HHE Cardiovascular supplement 2018 - Page 20

Table 1 Characteristics of anticoagulant drugs UFH LMWH FPX VKA (warfarin) Mechanism AT-dependant AT-dependant AT-dependant Inhibition of γ-Carboxylase Anticoagulant principle Indirect Indirect Indirect Indirect Renal clearance Low 30–60% 65–100% 1% Application iv, sc sc po po T max AE 0 h iv, 2–4h 3–4h 1–2h ≈3d T ½ AE 1-2h (iv) 3–4h (sc) 4-8h 17–21h 2–4d Potential for Low Low None Very high interactions Table 2 Dosing of anticoagulant drugs in CKD Creatinin clearance UFH LMWH FPX VKA (Warfarin) VTE – PREVENTION > 60ml/min Regular dosage Monitor INR 1.5–2.0 60 /min Reduced dosage 30 ml/min (1.5mg/d) Reduced dosage* 15 ml/min Not recommended Not recommended < 15ml/min VTE – TREATMENT > 60ml/min Regular dosage Monitor INR 2.0–3.0 Monitor aPTT or anti-Xa 60 ml/min 30 ml/min Contra-indicated 15 ml/min Reduced dosage*° < 15ml/min Not recommended * Consider monitoring anti-factor-Xa-activity, # consider monitoring anti-factor-IIa-activity; ° brand-specific dose adaptations. Approved dose-recommendations not based on prospective comparative data. Dose suggestions based on very small data sets Primary prevention of VTE in CKD patients undergoing surgery Perioperative morbidity and mortality are common issues in the management of patients with kidney diseases undergoing elective or emergency surgery. Many of these patients are to be initiated on postoperative anticoagulation for VTE prevention. Pharmacological thromboprophylaxis reduces the risk of VTE, most convincingly demonstrated after elective total hip or knee replacement surgery. For patients undergoing these procedures, randomised clinical trials and meta-analysis of DOACs demonstrate an overall comparable efficacy and safety for DOACs compared to LMWH. 14 As long as GFR is >30ml/min, standard dosages of LMWH or most DOACs can safely be applied postoperatively for 10 to 35 days. Concerning FPX, a reduced dosage of 1.5mg once daily is recommended for patients with a limited GFR between 50 and 20ml/min. For patients with sRI standard doses of LMWH may be safe, but convincing prospective study data are missing. 8 Dose reductions by 30–50% and/or monitoring of the anti-factor-Xa activity are suggested in patients with GFR between 30 and 15ml/min. The subcutaneous application of 3 x 5000IU or 2 x 7500IU UFH per day is a traditional and effective procedure in patients with sRI or ERD. patients with CKD compared with LMWH. For DOACs, the thrombin inhibitor dabigatran has the highest risk of accumulation in patients with impaired GFR, whereas the oral factor Xa inhibitors have a lower risk for accumulation. 7 For UFH and VKA, the risk of accumulation is very low, but therapeutic anticoagulation demands for laboratory controls – via aPTT or anti-factor Xa activity for UFH and via INR for VKA – thus minimising the risk of unintended over-anticoagulation. Monitoring of the anticoagulant activity of LMWH, FPX or DOACs are not regularly recommended but available. Life-threatening complications such as heparin-induced thrombocytopenia type II and warfarin-induced purpura fulminans do rarely occur and their incidences do not seem to be influenced relevantly by CKD. Warfarin-related nephropathy is another seldom complication, which may stimulate the progression of CKD, especially when the INR is above therapeutic range. Interestingly, a dabigatran-related nephropathy has recently been reported. 12 Yet, reports also indicate calciphylaxis related to the use of warfarin in patients with CKD. 13 Thus, VKA in patients suffering from CKD is controversially discussed among nephrologists, unless there is an absolute indication, such as after artificial heart valve replacement. 13 20 HHE 2018 | hospitalhealthcare.com