Low molecular weight heparins – should prophylactic doses be used in patients with renal impairment?

Emma Templeman, Medicines Information Pharmacist, South West Medicines Information and TrainingSource South West Medicines Information and TrainingPublished

This updated Medicines Q & A reviews the evidence available and considers when prophylactic doses of low molecular weight heparins can be used in patients with renal impairment.

  • Prophylactic doses of some LMWHs have been used in patients with RI, but experience is limited.
  • Caution is required when using any LMWH in patients with any degree of RI, especially severe RI.
  • The data on clinical outcomes for the use of prophylactic doses of dalteparin, enoxaparin and tinzaparin in patients with RI are limited, compared to those without RI.
  • The available data which has limitations (discussed in the text) suggests that prophylactic doses of dalteparin and tinzaparin do not accumulate in RI (defined as an increase in anti-Xa activity); while prophylactic doses of enoxaparin do accumulate. However, the correlation between anti-Xa activity and clinical outcomes, particularly bleeding is unclear.
  • The manufacturer of enoxaparin recommends that it is avoided in patients with a CrCl<15ml/min. In patients with a CrCl 15ml/min to 30ml/min they advise that the dose should not exceed 20mg daily. However, only one trial which tested the efficacy and safety of this reduced dose (where a 40mg dose would normally be indicated in the absence of RI) was identified at the time of writing. This trial had several limitations making it difficult to draw firm conclusions.
  • No specific dose adjustment is advised in RI by the manufacturers of dalteparin.
  • The manufacturers of tinzaparin state that it is not recommended in patients with severe RI (<30ml/min), as dosage in this population has not been established. When required in patients with a CrCl >20ml/min, tinzaparin can be used cautiously with anti-Xa monitoring since available evidence demonstrates no accumulation at CrCl>20ml/min
  • The manufacturers of dalteparin and enoxaparin also advise that monitoring of anti-Xa levels should be considered in patients with RI.
  • It is recognised that anti-Xa level monitoring may unavailable or difficult in some healthcare settings.
  • The current limited trial evidence suggests that prophylactic doses of:
    • tinzaparin can be used with caution without dose reduction in patients with a CrCl >20ml/min.
    • dalteparin can be used with caution without dose reduction in all levels of RI.
  • The safety of extended-duration prophylactic doses of LMWHs in RI has not been adequately studied. Most studies are based on short treatment periods (typically 4 to 10 days). Therefore, it is not clear if accumulation can occur in patients with moderate RI when LMWHs are given for extended periods. Close monitoring and measurement of anti-Xa levels may be required to rule out accumulation when LMWHs are used for extended periods in RI.
  • NICE advise that either LMWH or UFH may be used in patients with severe RI (defined as an eGFR of less than 30ml/min/1.73m2) who require pharmacological thromboprophylaxis.
  • There is limited evidence from a retrospective cohort study to suggest that using UFH instead of enoxaparin in patients with severe RI (CrCl <30ml/min) may reduce major bleeding. However, this study had several limitations discussed above which limit the reliability of its conclusions.
  • Large high quality studies are needed:
    • to evaluate whether monitoring of anti-Xa activity would improve safety in patients with RI;
    • to allow conclusions regarding accumulation to be made;
    • to compare efficacy and safety between the various LWMHs and UFH in all levels of RI.