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

Michele Skipp, Senior 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.