Anticoagulation with heparins in the presence of significant renal impairment is complex as both low molecular weight-heparin (LMWH) and unfractionated heparin (UFH) are likely to accumulate when the creatinine clearance falls below 30 ml/min.

There are two options:

• Use subcutaneous (SC) Dalteparin with 2/3 of the normal weight adjusted dosage (see Table 1.4 for dose banding recommendations) and monitor LMWH anti-Xa plasma levels. The advantage of this approach is that the anticoagulant response is more predictable, but the disadvantage is that initially monitoring is still required and LMWH is only partially reversible in the event of bleeding. This approach is not appropriate in the peri-operative setting. (Note: Tinzaparin has a longer chain length and is more easily eliminated in renal impairment than Dalteparin: however Tinzaparin is only approved on the LJF for specialist use only by the haemodialysis unit. If used this would be non-formulary. A small supply of Tinzaparin is kept in stock in pharmacy and can be used in the setting of renal impairment, but please note that LMWH-anti-Xa levels are still necessary).

• Use intravenous (IV) UFH and monitor the APTT appropriately. Advantages of this approach are that the UFH can be easily stopped if necessary and its effects wear off rapidly. It can also be easily reversed with protamine. The disadvantage is that achieving adequate anticoagulation is unpredictable and dosage adjustments based on appropriately timed APTT measurements require careful management. In patients with significant renal impairment, this approach should be used in patients in the peri-operative period.

LMWH anti-Xa levels are ordered on TRAK as "heparin assay" and click on LMWH; samples are sent in a green citrated tube filled adequately to the level marked on the tube. Samples must be couriered to the RIE haematology laboratory if the patient is being managed at other NHS Lothian sites. A 24-hour service is available for this automated test and all requests should be discussed with the duty laboratory haematology biomedical scientist (laboratory): extension 26093 or page 6550/via switchboard out of hours.

A peak LMWH anti-Xa level should be taken after the first or second dose of the LMWH have been administered if being given as a single daily dose, and taken at 3-4 hours following the administration of the drug. If the LMWH is being given twice daily, then check the LMWH anti-Xa level after the third dose of LMWH.

Interpretation:

For patients on once daily dosing, the expected peak plasma concentration is about 1.0 anti-Xa unit per mL with a range of 0.5 to 1.5 (and 0.5 to 1.0 anti-Xa units per ml for twice daily dosing). The duty haematologist can assist with dose adjustment if the level is subtherapeutic, low or supratherapeutic.

*The use of CrCl is preferred over eGFR in obese patients with renal impairment. Creatinine clearance could be calculated by using the CrCl calculator on the Intranet (see link below).

http://intranet.lothian.scot.nhs.uk/Pages/Search-Results.aspx?k=creatinine%20clearance%20calculator

**Graduated syringes containing 10,000 units in 1mL of Dalteparin are kept at RIE pharmacy and are available to administer these doses.