylaxis aims to prevent these dangerous complications. Most commonly used anticoagulant prophylaxis agents are low molecular weight heparins (LMWH). LMWH therapeutic efficiency is measured with activity of anti-Xa factor, that should range between 0.2 and 0.4 IU/mL in order to prevent thrombotic complications. Due to grave general condition, critically ill patients may often develop acute kidney injury (AKI), that requires renal replacement therapy (RRT). Because of haemodynamic instability the safest therapeutic choice seems to be continuous veno-venous hemodiafiltration (CVVHDF). This RRT mode removes particles in the size of few daltons even up to 10 kilodaltons (kDa) such as metabolic product waste, ions, hormones etc. LMWH with average molecular weight of 4.5 kDa and fondaparinux with average molecular weight of 1.7 kDa may be removed during CVVHDF resulting in insufficient activity of anti-Xa factor thus increasing the risk of thrombotic complications in critically ill patients.

Inclusion Criteria:

• All adult Intensive Care Unit patients between 18 and 80 years old requiring treatment with CVVHDF;
• Indications for anticoagulant prophylaxis with enoxaparin 40 mg sc. once daily or fondaparinux 2.5 mg sc. once daily;
• Treatment with continuous veno-venous hemodiafiltration.

Exclusion Criteria:

• Indications for low molecular weight heparin use other than anticoagulant prophylaxis;
• Intracranial hemorrhage;
• Incident of serious bleeding within a week before admission to ICU, if not managed;
• Disseminated intravascular coagulopathy;
• Heparin induced thrombocytopenia;
• Hypersensitivity or allergic reaction to enoxaparin or fondaparinux;
• Thrombocytopenia < 50 G/L;
• Prothrombin time < 20% or INR (international normalized ratio) > 1.7;
• Use of antiplatelet drugs;
• Presence of congenital coagulopathy.