**2.3 Treatment of venous thromboembolism in chronic renal disease patients**

Anticoagulants are widely used to prevent and treat venous thromboembolism, these drugs are often used in patients with renal impairment. Renal impairment is at the same time, a risk factor for bleeding and thrombosis during anticoagulant therapy and may influence the balance between the safety and efficacy of such drugs (Harder, 2011).

The available anticoagulants for the treatment of thromboembolism are heparins, the Factor X inhibitor fondaparinux, warfarin and the new anticoagulants Factor X inhibitors and direct thrombin inhibitors. Most of the antithrombotics are eliminated primarily by the kidneys , so dosing in patients with several renal impairment may require dosage reduction or increase frequency of monitoring for bleeding and thromboembolism complications or both(Lobo, 2007).

Venous Thromboembolism in Neonates, Children and

**2.3.1.3 Fondaparinux** 

anticoagulant activity [Hirsh,2008]

**2.3.2 Vitamin K antagonists** 

used around the world.

**2.3.3.1 Dabigatran etexilate** 

activity in patients with renal failure should be considered.

Patients with Chronic Renal Disease – Special Considerations 47

venous thromboembolism. For tinzaparin and dalteparin monitoring of anticoagulant

Fondaparinux is a synthetic pentasaccharide, that inhibits factor Xa by binding to antithrombin. After subcutaneous administration the peak plasma concentration is achieved within 2 hours, the half life is 17 hours in young healthy subjects and 21 hours in the elderly.

However the ACCP guidelines for VTE prevention do not recommend specific doses adjustments for fondaparinux in renal impaired patients, depending of the circumstances the guidelines recommended avoiding the anticoagulant, lowering dose or monitoring

The summary of manufacturers insert states contraindicated of fondaparinux in patients with severe renal impairment (clearance of creatinine ‹20 ml/min) and use with caution in patients

Vitamin K antagonist inhibit the hepatic synthesis of factors II, VII, IX and X and protein C and S. There are various vitamina K antagonists, however, warfarin is the most commonly

After oral administration warfarin is rapidly absorbed reaching the plasma peak concentration within 90 minutes, the peak therapeutic effect is acquired at 36 hours. Warfarin undergoes oxidative metabolism via the CYP450 system in the liver and less than

The risk of bleeding and thromboembolic complications is increased when using warfarin in the chronic kidney disease population and depends of the INR target, incidence of values outside of the target or other comorbid conditions. Warfarin dosing requirements tend to be lower as renal function declines. (Limdi , 2009) Concurrent drug interactions and acute medical problems such as heart failure or infections can influence the dose response to warfarin. Because the complexity of managing warfarin and increased risk of adverse outcomes in the chronic kidney disease setting, warfarin management in those patients

Dabigatran etexilate is a direct thrombin inhibitor, currently approved for the prevention of venous thromboembolism in orthopedic surgery patients. After oral administration peak plasma concentrations are achieved within 2 hours of administration. Elimination of dabigatran is predominantly via the renal pathway, 80% of the administered dose is excreted unchanged in the urine within the first 24 hours after an intravenous dose and is

Limited data are avalaible on dabigatran pharmacokinetics in patients with renal

should be referred when possible to dedicated anticoagulant services.(Dager ,2003).

with moderate renal impairment (creatinine clearance 30 a 50 ml/min)[ Harder 2011]

1% of the drug is excreted unchanged in the urine. (Ansell, 2008)

**2.3.3 Novel oral anticoagulants in patiens with renal disease** 

contraindicated in patients with severe renal impairment (Stangier, 2008)

impairment for venous thromboembolism treatment.(Dahl, 2009)

Up to 80% of fondaparinux is eliminated as unchanged drug via the kidneys.

Decisions for anticoagulation therapy respect the agent selected, dose, duration of treatment, and approaches to monitoring should balance the risks between bleeding and thrombosis.
