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
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