Heparin Dose Adjustment in the presence of Renal Impairment (157)

Heparin and heparin-like anticoagulants (unfractionated heparin (UFH), low molecular weight heparins (LMWH) and the pentasaccharide, fondaparinux) vary considerably in their glycosaminoglycan composition, specifically their average chain size (UFH > LMWH > fondaparinux). Even within the LMWH group there can be subtle differences in average chain size (tinzaparin > dalteparin > enoxaparin). These differences have important effects both on the antithrombin-mediated target specificity and dependence on renal clearance – smaller heparins having a higher anti-factor Xa: anti-factor IIa ratio and a greater dependence on renal clearance. The latter is very relevant when prescribing these agents, either at prophylactic or therapeutic doses, for patients with substantially reduced kidney function (CrCl<30mL/min) as observational data demonstrate clinically important increase in bleeding complications of anticoagulation in this group of patients. For this reason, in-patients in the NHS GGC renal unit with chronic kidney disease and CrCl <30mL/min do not routinely receive pharmaceutical thromboprophylaxis when admitted for non-operative reasons unless there are other risk factors for thrombosis.

Within NHS GGC the heparin agent of choice may vary between treatment and prophylaxis and for different indications – please consult NHS GGC Formulary or Therapeutics Handbook for preferred agent of choice. Based on relevant SPC guidance and limited additional literature the following recommendations are offered.

Note that this guideline is for adult non-pregnant patients only.

For dose adjustments in adult patients with very low or very high body weight, refer to GGC guideline on Staffnet – Clinical Guideline Repository
	CrCl (ml/min) GGC CrCl calculator available here
	≥ 30 ml/min	< 30 ml/min
Enoxaparin	40mg once daily	20mg once daily* if CrCl 30-15 ml/min AVOID if CrCl < 15 ml/min Use an alternative LMWH
Dalteparin	5,000 units once daily	5,000 units once daily* if CrCl 30-15 ml/min 2,500 units once daily* if CrCl < 15 ml/min
Tinzaparin	3,500 / 4,500 units once daily* as per indication AVOID if CrCl < 20ml/min, use an alternative LMWH
Fondaparinux	2.5 mg once daily if CrCl > 50 ml/min 1.5 mg once daily if CrCl 50-20 ml/min AVOID if CrCl < 20 ml/min, use a suitable LMWH

*If CrCl < 30ml/min and prophylactic LMWH treatment has continued for ≥10 days, re-assess anti-Xa activity after 10th dose of LMWH, to ensure there has been no significant drug accumulation (target 4h peak level: 0.1 - 0.4 units/ml)

If a patient with a CrCl < 20 ml/min on a therapeutic LMWH regimen, which cannot be omitted for 36-48h, is scheduled for an invasive procedure (including small procedures such as a biopsy or central line insertion) it is recommended that the patient is switched to an UFH regimen prior to the procedure as follows:

• IV UFH is started 20-24h after the last dose of therapeutic LMWH
• IV UFH is stopped 6h prior to the procedure
• IV UFH is restarted, assuming adequate haemostasis, 4-6h post procedure

There are different concentrations of UFH currently available – only the 1000 units/ml preparation should be used at all times to reduce the risk of dose errors and serious clinical incidents.

If you require further advice consult Therapeutics Handbook or contact haematology.

For dose adjustments in adult patients with very low or very high body weight, refer to GGC guideline on Staffnet – Clinical Guideline Repository
	CrCl (ml/min) GGC CrCl calculator available here
	≥ 30 ml/min	30-10 ml/min	< 10 ml/min
Dalteparin (weight-banded dosing)	200 units/kg once daily [max 18,000 units] Consider dalteparin 100units/Kg twice daily in patients with high bleeding risk	200 units/kg once daily* [max 18,000 units] Consider dalteparin 100units/Kg twice daily in patients with high bleeding risk	Due to lack of evidence suggest use of UFH#        See section below: "Use of Heparin During Haemodialysis Procedures', for recommendations for anticoagulation prescribing during haemodialysis         #In the Renal Unit enoxaparin 1mg/kg once daily is regarded as an acceptable alternative
Enoxaparin (weight-banded dosing)	VTE: 1.5 mg/kg once daily Consider enoxaparin 1mg/Kg twice daily in patients with high bleeding risk or patients perceived to be at high risk of recurrent VTE ACS: 1 mg/kg twice daily	VTE: 1 mg/kg once daily* AVOID if CrCl < 15 ml/min Use an alternative LMWH ACS: 1mg/kg once daily* (remains treatment of choice if CrCl < 15 ml/min)
Tinzaparin	175 units/kg once daily	175 units/kg once daily* AVOID if CrCl < 20 ml/min Use an alternative LMWH
Fondaparinux	SVT: 2.5 mg once daily if CrCl > 50 (1.5 mg if CrCl 20-50 ml/min) ACS: 2.5mg once daily if CrCl ≥20ml/min AVOID if CrCl <20 ml/min, use a suitable LMWH
Unfractionated heparin (UFH) (intravenous Na Heparin)	**Use 1000 units/ml preparation at all times** Loading IV dose: 5,000 units, if appropriate Maintenance IV infusion: start at 18 units/kg/h, check APTT ratio 6 hours after commencement of infusion, and 4 hours after any change in infusion rate, then daily (target APTT ration: 1.8-2.6)

VTE: venous thrombosis; SVT: superficial vein thrombosis; ACS: acute coronary syndrome; UFH: unfractionated heparin

*If CrCl < 30 ml/min consider assessing anti-Xa activity after 3rd dose (to confirm therapeutic levels have been achieved) and after 8-10th dose to ensure there has been no significant drug accumulation (target 4h peak level: 0.5 – 1.2 units/ml)

 

If not on regular anticoagulation for other indications, haemodialysis patients should be considered for anticoagulation for the prevention of clotting of the extracorporeal circuit.

Within NHS GGC the LMWH of choice for use during haemodialysis is subject to regular review. Please seek advice from renal team before prescribing.

Tinzaparin dose regimen:

Tinzaparin 2,500 units, if dialysis ≤ 4h
Tinzaparin 3,500 units, if dialysis > 4h, or circuit clotting on 2,500 units

Dalteparin dose regimen:

If dry weight ≤ 60Kg 2,500 units
If dry weight > 60Kg 5,000 units

Please note that dalteparin dose is not dependent on duration of dialysis.

 

When LMWH is used for haemodialysis anticoagulation, routine monitoring of anti-Xa activity is not required.