A 60 year old gentleman  on subcutaneous enoxaparin 80 mg bd for deep vein thrombosis has the following blood results. The blood sample was taken prior to the dose of enoxaparin


INR                          1.3                            0.9 TO 1.2
APTT                       38 SEC                    24 to 39
D dimer                    <0.2 mg/l                 <0.2 mg/l

Anti Xa                    1.8 IU/ml (therapeutic range 0.6 to 1.0 iu/ml)

 

List 2 likely causes of a raised Anti-Xa level in this patient?

[Click here to toggle visibility of the answers]

College Answer

a) If the patient has underlying  renal failure
b)  body weight is low / incorrect dose of enoxaparin

 

Discussion

Anti-Xa level measurements are discussed in some detail in this article from the Australian Prescriber.

However, to answer this question, one does not need to be overfamiliar wiith the methods of anti-Xa testing. The patient has had too much enoxparin, because the level is high.

The college wants to know why he has been overdosed with clexane.

Furthermore, they have done a trough level, suggesting that they were suspecting overdose (or accumulation) to begin with. Typically, when monitoring therapeutic activity, one takes an anti-Xa level about 3-4 hours after the injection is given, to measure the peak effect.

 

Why might one have abnormally high Anti-Xa at trough?

Usually, this means the enoxaparin is accumulating. Either the dose was too high, or the clearance mechanisms are inadequate to remove an otherwise sensible dose.

 

The dose was too high:

  • The weight-base dose was incorrectly calculated.
  • The drug was accidentally administered twice (a common medication error - morning clexane doses are given around the time of the nursing handover)
  • The weight-based dose was calculated correctly, and then the patient lost weight
  • The weight-based dose was calculated correctly according to the actual body weight, but the patient is morbidly obese and clexane does not distribute into fat.
  • The volume of distribution is decreased (the patient is dehydrated) - whereas the increase of Vd in pregnancy leads to subtherapeutic Anti-Xa levels in pregnancy.

 

The clearance mechanisms are inadequate:

  • The patient has severe renal failure (creatinine clearance less than 30ml/hr)
  • The patient is elderly (half-life is prolonged)

 

References

References

Barras, Michael. "Anti-Xa assays." AN INDEPENDENT REVIEW (2013): 98.

The Sanofi pamphlet for its brand of enoxaparin has a surprisingly detailed breakdown of its elimination pharmacokinetics.

Fareed, Jawed, et al. "Pharmacodynamic and pharmacokinetic properties of enoxaparin." Clinical pharmacokinetics 42.12 (2003): 1043-1057.

Friedrich, E., and A. B. Hameed. "Fluctuations in anti-factor Xa levels with therapeutic enoxaparin anticoagulation in pregnancy." Journal of Perinatology30.4 (2009): 253-257.

Bazinet, Annie, et al. "Dosage of enoxaparin among obese and renal impairment patients." Thrombosis research 116.1 (2005): 41-50.