cardiovascular
Preventing and treating VTE in patients with renal insufficiency
Patients with chronic kidney disease have an elevated risk for bleeding with declining glomerular filtration rate , even in the absence of anticoagulants , but also have an elevated risk of thromboembolism
Piet Habbel Cecilia Bozzetti Hanno Riess Department of Hematology , Oncology and Tumor Immunology , Charité University Medicine Berlin , Germany
Chronic kidney disease ( CKD ), a reduction in renal function with decreasing glomerular filtration rate ( GFR ) is increasing in incidence as well as in prevalence due to a growing elderly population . The progressive reduction in GFR to less than 60ml / min ( modest renal insufficiency ; mRI ) or severe renal insufficiency ( sRI ; with GFR < 30ml / min ) may lead to end stage renal disease ( ESRD ) with a requirement for chronic haemodialysis ( CHD ).
In parallel with progressing age , there is an increase in CKD , elective and non-elective surgeries , non-valvular atrial fibrillation ( AF ) and venous thromboembolism ( VTE ). Of note , CKD and AF as well as CKD and VTE are not independent conditions , but , in both situations , positive bidirectional relationships have been proved . 1 , 2
Patients undergoing major surgery have an elevated risk for thromboembolic events . In these patients and those suffering any VTE , anticoagulant therapy is highly effective in the primary and secondary prevention of thromboembolism . Yet , this efficacy of anticoagulant drugs also exposes patients to an increased risk of anticoagulant-associated bleeding . 3
This short review will neither address the appropriate anticoagulation in the context of CHD nor the problem of how to adapt anticoagulation in acute kidney failure , but will discuss specific aspects of anticoagulant treatment in patients with CKD at risk for acute or recurrent VTE .
19 HHE 2018 | hospitalhealthcare . com
Anticoagulant drugs and renal insufficiency For a long time parenteral drugs such as unfractionated heparin ( UFH ), low-molecularweight heparins ( LMWH ), or fondaparinux ( FPX ) were used for acute initiation of anticoagulation therapy , which was then switched to an oral vitamin K antagonist ( VKA ) such as warfarin . Nowadays direct oral anticoagulants ( DOACs ) have become available for primary and secondary prevention as recently reviewed by Moss and colleagues . 4
These anticoagulant drugs do not only differ in their mode of action and the time course of anticoagulant activity but also in the degree of drug – drug interactions as well as in the dependency of their pharmacokinetic parameters on kidney function ( Table 1 ). Most anticoagulant drugs ( LMWH , FPX , DOACs ) can accumulate in patients with impaired renal capacity . 5
The recent randomised Phase III landmark studies in VTE 6 and the supporting evidence in AF , 7 demonstrated the efficacy and safety of anticoagulant drugs but excluded patients with sRI or even ESRD . With the exception of LMWH – where some data are available 8 , 9 – recommendations on how to treat patients with markedly reduced GFR having an urgent need for anticoagulation are based mainly on considerations of pharmacokinetic data , extrapolation of clinical study results in subgroup analyses of patients with mRI , and case series .
Patients with CKD have an elevated risk for bleeding with declining GFR , even in the absence of antithrombotic drugs , 10 but also seem to have an elevated risk of thromboembolism . 2 Therefore , a thorough evaluation of the patient ’ s individual risk profile concerning thromboembolic events and bleeding complications has to be recommended prior to the choice of drug and dose for anticoagulation . Moreover , this risk profile should be re-assessed on a regular basis .
Due to different pharmacodynamic properties of anticoagulant drugs ( Table 1 ), the risk of accumulation , resulting in an increased bleeding risk , differs among the available drugs and needs to be considered in patients with an estimated GFR of < 50ml / min ( Table 2 ).
The miscellaneous LMWH have different molecular weight distributions , affecting their excretion by the kidneys , and resulting in an inverse relationship between molecular weight and renal clearance . 11 Moreover , FPX has a longer half-life and a higher risk of accumulation in